to view the Scientific Program

Transcription

Annual Conference of the
Canadian Blood and Marrow Transplant Group
June 11 to 14, 2014 • The Westin Nova Scotian • 1181 Hollis Street • Halifax, NS
Scientific Program
In conjunction with the Canadian National Transplant Research Program, Canadian Apheresis Group,
Canadian Hematology Society, and Venous Thrombosis Clinical Trials Organization
CBMTG Head Office • Malachite Management Inc • 375 West 5th Avenue Suite 201, Vancouver BC Canada V5Y 1J6
T. 604.874.4944 F. 604.874.4378 Email: [email protected] Web: www.cbmtg.org
Annual Conference of the Canadian Blood
and Marrow Transplant Group
June 11 to 14, 2014 • The Westin Nova Scotian • Halifax, NS
A Message from the Premier of Nova Scotia
On behalf of the province, Minister of Health and Wellness Leo Glavine and I are pleased to welcome physicians, nurses and nurse practitioners,
lab technologists, program coordinators, and pharmacists from across Canada to the Canadian Blood and Marrow Transplant Group national
annual conference in Halifax.
It is dedicated professionals like yourselves who continue to give hope, care and comfort to Canadians suffering with blood and marrow diseases.
I know that recipients who are battling this disease, their families, and the families of donors are grateful for your expertise, your compassion and
your dedication.
I also want to welcome all the volunteers, organizers and sponsors to Nova Scotia. Without your hard work, this conference would not be possible.
We wish you a successful conference and hope you will continue your work to make Canada the best place in the world to have a blood and
marrow transplant.
Regards,
Honourable Stephen McNeil, M.L.A.
Premier
A Message from the Mayor of Halifax
As Mayor of Halifax Regional Municipality it is my distinct pleasure to extend warm greetings and a special welcome to all attending the Canadian
Blood and Marrow Transplant Group Annual Conference.
Halifax Regional Municipality is the place to be with its dynamic and intriguing mix of heritage and culture. A marquee destination embracing a
diversity of people, communities, shops, restaurants, and nightlife, our city will present you with a truly original experience.
Our culturally rich and historic port city has been entertaining guests for over 250 years and we take pride in our reputation as one of the world’s
most hospitable and welcoming destinations.
I want to acknowledge, with gratitude, the Conference Planning Committee, led by Dr. Stephen Couban, Director of the Blood and Marrow
Transplant Program at QEII Health Sciences Centre, and the rest of the Halifax Blood and Marrow Transplant Team for hosting this event here in
our region and for their hard work creating an exciting program and great educational experience for all delegates.
I wish you much success and trust your visit will be a truly memorable experience.
Kindest regards,
Mike Savage
Mayor
2
CBMTG Head Office 375 West 5th Avenue, Suite 201, Vancouver, BC V5Y 1J6
T: 604-874-4944 • F: 604-874-4378 • E: [email protected] • W: www.cbmtg.org
Table of Contents
Welcome Message....................................................................................................................................4
Board of Directors and Conference Planning Committee.............................................................................5
Accreditation.............................................................................................................................................5
Disclosures................................................................................................................................................6
Invited Speakers, Chairs, and Panelists.......................................................................................................7
Partners....................................................................................................................................................8
Conference-at-a-Glance.............................................................................................................................9
CBMTG Committee and Special Interest Group Meetings..........................................................................13
CBMTG Session Summaries......................................................................................................................14
CNTRP Session Summaries.......................................................................................................................20
CAG/CAAN/CHS Conference-at-a-Glance..................................................................................................21
Oral Abstracts Index................................................................................................................................23
Oral Abstract Summaries.........................................................................................................................23
Poster Abstract Index..............................................................................................................................28
Poster Abstract Summaries......................................................................................................................31
Non-Presenting Abstracts Index...............................................................................................................31
Westin Nova Scotian Floor Plan...............................................................................................................62
Social Event Information..........................................................................................................................63
About CBMTG.........................................................................................................................................63
3
A Message from the CBMTG President
Dear colleagues,
On behalf of the executive and board I am pleased to welcome you to our annual conference of the Canadian Blood and Marrow Transplant Group
(CBMTG). We hope that you will find many opportunities to learn and network.
This conference would not be possible without the leadership of Dr. Stephen Couban and the conference planning committee, whose work and
dedication resulted in the strong scientific program that we are proud to present. Furthermore, we wish to thank the Canadian Apheresis Group
(CAG), the Canadian National Transplant Research Program (CNTRP), the Canadian Hematology Society (CHS), and the Venous Thrombosis Clinical
Trials Organization (VECTOR), all of whom will be hosting joint sessions with us. We do hope these joint sessions will be the foundation for
knowledge exchange and a fertile ground for collaboration.
We wish to invite you to attend the annual general meeting of the organization scheduled for Friday, June 13 from 6 to 7 p.m. There you will learn of
the work that is being done on your behalf. It was a busy year and the executive will be presenting the CBMTG strategic plan for the next five years.
We hope that this conference will support and inspire your practice.
Sincerely,
Silvy Lachance, MD, FRCPC, CSPQ
President
A Message from the Conference Chair
Dear friends and colleagues,
On behalf of the Canadian Blood and Marrow Transplant Group conference planning committee and the Halifax BMT team, welcome to Halifax!
We are very excited to be hosting the 2014 CBMTG Annual Conference and have worked hard to create an interesting and informative academic
program for you.
The conference planning committee enjoyed the challenge of creating a program that would appeal to the broad range of BMT professionals
across Canada and provide information on the latest trends and discoveries in BMT from around the world. We are very fortunate to have both
national and international speakers here to share their expertise with us, and we hope that each delegate finds this conference to be a valuable
learning and networking opportunity.
For the first time in a number of years, a number of groups with interests in hematology are meeting in Halifax at the same time as the annual
CBMTG meeting. We are happy to welcome the Canadian Apheresis Group (CAG), the Canadian National Transplant Research Program (CNTRP),
the Canadian Hematology Society (CHS), and the Venous Thrombosis Clinical Trials Organization (VECTOR), all of whom will be hosting joint
sessions with the CBMTG and/or society meetings here in Halifax.
We hope that you get the chance to spend some time in our beautiful city! We are known for a beautiful harbor, fantastic live music, and delicious
lobster– all three of which you will experience at the conference social event on Saturday night!
Sincerely,
Stephen Couban, MD, FRCPC
Conference Chair
4
Board of Directors
President,
Silvy Lanchance,
MD, FRCPC, CSPQ
Past President,
Ronan Foley,
MD, FRCPC
President-Elect,
Christopher Bredeson,
MD, MSc, FRCPC
Treasurer,
Andrew Daly,
MDCM, FRCPC
Secretary,
Jennifer Wiernikowski,
MN, NP-Adult, CON(C)
Director-at-large,
Research
Donna Wall,
MD
Director-at-large,
Education
Naheed Alam,
MD
Conference Planning Committee
Chair:
Stephen Couban, MD, FRCPC
Committee Members:
Imran Ahmad, MD
Christopher Bredeson, MD
Sherri Briggs, RN
Raewyn Broady, MD
Jo-Ann Edwards, NP
Conrad Fernandez, MD, FRCPC
Angeline Giftakis, MLT
Lora Jay Gray, BScPharm
Wanda Hasegawa, MD
Joanne Hickey, MD, FRCPC
Gertrude Kells, RN
Andrea Kew, MD
John Kuruvilla, MD
Kylie Lepic, MD
Brenda Letcher, MLT
Joan Macleod
David Mitchell, MD, FRCPC
Gizelle Popradi, MD, FRCPC
Tracy Robinson, RN
Matthew Seftel, MD, MPH, MRCP, FRCPC
Lynn Savoie, MD
Marie Tulloch, MLT
Darrell White, MD
Accreditation
As an accredited provider, Dalhousie University, CME, designates this continuing medical education activity for up to 14.50 credit hours as
an accredited group learning Section 1 activity as defined by the Maintenance of Certification Program of the Royal College of Physicians and
Surgeons of Canada.
In keeping with CMA Guidelines, program content and selection of speakers are the responsibility of the planning committee. Support is directed
toward the costs of the course and not to individual speakers.
Participants should only claim credit for the actual number of hours attended. To receive your certificate of attendance please complete the online
or paper version of the CBMTG 2014 conference evaluation.
5
Disclosures
Please note the following disclosures have been submitted:
Imran Ahmad, Planning Committee Member
Consultant – Celgene
Danièle Marceau, Speaker
Research Support – Alexion
Andrew Artz, Speaker
Research Support – Miltenyi Biotec
Philip L. Mccarthy, Speaker
Consultant – Celgene, Janssen, Millenium
Philippe Bouchard, Speaker
Consultant – Merck
John Miller, Speaker
Employee – National Marrow Donor Program, Minneapolis, Mn
Christopher Bredeson, Planning Committee Member
Research Support – Celgene, Sanofi, Otsuka
Other Financial Support – Celgene, Sanofi, Merck, Otsuka
Gizelle Popradi, Planning Committee Member
Research Support – Merck
Consultant – Novartis, Bristol–Myers Squibb, Merck, Pfizer,
Hoffman–La Roche, Janssen, Celgene
Marc Carrier, Speaker
Research Support – Leo Pharma, Bristol–Myers Squibb
Consultant – Pfizer, Bayer
Stephen Couban, Planning Committee Member
Research Support – Novartis, Bristol–Myers Squibb, Sanofi
Other Financial Support – Novartis, Lundbeck, Bristol–Myers
Squibb, Pfizer, Seattle Genetics, Hoffman–La Roche, Sanofi
Ad Board/ Financial Interest– Novartis, Lundbeck, Bristol–Myers
Squibb, Pfizer, Seattle Genetics, Hoffman–La Roche, Sanofi
Michael Crump, Speaker
Research Support – Hoffman–La Roche
Consultant – Seattle Genetics, Genentech
Joanne Hickey, Planning Committee Member
Research Support – Amgen, Celgene, Onyx, Gilliad, Alexion
Lina Ho, Speaker
Consultant – Pfizer
Atul Humar, Speaker
Grant Support – Hoffman–La Roche,
Honoraria – Astellas, Chimerix
Andrea Kew, Planning Committee Member
Research Support – Celgene, Glaxo Smith Kline, Sunesis
Other Financial Support – Celgene, Pfizer, Novartis,
Lundbeck
Lynn Savoie, Planning Committee Member
Research Support – Novartis, Bristol–Myers Squibb, Celgene,
Karyopharm
Kirk Schultz, Speaker
Consultant – Healthcord Cord Blood Bank, Bristol–Myers Squibb,
SBIBiotech
Research Support – Sanofi, Novartis, Medac, Medimmune
Other Financial Support – USA Pharma, Medac, Healthcord Cord
Blood Bank
Matthew Seftel, Speaker, Planning Committee Member
Consultant – Kiadis
Other Financial Support – Lundbeck, Otsuka, Pfizer
Sudeep Shivakumar, Speaker
Research Support – Bayer, Pfizer
Consultant – Bayer, Boehringer Ingelheim, Pfizer, Leo Pharma
Leigh Sims Poston, Speaker
Advisory Group Member – Iccba
Daniel Weisdorf, Speaker
Research Support – Miltenyi Biotec
Consultant – Amgen, Pharmacyclics
Neal Young, Speaker
Research Support – Glaxo Smith Kline
Richard Larson, Speaker
Research Support – Amgen, Ambit, Astellas, Exytech, Ariad,
Novartis
Consultant – Ariad, Bristol–Myers Squibb, Celgene, CVS
Caremark, Novartis, Pfizer, Sanofi
6
Invited Speakers, Chairs, and Panelists
Muneer Abidi, MD, Wayne State University, Karmanos Cancer Center, Detroit, MI, USA
Silvy Lachance, MD, FRCPC, CSPQ, Hôpital Maisonneuve-Rosemont, Montreal,
Imran Ahmad, MD, Hôpital Maisonneuve-Rosemont, Montreal, PQ, Canada
Upton Allen, MBBS, MSc, FAAP, FRCPC, The Hospital for Sick Children, Toronto,
Richard A. Larson, MD, University of Chicago, Chicago, IL, USA
Kylie Lepic, MD, McMaster University/ Juravinski Hospital and Cancer Centre,
ON, Canada
PQ, Canada
Andrew Artz, MD, MS, University of Chicago Medicine, Chicago, IL, USA
Peter Bader, MD, Hospital for Children and Adolescents, Frankfurt, Germany
Wing Leung, MD, PhD, St. Jude Children’s Research Hospital, Memphis, TN, USA
Christopher Bredeson, MD, MS, FRCPC, The Ottawa Hospital, Ottawa, ON, Canada
David Maginley, M. Div., Nova Scotia Cancer Centre, Halifax, NS, Canada
Philippe Bouchard, BPharm, MSc, BCOP, Hôpital Maisonneuve-Rosemont,
Danièle Marceau, MD, CHU de Quebec, Quebec, PQ, Canada
Samantha Mayo, University of Toronto, Toronto, ON, Canada
Montreal, PQ, Canada
Geoffrey Browne, Stemsoft Software Inc., Vancouver, BC, Canada
Giovanna Cameron, BMT/Leukemia Program of BC, Vancouver, BC, Canada
Marc Carrier, MD, MSc, FRCPC, University of Ottawa, Ottawa, ON, Canada
Hamilton, ON, Canada
Philip L. McCarthy, MD, Roswell Park Cancer Center, Buffalo, NY, USA
John Miller, MD, PhD, Donor Medical Services, National Marrow Donor Program,
Minneapolis, MN, USA
Stephen Couban, MD, FRCPC, QEII Health Sciences Centre, Halifax, NS, Canada
David Mitchell, MD, FRCPC, The Montreal Children’s Hospital, Montreal, PQ, Canada
Michael Crump, MD FRCPC, Princess Margaret Hospital, Toronto, ON, Canada
Craig Moskowitz, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Jean-Sébastien Delisle, MD, PhD, Hôpital Maisonneuve-Rosemont, Montreal,
Kristjan Paulson, MD, University of Manitoba, Winnipeg, MB, Canada
PQ, Canada
Pat Distler, MS, MT(ASCP)SBB, ICCBBA, San Bernadino, CA, USA
Jo-Ann Edwards, NP, QEII Health Sciences Centre, Halifax, NS, Canada
Conrad Fernandez, MD, FRCPC, IWK Health Centre, Halifax, NS, Canada
Angeline Giftakis, MLT, Cell Therapy Lab, CancerCare Manitoba, Winnipeg, MB, Canada
Mindy Goldman, MD, FRCPC, Canadian Blood Services, Ottawa, ON, Canada
Wanda Hasegawa, MD, Provincial Stem Cell Transplant Program,
Dalhousie University, Halifax, NS, Canada
Lina Ho, BScPhm, RPh, ACPR, Princess Margaret Hospital, Toronto, ON, Canada
Marie-Josée Hébert, MD, FRCPC, Co-Director, Canadian National Transplant
Research Program (CNTRP), Montreal, PQ, Canada
Joanne Hickey, MD, FRCPC, Memorial University of Newfoundland, St. John’s,
NL, Canada
Steven Paraskevas, MD, PhD, McGill University, Montreal, PQ, Canada
Gizelle Popradi, MD, FRCPC, Royal Victoria Hospital, Montreal, PQ, Canada
Mary Lou Robertson, BA, BSW, RSW, Capital Health Cancer Care Program,
Halifax, NS, Canada
Lynn Savoie, MD, University of Calgary/Tom Baker Cancer Centre, Calgary, AB, Canada
Matthew Seftel, MD, MPH, MRCP, FRCPC, Princess Margaret Hospital, Toronto,
ON, Canada
Kirk Schultz, MD, BC Children’s Hospital, Vancouver, BC, Canada
Christy Simpson, PhD, Dalhousie University, Halifax, NS, Canada
Leigh Sims-Poston, BS, MT(ASCP), Chester, VA, USA
Sudeep Shivakumar, MD, FRCPC, Dalhousie University/QEII Health Sciences Centre,
Halifax, NS, Canada
Atul Humar, MD, FRCPC, University of Toronto, Toronto, ON, Canada
Marie Tulloch, MLT, Cancer Care Manitoba, Winnipeg, MB, Canada
Gertrude Kells, RN, QEII Health Sciences Centre, Halifax, NS, Canada
Donna Wall, MD, Cancer Care Manitoba, Winnipeg, MB, Canada
Andrea Kew, MD, Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada
Daniel Weisdorf, MD, University of Minnesota, Minneapolis, MN, USA
Joanne Kurtzberg, MD, Robertson Clinical and Translational Cell Therapy Program,
Lori West, MD, PhD, Director, Canadian National Transplant Research Program
Durham, NC, USA
John Kuruvilla, MD, Princess Margaret Hospital, Toronto, ON, Canada
(CNTRP), Edmonton, AB, Canada
Neal Young, MD, NIH, National Heart, Lung, and Blood Institute, Bethesda, MD, USA
7
Partners
For 2014 CBMTG has led the partnership between a number of Canadian hematology and transplant associations who will be hosting sessions at
this conference. Please see a description of the associations below.
Canadian Blood and Marrow Transplant Group (CBMTG)
The Canadian Blood and Marrow Transplant Group is a national, voluntary, and multi-disciplinary organization providing leadership and promoting
excellence in patient care, research, and education in the field of blood and marrow transplant (BMT). The organization leads education and
research across the Canadian BMT field. CBMTG holds an annual conference, organizes free webinars for its members, has a robust clinical trials
program and has led the development of the national BMT registry.
The conference planning committee, led by Dr. Stephen Couban, has created a scientific program highlighting presentations on topics of interest in
the field of BMT. This program was designed for a multidisciplinary audience and topics were chosen with care. CBMTG sessions will be organized
from Thursday, June 12 to Saturday, June 14, 2014.
Canadian National Transplant Research Program (CNTRP)
The Canadian National Transplant Research Program (CNTRP) is a national initiative designed to increase organ and tissue donation in Canada
and enhance the survival and quality of life of Canadians who receive transplants.
The program is led by Drs. Lori West at the Alberta Transplant Institute at the University of Alberta in Edmonton and Marie Josée Hébert at the
Université de Montréal and brings together 116 investigators at 21 institutions from across Canada to carry out research and develop resources to
help Canadians waiting for a tissue or organ transplant.
The Society will host sessions Tuesday, June 10 to Thursday, June 12, 2014.
Canadian Apheresis Group (CAG)
The Canadian Apheresis Group was formed in 1980. The group includes representatives from approximately 40 apheresis units in 19 major
medical centres in Canada.
At the annual meeting of the CAG we focus on new evidence and techniques for plasma exchange, and also carry out a centre-by-centre
review.
The Society will host sessions Friday, June 13 to Sunday, June 15, 2014.
Canadian Hematology Society (CHS)
The Canadian Hematology Society represents all physicians and scientists with an interest in the discipline in Canada. At present there are over
280 members.
The Society will host a combined session with the CBMTG on Friday, June 13, 2014.
Venous Thrombosis Clinical Trials Organization (VECTOR)
VECTOR is a collaborative group of thrombosis physicians from various cities in Canada (Ottawa, Montreal, Halifax, Hamilton, Saskatoon, and
London) who discuss current and new research ideas in the area of thrombosis. The VECTOR members are expected to help with progress of multicentre academic projects awarded to individual group members. The executive meets via teleconference on a monthly basis to discuss the group’s
operations and face-to-face up to four times a year (rotating facility hosting the meeting).
The Society will host a combined session with the CBMTG on Friday, June 13, 2014.
CBMTG • Canadian Bone and
Marrow Transplant Group
8
CNTRP • Canadian National
Transplant Research Program
CAG • Canadian
Apheresis Society
Canadian
Hematology Society
Conference-at-a-Glance
Tuesday, June 10, 2014
12:00pm – 5:00pm
Canadian National Transplant Research Program Meetings
Commonwealth Ballroom
Wednesday, June 11, 2014
9:00am – 5:00pm
Canadian National Transplant Research Program Meetings Main Session located in Harbour AB, Breakout Rooms TBD
4:00pm – 7:00pm
Conference Registration
Coat Check
4:00pm – 8:00pm
Speaker Services
Northumberland Room
See page 20 for more details.
Thursday, June 12, 2014
7:00am – 7:00pm
Coat Check
7:00am – 4:00pm
Speaker Services
Northumberland Room
Session 1: CBMTG-CNTRP Joint Session
Facing a common enemy, viral infections in SOT and AHCT
Chair: Marie-Josée Hébert, MD, FRCPC
Coffee and pastries will be provided.
8:00am – 11:00am
8:00am Welcome by the CBMTG and CNTRP: Building bridges between the SOT and BMT scientists – where we are
after 1 year
Silvy Lachance, MD, FRCPC, CSPQ, Marie-Josée Hébert, MD, FRCPC
8:40am Viral infections: From bench to beside
Atul Humar, MD, FRCPC
9:10am Risk prediction tools based on viral-host interactions that predispose young SOT and HSCT patients to EBV
Upton Allen, MBBS, MSc, FAAP, FRCPC
9:40am Adoptive T-cell immunotherapy to treat and prevent virus-related complications post-transplantation
Jean-Sébastien Delisle, MD, PhD
10:20am – 10:30am Health Break in the Atlantic Ballroom
10:30am Interactive session: Engaging the HSCT and SOT communities within the CNTRP
Steven Paraskevas, MD, PhD, Lori West, MD, PHD, Kirk Schultz, MD
10:20am – 10:30am
Health Break
Atlantic Ballroom
11:00am – 1:00pm
Symposium #1: Lunch
Session 2A: Clinical Trials
Network Meeting
Session 2B: Multidisciplinary Allied Health Session 2C: Laboratory
Maritime Room
Technologists
Harbour Suite AB
Chairs: Jo-Ann Edwards, NP,
Gertrude Kells, RN
Chair: Donna Wall, MD
1:00pm – 4:00pm
Lunenburg Room
Chairs: Angeline Giftakis, MLT,
Giovanna Cameron
Access to high cost treatments: Navigating
the complex world of oncology drug coverage ISBT 128: From a global picture to
Mary Lou Robertson, BA, BSW, RSW
the details
Near Death Experiences: Hope, Hypoxia,
Pat Distler, MS, MT(ASCP)SBB
and Hypothesis
ISBT 128 product code selection:
David Maginley, M. Div
Which codes do I want? Which codes
Aprepitant in blood and marrow
do I need?
transplantation: To add or not to add?
Leigh Sims-Poston, BS, MT(ASCP)
Lina Ho, BScPhm, RPh, ACPR
Getting the most out of your ISBT
The use of Thiotepa in preparative regimens technology partners
for hematopoietic cell transplantation
Geoffrey Browne
Philippe Bouchard, BPharm, MSc, BCOP
CAG • Canadian
Apheresis Society
Canadian
Hematology Society
9
Thursday, June 12, 2014
4:00pm – 4:15pm
Health Break and Poster Group 1 Presentations
Health break located in Atlantic Ballroom, Poster group presentations located in Commonwealth Ballroom
Session 3A: CBMTG National Registry Steering Meeting
4:15pm – 6:15pm
Chair: Kristjan Paulson, MD
Session 3B: Networking session for Advanced Practice
Nurses and Nurse Practitioners
Maritime Room • 4:15pm – 5:15pm
Chairs: Jennifer Wiernikowski, MN, NP-Adult, CON(C), Jo-Ann
Edwards, NP
6:15pm – 7:30pm
Welcome Reception with Exhibits
Atlantic Ballroom and Foyer
Friday, June 13, 2014
7:00am – 7:00pm
Coat Check
7:00am – 4:00pm
Speaker Services
Northumberland Room
7:30pm – 8:45am
Symposium #2: Breakfast
9:00am – 12:00pm
Session 4: Joint Session CBMTG, CHS, Vector
Chairs: Stephen Couban, MD, FRCPC, Joanne Hickey, MD, FRCPC
9:00am: Human bone marrow failure: New treatment and new pathophysiologies
Neal Young, MD
10:00am – 10:20am Health Break in the Atlantic Ballroom
10:20am: Thrombosis and Malignancy: Management of complicated cases
Sudeep Shivakumar, MD, FRCPC, Marc Carrier, MD, MSc, FRCPC
11:10am: News from the PNH network
10:00am – 10:20am
12:00pm – 2:00pm
Danièle Marceau, MD
Health break located in Atlantic Ballroom, Poster group presentations located in Commonwealth Ballroom
Symposium #3: Lunch
Session 5: Age and Transplant
CHS Educational Session
Chairs: Gizelle Popradi, MD, FRCPC,
Jo-Ann Edwards, NP
For more information please see page 21
2:00pm – 3:30pm
3:30pm – 4:00pm
2:00pm:
Allogeneic transplant for
older AML patients: Too
little or too much?
2:45pm: You’re going to do what?!
A Case Study
Lunenburg Room • 2:15pm – 3:45pm
Harbour Suite AB and Boardroom
2:00pm – 6:00pm
Andrew Artz, MD, MS
Wanda Hasegawa, MD,
Jo-Ann Edwards, NP,
Christy Simpson, PhD
Health break located in Atlantic Ballroom, Poster group presentations located
in Commonwealth Ballroom
10
CAG Educational Sessions
CAG • Canadian
Apheresis Society
Canadian
Hematology Society
Session 6: Choosing the Best Donor
Harbour Suite AB and Boardroom
2:00pm - 6:00pm
Chairs: Andrea Kew, MD, Marie Tulloch, MLT
4:00pm – 6:00pm
How do we build the best registry?
4:00pm: 4:20pm:
4:40pm:
5:00pm:
Mindy Goldman, MD, FRCPC
Donor selection: Optimizing clinical outcomes and donor safety
John Miller, MD, PhD
KIR typing and its clinical relevance
Wing Leung, MD, PhD
Case Studies
Mindy Goldman, MD, FRCPC, John Miller, MD, PhD, Wing Leung, MD, PhD
6:00pm – 7:00pm
CBMTG Annual General Meeting
Harbour Suite AB
7:30pm – 9:00pm
Symposium #4: Dinner
Saturday, June 14, 2014
7:00am – 7:00pm
Coat Check
8:00am – 3:00pm
Speaker Services
Northumberland Room
7:30am – 8:45am
Symposium #5: Breakfast
Session 7A: Adult Clinical
Session 7B: Pediatric Clinical
Maritime Room
Chairs: Imran Ahmad, MD, John Kuruvilla, MD Chairs: Conrad Fernandez, MD, FRCPC,
David Mitchell, MD, FRCPC
9:00am – 12:00pm
9:00am: How can we improve
outcomes of patients with
relapsed/refractory DLBCL in
the Rituximab era
Craig Moskowitz, MD
9:00am: Metabolic disorders in the
age of expanding newborn
programs
Joanne Kurtzberg, MD
9:55am – 10:10am Health Break located
9:55am – 10:10am Health Break located
10:10am:High dose therapy for
relapsed Hodgkin lymphoma:
Is that all there is?
Michael Crump, MD, FRCPC
10:10am: KIR typing
Wing Leung, MD, PhD
in the Atlantic Ballroom
11:05am: Consolidation and
maintenance therapy after
autologous transplant for
multiple myeloma
Philip L. McCarthy, MD
9:55am – 10:10am
Harbour Suite AB • 8:30am – 5:00pm
in the Atlantic Ballroom
11:05am: Assessment of MRD pre- and
post-transplant in children
with ALL – Impact on
transplant decision making
Peter Bader, MD
in the Fundy Room
CAG • Canadian
Apheresis Society
Canadian
Hematology Society
11
12:00pm – 2:00pm
Symposium #6: Lunch
Harbour Suite AB • 8:30am – 5:00pm
Session 8: Hans Messner Lectureship
2:00pm – 3:00pm
Chairs: Stephen Couban, MD, FRCPC, Wanda Hasegawa, MD
Primary refractory leukemia – What to do next?
Richard Larson, MD
3:00pm – 3:15pm
in the Fundy Room
3:15pm – 4:15pm
Lunenburg Room
Session 9: Oral Abstract Presentations
Chairs: Silvy Lachance, MD, FRCPC, CSPQ, Christopher Bredeson, MD, MS, FRCPC
Session 10: Fred Saunders Debate
Chairs: Lynn Savoie, MD, Kylie Lepic, MD
4:15pm – 5:15pm
“Be it resolved that patients with acute lymphoblastic leukemia should have an
allogeneic transplant in CR1”
For the resolution: Daniel Weisdorf, MD
Against the resolution: Matthew Seftel, MD, MPH, MRCP, FRCPC
5:15pm – 5:45pm
7:00pm Onwards
Closing Remarks
Evening Social
Waterfront Warehouse
See details on page 63
Sunday, June 15, 2014
8:00am – 9:00am
Symposium #7: CAG Breakfast Symposium
Harbour Suite AB
9:00am – 12:00pm
CAG Sessions
Harbour Suite AB
12
CAG • Canadian
Apheresis Society
Canadian
Hematology Society
CBMTG Committee and Special Interest Group Meetings
Clinical Trials Network Meeting
Thursday, June 12, 1:00pm – 4:00pm
Advanced Practice Nurses and Nurse
Practitioners Networking Session
Harbour Suite AB
The mission of the CBMTG-CTN is to improve the safety, availability,
and efficacy of hematopoietic stem cell transplantation for adults and
children in Canada and to perform clinical research trials that will
define optimal hematopoietic stem cell transplantation for adults and
children. This committee strives to conduct laboratory research that
will translate into more effective treatments with reduced short and
long-term side effects and to build partnerships that will help fulfill the
missions of the Canadian Blood and Marrow Transplant Group and
improve the health of adults and children throughout the world.
Maritime Room
All advanced practice nurses and nurse practitioners are invited to
attend this networking session. We encourage you to take advantage
of this opportunity to connect with APN and NP nurses from across
Canada. Refreshments will be served.
This session will be immediately followed by the Interdisciplinary
Psychosocial Special Interest Group meeting.
All conference delegates are invited to attend this session.
Interdisciplinary Psychosocial Special
Interest Group Meeting
National Registry Steering Meeting
Thursday, June 12, 4:15pm-6:15pm
The purpose of the national registry Steering Committee is to provide
national oversight and direction to the Canada-wide registry.
All conference delegates are invited to attend this session.
Laboratory Technologists Special Interest
Group Meeting
Lunenburg Room
The laboratory technologist special interest group is a networking/
resource opportunity for laboratory professionals. It focuses on
technical and regulatory issues. The group currently has 40 members
from across Canada and continues to grow along with CBMTG.
All laboratory technologist conference delegates are invited to join
this special interest group and attend this face-to-face meeting at the
annual conference.
Maritime Room
The CBMTG Interdisciplinary Psychosocial Special Interest Group (SIG)
invites any interested CBMTG members to join this newly formalized
group focused on enhancing the psychosocial and supportive care
provided to patients undergoing HSCT. Over the past two years a draft
terms of reference and list of priorities has been drafted. This meeting
will officially launch the work of this group. Work to date will be
presented, partnerships explored and a preliminary list of objectives
for 2014-2015 will be discussed.
Webinar Planning Committee Meeting
Friday, June 13, 3:30pm – 3:45pm
Tradewinds
The purpose of the webinar planning committee is to guide the
association in developing educational webinars for BMT health
care workers.
All delegates who wish to be included in the planning process for the
CBMTG webinar series are invited to attend this meeting.
We encourage all delegates to attend a CBMTG committee or special interest group meeting! Please note that in order to become
a member of a committee or SIG you must be a current member of the CBMTG.
13
Session Summaries
Session 1: Joint Session Canadian Blood
and Marrow Transplant Group (CBMTG)
and Canadian National Transplant
Research Program (CNTRP)
Thursday, June 12, 2014 | 8:00am – 11:00am
FACING A COMMON ENEMY, VIRAL INFECTIONS IN SOT
AND AHCT
Silvy Lachance, MD, FRCPC, CSPQ, Hôpital Maisonneuve-Rosemont, Montreal, PQ, Canada
Marie-Josée Hébert, MD, FRCPC, Co-Director, Canadian National Transplant
Research Program (CNTRP), Montreal, PQ, Canada
Atul Humar, MD, FRCPC, University of Toronto, Toronto, ON, Canada
Upton Allen, MBBS, MSc, FAAP, FRCPC, The Hospital for Sick Children, Toronto, ON, Canada
Jean-Sébastien Delisle, MD, PhD, Hôpital Maisonneuve-Rosemont, Montreal, PQ, Canada
Steven Paraskevas, MD, PhD, McGill University, Montreal, PQ, Canada
Lori West, MD, PhD, Director, Canadian National Transplant Research Program
(CNTRP), Edmonton, AB, Canada
Kirk Schultz, MD, BC Children’s Hospital, Vancouver, BC, Canada
The Canadian National Transplant Research Program (CNTRP) unites the
solid organ transplant (SOT), critical care and donation, and allogeneic
hematopoietic cell transplant (AHCT) researcher communities and as
such, is the only national initiative of its kind in the world. One of the
main ambitions of the CNTRP is to provide a comprehensive platform
where SOT and AHCT scientists can collaborate and provide fresh ideas
on various central issues such as organ and cell donation, immune
tolerance and opportunistic infections.
Viral infections plague both SOT and AHCT recipients. This joint CNTRPCBMTG session will focus on ongoing work within the CNTRP as well
as on emerging aspects of virus-host interactions and cell therapy aimed
at treating opportunistic viral diseases. Dr Atul Humar, lead of CNTRP
Viral Pathogenesis Project and head of transplantation at the University
Health Network in Toronto will provide the keynote presentation on
several basic and translational aspects of virus-related complications after
transplantation. Following this presentation, Dr Upton Allen from the
Hospital for Sick Children in Toronto and co-lead of the CNTRP Pediatric
Project will discuss host-pathogen interactions predisposing certain
patients to viral infections. Finally, Dr Jean-Sébastien Delisle, CNTRP
scientist who is leading a T-cell adoptive immunotherapy program at
Hôpital Maisonneuve-Rosemont in Montreal, will discuss cellular therapy
approaches to prevent and treat viral infections post-transplantation.
This session will also emphasize the importance of collaborations and
include a discussion about the interactions between the SOT and AHCT
communities within the CNTRP.
14
Session 2A: Clinical Trials Network Meeting
Thursday, June 12, 2014 | 1:00pm – 4:00pm
Donna Wall, MD, Cancer Care Manitoba, Winnipeg, MB, Canada
Session 2B: Multidisciplinary Allied Health
ACCESS TO HIGH COST TREATMENTS: NAVIGATING THE
COMPLEX WORLD OF ONCOLOGY DRUG COVERAGE
Mary Lou Robertson, BA, BSW, RSW, Capital Health Cancer Care Program, Halifax,
NS, Canada
This session will provide an opportunity for professionals from a range of
health care backgrounds to learn how drugs are approved, funded, and
accessed in Canada. Participants will gain an understanding of how drugs
move from trials to market and how insurers and provinces make decisions
on whether to fund them. Participants will gain a stronger appreciation
of provincial funding disparities and the growing presence of private
insurance in funding high cost treatments in oncology. Specific attention
will be given to how to understand and navigate insurance and public
plans, how to deal with funding rejections or complex cases, and how to
navigate the growing role of patient assistance programs. By the end of
the session, participants will have a better understanding of potential drug
funding challenges and how to deal with them. Case examples will be
used and there will be time provided for questions and answers. This is an
ideal session for clinic nurses, nurse practitioners, pharmacists, pharmacy
technicians, physicians, social workers, and program managers.
NEAR DEATH EXPERIENCES: HOPE, HYPOXIA AND HYPOTHESIS
David Maginley, M. Div., Nova Scotia Cancer Centre, Halifax, NS, Canada
In 2011–2012, about half (45%) of Canadian cancer deaths occurred
in acute care hospitals. Health care providers are repeatedly exposed to
death and terminal prognosis, providing compassion care to stave off
what, in the end, is a 100% statistic. We all die. But a growing body
of research indicates that we do not end – something much greater
occurs. Health care staffs are among those most likely to witness this
most mysterious and even beautiful aspect of death – visitations by
deceased loved ones, visions of angels, stories of a patient glimpsing
the other side. These transcendent moments do not fit into the medical
model, one that wrestles with the nature of consciousness itself, and
so have been predominantly dismissed as hallucination or reduced to
bioelectrical cascade.
Near Death Experiences (NDEs) are mystical phenomena in which a
patient may have an out-of-body experience, feel profound peace and
love, encounter deceased relatives or spiritual beings, obtain unique
knowledge, be told to return, and have permanent physiological and
life changes. Many accounts include corroboration of events witnessed
while dead. Accounts worldwide show that while details are culturally
specific, NDEs occur across all belief systems, nationalities, ages
educations and time periods.
This presentation will explore the characteristics of NDEs through
ten years of work with the dying. We will examine various medical
explanations, review the unique and permanent affects NDEs have
on people’s lives, memory, intelligence and physiology, and consider
the implications of an integrative theory of consciousness which has
developed thanks to advances in medical imaging and new models of
the mind/body connection.
APREPITANT IN BLOOD AND MARROW TRANSPLANTATION: TO
ADD OR NOT TO ADD?
Lina Ho, BScPhm, RPh, ACPR, Princess Margaret Hospital, Toronto, ON, Canada
Aprepitant (Emend®) is an antiemetic drug with a different mechanism of
action from pre-existing antiemetics. As such, the addition of Aprepitant
to 5-HT3 antagonist plus dexamethasone is now standard of care for
patients receiving highly emetogenic chemotherapy, mostly in the
solid tumour setting (combined anthracycline and cyclophosphamide
regimens and high-dose cisplatin regimens). Although most of the
conditioning regimens in BMT are also highly emetogenic, the use of
Aprepitant in this setting is less characterized. Due to various factors
such as local funding models and concern for drug interactions, different
practices are seen in transplant centers across Canada. The objective of
this presentation is to:
1. Explain the mechanism of action of Aprepitant and potential drug
interactions commonly seen in the BMT setting
2. Review three recent publications on the use of Aprepitant in
autologous and allogeneic BMT
3. Discuss with the audience the considerations for adding Aprepitant
to the antiemetic regimens in various BMT conditioning protocols
THE USE OF THIOTEPA IN PREPARATVE REGIMENS FOR
HEMATOPOIETIC CELL TRANSPLANTATION
Philippe Bouchard, BPharm, MSc, BCOP, Hôpital Maisonneuve-Rosemont, Montreal,
QC, Canada
Although not commercially available in Canada, the alkylating agent
thiotepa is increasingly used in preparative regimens for hematopoietic
cell transplantation. The pharmacology of the agent and the evidence
supporting its use prior to transplantation are reviewed.
Hematological toxicity limits the use of thiotepa in solid tumor
oncology. At doses used in hemtopoietic cell transplantation, significant
myelosuppression is expected.
Non-hematological toxicities are also discussed: skin cleansing is
recommended in order to prevent dermatological toxicity. Mucosal
toxicity is also of concern and requires standard preventative and
therapeutic management.
Finally, recommendations for drug authorization and acquisition,
preparation and administration of thiotepa are provided.
Session 2C: Laboratory Technologists Session
ISBT 128: FROM THE GLOBAL PICTURE TO THE DETAILS
Pat Distler, MS, MT(ASCP)SBB, ICCBBA, San Bernadino, CA, USA
Increasing numbers of cellular therapy facilities around the world are
implementing ISBT 128, an international terminology, coding, and
labeling system. The World Health Organization has an organizationwide initiative for the governance of medical products of human origin
(MPHO) that includes the global use of ISBT 128. ISBT 128 is endorsed
by many cellular therapy professional societies.
This session will provide information about the global status of ISBT
128, major steps in implementation, and label design. It will cover the
changes made to the terminology in August 2013 and the impact of
these changes to current users of the system.
It will:
1. Discuss the global strategy of ISBT 128 implementation for medical
products of human origin and how cellular therapy facilities fit into
this vision
2. Describe key features of the ISBT 128 label design identifying
which elements are rigidly standardized and which are not
3. List key steps in implementation of ISBT 128
4. Identify recent changes to the terminology and the impact of these
changes to current users
ISBT 128 PRODUCT CODE SELECTION: WHICH CODES DO I
WANT? WHICH CODES DO I NEED?
Leigh Sims Poston, BS, MT (ASCP), Chester, VA, USA
This session will focus on the details of product code selection for
cellular therapy products. Many users try to apply individual preferences
to product code selection. This session will help the user understand
how to apply product classes and attributes to identify a product code
within the existing database or to request a new product code if needed.
The session will review the tools and resources available within ICCBBA
to assist the user in the code selection process.
This session will:
1. Review the ISBT 128 terminology concept for cellular therapy and
15
2013 terminology changes to help the user better understand the
tools used to create product code descriptions
2. Review product code selection through scenarios and audience
participation
Session 4: CBMTG Joint Session with
Canadian Hematology Society and Venous
Thrombosis Clinical Trials Organization
GETTING THE MOST OUT OF YOUR ISBT TECHNOLOGY PARTNERS
Friday, June 13, 2014 | 9:00am – 12:00pm
Geoffrey Browne, Stemsoft Software Inc., Vancouver, BC, Canada
An ISBT implementation can feel like a daunting task, but you are not
alone. Whether you intend to buy, build or borrow your ISBT solution,
this session will talk about getting the most out of the vendors and inhouse technology specialists.
This session will:
•
Review the key phases of an ISBT technology implementation from
selection through validation
•
Discuss the potential cost and regulatory implications of hardware,
software and label design choices
•
Discuss the relative merits of buying, building or borrowing your
ISBT solution from another department
•
Demonstrate how an ISBT solution can be integrated into your
existing workflow
Poster Group 1 Presentations
Session 3A: CBMTG National Registry
Steering Meeting
Kristjan Paulson, MD, University of Manitoba, Winnipeg, MB, Canada
Neal Young, MD, NIH, National Heart, Lung, and Blood Institute, Bethesda, MD, USA
Dr. Young will discuss recent advances in the treatment of aplastic
anemia, especially the utility of the thrombopoietin synthetic
mimetic eltrombopag, a drug which appears to stimulate the human
hematopoietic stem cell. The new telomeropathies, which manifest as
marrow failure, are due to mutations in the telomere repair complex;
telomeres also shorten secondary to stem cell proliferation in the
setting of marrow stress. Telomere biology appears to predict clonal
evolution, the development of myelodysplasia and acute leukemia in
setting of immune-mediated aplastic anemia. Telomere repair may be
achievable using an old remedy, androgens, which in vitro upregulate
telomerase gene activity and in vivo improve blood counts in patients
with telomerase deficiency and elongate leukocyte telomeres.
THROMBOSIS AND MALIGNANCY: MANAGEMENT OF
Complicated CASES
Sudeep Shivakumar, MD, FRCPC, Dalhousie University/QEII Health Sciences Centre,
Halifax, NS, Canada
Marc Carrier, MD, MSc, FRCPC, University of Ottawa, Ottawa, ON, Canada
Patients with malignancies are at an increased risk of venous
thromboembolism. Hematologic malignancies post unique challenges
in the treatment of thrombosis, including the management of central
venous catheters, thrombocytopenia, and recurrent events. These issues
will be presented in case-based format.
Session 3B: Advanced Practice Nurse/Nurse
Practitioner Networking Session
News from the PNH network
Jennifer Wiernikowski, MN, NP Adult, CON(C), Hamilton Health Sciences Centre,
Hamilton, ON, Canada,
Jo-Ann Edwards, NP, QEII Health Sciences Centre, Halifax, NS, Canada
16
HUMAN BONE MARROW FAILURE: NEW TREATMENT AND
NEW PATHOPHYSIOLOGIES
Danièle Marceau, MD, CHU de Quebec, Quebec, PQ, Canada
Friday, June 13, 2014 | 10:00am – 10:20am
Session 5: Age and Transplant
Session 6: Choosing the Best Donor
Friday, June 13, 2014 | 2:00pm – 3:30pm
Friday, June 13, 2014 | 4:00pm – 6:00pm
ALLOGENEIC TRANSPLANTION FOR AML: TOO MUCH OR
TOO LITTLE?
HOW DO WE BUILD THE BEST REGISTRY?
Andrew Artz, MD, MS, University of Chicago Medicine, Chicago, IL, USA
This presentation will focus on donor registry issues related to
the recruitment and retention of the “best donor” for potential
transplantation. Challenges in donor recruitment will be discussed from
the perspective of the OneMatch donor registry and include recruiting
and retaining registrants that are most likely to be selected as donors,
and establishing criteria in contentious areas, such as a history of high
risk behaviors, pain syndromes, or mental health disorders. Case studies
will be presented to illustrate some of these issues.
Acute myeloid leukemia (AML) is both more common and more
fatal in older adults relative to younger patients. Observational data
have shown promising long-term outcomes in older AML patients
undergoing allogeneic hematopoietic cell transplantation (HCT) relative
to historical controls although prospective data are sorely lacking. Both
the proportion and absolute number of patients 60 years (and 70 years
of age) undergoing allogeneic HCT for AML have risen steadily from
2000 to 2010. Still, the enthusiasm to extend HCT to older patients is
limited by concerns over transplant related morbidity and mortality and
the absolute long-term benefit. Better methods to gauge patient health
and, by extension, tolerance to transplant are gaining acceptance.
Comorbidity by the Hematopoietic Cell Transplantation – Comorbidity
Index (HCT-CI) facilitates risk stratification but high comorbidity alone
does not preclude long-term survival after allogeneic HCT. More
detailed health inventories through geriatric assessment and serum
biomarkers better captures patient health by documenting the presence
or absence of deficits across numerous health domains. For example,
the combination of comorbidity and self-report functional status
may enhance prognostication sufficient to reliably inform transplant
candidacy.
Clarity is emerging regarding donor sources for older AML patients. Older
matched sibling donors produce equivalent, if not better, outcomes
compared to matched unrelated donors. In addition, alternative donor
sources are emerging as acceptable grafts for patients lacking matched
donor options. Still, for patients (and donors) 70 years and older,
published experience is very limited and requires careful pre-transplant
evaluation. The field sorely needs prospective comparative trials to fully
ascertain the benefits and risks of allogeneic HCT in older AML patients.
You’re going to do what?! A case study
Jo-Ann Edwards, NP, QEII Health Sciences Centre, Halifax, NS, Canada,
Wanda Hasegawa, MD, Provincial Stem Cell Transplant Program, Dalhousie
University, Halifax, NS, Canada
Christy Simpson, PhD, Dalhousie University, Halifax, NS, Canada
Using a case study, this interactive session will explore ethical issues in
the context of decisions around stem cell transplants.
Friday, June 13, 2014 | 3:30pm – 4:00pm
Mindy Goldman, MD, FRCPC, Canadian Blood Services, Ottawa, ON, Canada
DONOR SELECTION: OPTIMIZING CLINICAL OUTCOMES AND
DONOR SAFETY
Minneapolis, MN, USA
Hematopoietic cell transplantation (HCT) is used to treat an everincreasing number of patients with malignant and nonmalignant
diseases and would not be possible without the altruistic donors of
marrow, PBSC and cord blood. This session will discuss how to select
which potential HCT donor is likely to be associated with the best clinical
outcomes for a particular patient. In addition to HLA matching, this
session will address how donor demographics including age, gender,
ABO mismatch and parity for female donor may impact survival and
GVHD. From a donor safety perspective, a careful medical assessment
of donors to identify increased risks of donation is an integral part of
the donation process. The evaluation of HCT donors differs from that
of blood, tissue and organ donors and this presentation will provide
an overview of the medical evaluation process to determine donor
suitability and ensure HCT product safety.
KIR TYPING AND ITS CLINICAL RELEVANCE
Wing Leung, MD, PhD, St. Jude’s Children Hospital, Memphis, TN, USA
HLA and KIR genes are the two most polymorphic families in human
genome. Donor- and patient-derived products from these two gene
families determine the T-cell and NK-cell alloreactivity in hematopoietic
cell transplantations, thus substantially affecting the risk of graft
rejection, graft-versus-host disease, infection, and leukemia relapse.
This lecture will provide an overview of KIR immunogenetics, NK cell
biology, clinical KIR typing, KIR mismatch models, KIR effects on patient
outcomes, and algorithm in donor selection. The goal is to optimize NKcell and T-cell alloreactivity to improve transplant results. Controversies
and future research opportunities will be discussed.
17
CASE STUDIES: CHOOSING THE BEST DONOR
Mindy Goldman, MD, FRCPC, Canadian Blood Services, Ottawa, ON, Canada,
Minneapolis, MN, USA,
will help to define optimal approaches to long term disease control of
multiple myeloma.
Session 7B: Pediatric Clinical
Saturday, June 14, 2014 | 9:00am – 12:00pm
Session 7A: Adult Clinical
Saturday, June 14, 2014 | 9:00am – 12:00pm
HOW CAN WE IMPROVE THE OUTCOMES OF PATIENTS WITH
RELAPSED/REFRACTORY DLBCL IN THE RITUXIMAB ERA
Craig Moskowitz, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
For relapsed/refractory patients who are candidates for HDT/ASCT,
available second-line regimens include DHAP, ICE, ESHAP GDP, or
GEMOX, among others. There is presently no data to support superiority
of one regimen over another, so choice of regimen should be selected
based on the patient’s prior therapy, comorbidities, and risk profile of
the regimen. The role of Rituximab does not appear to have improved
the efficacy of second-line therapy, although it is included. That being
said, the prognosis for cure with HDT/ASCT has significantly worsened in
the rituximab era, with more patients being cured in the upfront setting
and higher risk patients relapsing after R-CHOP. Only half of patients
who received prior rituximab achieved a response to second-line
therapy, compared to an 83% response rate in rituximab naïve patients.
The role or prognostic factors, clinical and molecular as well as preASCT PET imaging are important, however how to use these effectively
remains controversial as well. These issues will be discussed at the
seminar. However it is clear to lymphoma experts that management
of relapsed/refractory DLBCL is at a standstill and novel therapies are
critically needed.
HIGH DOSE THERAPY FOR RELAPSED HODGKIN LYMPHOMA: IS
THAT ALL THERE IS?
Michael Crump, MD, FRCPC, Princess Margaret Hospital, Toronto, ON, Canada
CONSOLIDATION AND MAINTENANCE THERAPY AFTER
AUTOLOGOUS TRANSPLANT FOR MULTIPLE MYELOMA
Philip L. McCarthy, MD, Roswell Park Cancer Center, Buffalo, NY, USA
Consolidation and maintenance therapy after autologous hematopoietic
stem cell transplant improves and maintains response and disease
control in MM patients. Consolidation is usually a more intense therapy
design to improve response whereas maintenance may improve
response but is more often designed to control disease long-term
and maintain response. The proteasome inhibitor Bortezomib and the
immunomodulatory drugs thalidomide and lenalidomide have been
used alone or in combination as both consolidation and maintenance.
The lecture will discuss the current trials and those in progress that
18
METABOLIC DISORDERS IN THE AGE OF EXPANDING
NEWBORN PROGRAMS
Joanne Kurtzberg, MD, Robertson Clinical and Translational Cell Therapy Program,
Durham, NC, USA
KIR TYPING
Killer-cell immunoglobulin-like receptors (KIRs) are highly polymorphic.
Among known NK receptors, KIRs are the primary determinant of NK
cell response. KIRs are also expressed in subsets of T cells. Clinically,
KIR typing is not only useful for allogeneic donor selection but also
for prognostication in autologous settings. This lecture will provide an
overview of the three levels of clinical KIR typing: (1) genotyping for
gene content and A/B haplotype categorization, (2) phenotyping for
gene expression and number of KIR+ cells, and (3) allelotyping for
functional strength. Cases will be discussed with audience participation
to demonstrate the approach to interpretation of KIR typing results.
ASSESSMENT OF MRD PRE- AND POST-TRANSPLANT IN
CHILDREN WITH ALL – IMPACT ON TRANSPLANT DECISION
MAKING
Peter Bader, MD, Hospital for Children and Adolescents, Frankfurt, Germany
During the past decades, tremendous progress has been made in
the treatment of children and adolescents with acute lymphoblastic
leukemia (ALL). Nowadays more than 80% of children with ALL can
be cured with intensive, risk-based chemotherapy protocols. Several
cytogenetic and response-based risk factors which are associated with
poor outcome could be identified either at presentation, during therapy
or after relapse. Allogeneic stem cell transplantation (SCT) has been
of benefit for many children with these risk factors who relapsed after
initial chemotherapy (e.g. relapse on treatment, early relapses and
others). Relapse remains the major cause for treatment failure after
allogeneic SCT for high risk pediatric ALL.
In 1998 the retrospective study of Knechtli et al. showed that the level
of minimal residual disease (MRD) immediately prior to transplantation
represented an important prognostic factor for successful allogeneic
SCT. These findings were confirmed by other retrospective studies all
showing that patients who entered transplantation with high MRD load
faced an extremely elevated risk to develop relapse after transplantation.
Based on the potential clinical impact of these studies the European
Study Group on MRD detection in ALL (ESG-MRD-ALL) was founded.
This group standardized MRD methods and set up a quality assurance
network as the technical fundament for multi-centre trials. Recently, we
could confirm in a prospective study in children with relapsed ALL that
the risk of subsequent post-transplant relapse was strongly depending
on the MRD level at the time of transplant. The cumulative incidence of
relapse (CIR) was 0.57 for patients with an MRD load of ≥10-4 leukemic
cells compared to 0.13 for patients who received transplant while having
an MRD load of <10-4 leukemic cells. These results strengthened the
need for further studies aiming to improve the quality of remission
prior to transplant. However, MRD assessment before transplantation
could scarcely identify those individuals with post-transplant impending
relapse who need and might profit from intervention therapy. For
those, additional interventions can influence outcome by augmenting
or improving an immune graft versus leukemia (GvL) effect after
transplantation. Such approaches include abrupt cessation or rapid
tapering of immune suppression, administration of cytokines, and donor
lymphocyte infusion (DLI) with or without cytokines. To elucidate the
importance of MRD characterization post-transplant we have evaluated
the results out of the prospective ALL-BFM-SCT-2003 trial, which will be
presented and discussed.
Saturday, June 14, 2014 | 9:55am – 10:10am
Session 8: Hans Messner Lectureship
Saturday, June 14, 2014 | 2:00pm – 3:00pm
PRIMARY REFRACTORY LEUKEMIA – WHAT TO DO NEXT?
Richard A. Larson, MD, University of Chicago, Chicago, IL, USA
Approximately 75% of young and middle aged adults with acute
myeloid leukemia (AML) will achieve a complete remission after one
or two courses of intensive remission induction chemotherapy. Primary
refractory leukemia is the cause for failure in most of the remainder.
Specific clonal cytogenetic abnormalities present at diagnosis identify
those at highest risk. Since allogeneic hematopoietic cell transplantation
can rescue some of these patients, a search for histocompatible donors
should begin at diagnosis. Pre-transplant conditioning therapy and
post-transplant therapeutic interventions are investigational and are
being studied in prospective trials.
Session 9: Oral Abstract Presentations
For information regarding the oral abstract presentations please see
page 23.
Session 10: Fred Saunders Debate
“BE IT RESOLVED THAT PATIENTS WITH ACUTE
LYMPHOBLASTIC LEUKEMIA SHOULD HAVE AN ALLOGENEIC
TRANSPLANT IN CR1”
For the Resolution: Daniel Weisdorf, MD, University of Minnesota, Minneapolis,
MN, USA
Dr. Daniel Weisdorf is Professor of Medicine, Division Chief of Hematology,
Oncology and Transplantation, Director of the University of Minnesota
Blood and Marrow Transplant Program and Associate Chair for clinical
research in the Department of Medicine. He is currently Senior Research
Advisor for the Center for International Bone Marrow Transplant Research
(CIBMTR) and Scientific Director for its Acute Leukemia Committee. He
is a past chair of the NIH-sponsored Blood and Marrow Transplantation
Clinical Trials Network (BMT CTN) Steering Committee and past-President
of the American Society of Blood and Marrow Transplantation. His clinical
and research interests are in application of blood and marrow transplant
therapies for hematologic malignancies as well as extensive study of the
clinical complications of transplantation including acute leukemia and
graft versus host disease (GVHD).
Against the resolution: Matthew Seftel, MD, MPH, MRCP, FRCPC, Princess
Margaret Hospital, Toronto, ON, Canada
Dr. Seftel is a hematologist/oncologist based at Princess Margaret
Hospital in Toronto. He leads the allogeneic blood and marrow
transplantation program and is a member of the leukemia group. He
is an associate professor at the University of Toronto in the division of
internal medicine. He is actively involved in clinical trials and outcomes
based research related to the hematologic malignancies and BMT.
19
Canadian National Transplant Research Program
Annual Scientific Meeting 2014
June 10 - 12, 2014 • The Westin Nova Scotian, Halifax, Nova Scotia
Conference Co-Chairs: Dr. Marie-Josée Hébert, CRCHUM, Dr. Jean-Sébastien Delisle, CR Hôpital Maisonneuve-Rosemont
The purpose of the CNTRP annual meeting is to encourage researchers
from the solid organ transplant (SOT), allogeneic hematopoietic cell
transplant (AHCT), and critical care and donation communities to think
differently by promoting synergistic collaboration and ample networking
opportunities and to strengthen the cross-project/core integrations
within the CNTRP and encourage new collaborations
This CNTRP session will focus on ongoing work within the CNTRP, with
highlights presented from each of the 3 supportive cores as well as the
six collaborative projects. Following these updates, external advisory
board member Dr. Kathryn Wood will share her views on the progress of
the program, followed by a discussion on future directions by the CNTRP
Director, Dr. Lori West.
Become a member of the Canadian Blood
and Marrow Transplant Group!
Are you a Physician, Researcher, Nurse,
Pharmacist, Laboratory Technician, or
Program Coordinator working in blood and
marrow transplant? Join CBMTG and take
advantage of the exciting benefits that
membership has to offer!
Benefits:
•
•
•
•
•
•
•
Discounted rate for the annual conference
Free registration for association educational webinars
Get involved with committees and working groups
Opportunity to apply for small budget research grants
Access to Sosido
Network with your colleagues in BMT
Help advance the BMT profession across Canada!
Visit cbmtg.org today to learn more!
20
AGENDA
The Canadian Apheresis Group (CAG) Canadian Association of Apheresis Nurses (CAAN)
The Canadian Hematology Society (CHS)
34TH ANNUAL GENERAL MEETING AND SCIENTIFIC SESSIONS
June 13 -15, 2014 • The Westin Nova Scotia Halifax, Nova Scotia
7:30am – 8:45am
Registration
Harbour Suite AB
7:30am – 8:45am
CBMTG Breakfast Symposium
Joint session CHS, CBMTG, VECTOR
Moderators: Stephen Couban, MD and Joanne Hickey, MD, FRCPC
9:00am: 9:00am – 12:00pm
12:00pm – 2:00pm
2:00pm – 6:00pm
Human bone marrow failure: New treatment and new pathophysiologies • Dr. Neal Young
10:00 – 10:20am: Break (Atlantic Ballroom)
10:20am
Thombosis and Malignancy: Management of complicated cases • Sudeep Shivakumar, MD, FRCPC
11:10am:
Overview of Paroxismal Nocturnal Hemoglobinuria (PNH) • Danièle Marceau, MD
and Marc Carrier, MD, MSc, FRCPC
CBMTG Lunch Symposium
Planning Group Meeting
Boardroom
2:00 – 6:00pm
CAAN Nursing Workshop
Hemophilia therapies
Welcome Remarks
2:15pm – 3:00pm
In the clinic and in the future
Harbour Suite AB • 2:00 – 5:00pm
Eduard Cojocari, RN, Chantal Goupil, RN
Differentiation of Thrombotic
Microangiopathy
Dr. Pavenski – SMH
ABO Incompatible Kidney transplants
Lunenburg Room
Dr. P. Moorhead
3:00pm – 3:45pm
Single unit transfusion
Dr. E. Kahwash
Megan Buchholz –SMH
SDP “who is doing what?”
Kerri Gallo – LHSC
Collection Efficiency in Stem Cell
Collections
Eduard Cojocari
An Overview of THERAKOS®
Photopheresis
James V. Greco
6:30pm Onwards
CAAN Nursing Evening Social
Salty’s
7:30am – 8:30am
8:30am – 8:45am
Registration and Breakfast
Harbour Suite AB
Welcome
Harbour Suite AB
Review of Agenda
21
CAG 2014 PE Data Review
Harbour Suite AB
Plasma exchange procedures • Dr. Rock
Neurological/ metabolic and gastroenterological • Dr. Pavenski
Hematological • Dr. Foley
Renal/collagen vascular and dermatological • Dr. Clark
Miscellaneous • Dr. Amber
8:45am – 11:45am
Photopheresis • Dr. Klassen
Discussions and Recommendations • All
10:00am – 10:30am BREAK
Type and amount of fluids used • Dr. Laroche
Adverse reactions/deaths • Dr. Quarni
Hepatitis E Post Plasma Exchange • Dr. Rock
Pathogens in blood • Dr. Pavenski
11:45am – 12:00pm
TMA Registry • Dr. Rock
Harbour Suite AB
12:00pm – 1:30pm
LUNCH
Tradewinds
CBS Report • Dr. M. Golden
1:30pm – 3:30pm
SDP Use in Patients • Dr. Pavenski
Harbour Suite AB
Rituximab Study • Dr. Foley
Discussion/Direction • All
3:30pm – 3:45pm
BREAK
Harbour Suite AB
Physician Workshop
Maritime Room
3:45pm – 5:00pm
aHUS/TMA • Dr. Lawrence
The Pexivas Study • Dr. Clark
7:00pm Onwards
CAAN Nursing Workshop
Harbour Suite AB
CAAN round table discussion / Business Meeting
CBMTG Social Event Pre-registration is required to attend this event.
Sunday, June 15, 2014
22
8:00am – 9:00am
Breakfast
Harbour Suite AB
9:00am – 9:30am
Photopheresis: Mechanisms of action • Dr. Marcu
Harbour Suite AB
9:30am – 10:00am
cGVHD NIH Classified • H. Kerr
Harbour Suite AB
10:00am – 10:30am
Plerixafor • TBA
Harbour Suite AB
10:30am – 11:00am
BREAK
Harbour Suite AB
11:00am – 11:30am
The Optia: Preformance in bone marrow processing • M. Pidduck
Harbour Suite AB
11:30am – 12:00pm
The Canadian stem cell data • Dr. Foley
Harbour Suite AB
Oral Abstract Index
#
Title
Topic
Presenting Author
01
A Randomized Trial of Rituximab vs. Observation Following
Autologous Stem Cell Transplantation (ASCT) for Relapsed or
Refractory CD20-Positive B Cell Lymphoma: Final Results of NCIC
CTG LY.12.
Clinical Trials and
Observations
Michael Crump,
CD34 Cell Dose is Correlated with Hematologic Recovery but
not Chronic Graft vs Host Disease: Results of the CBMTG Trial
Comparing G-CSF-Mobilized Peripheral Blood (G-PB) versus
G-CSF Stimulated Bone Marrow (G-BM) in Sibling Allografts for
Hematologic Malignancies
Clinical Trials and
Observations
Stephen Couban, MD
Plasma Levels of Mitochondrial DNA (MtDNA) Are Able to
Stimulate B Cells to Produce Proinflammatory Cytokines and
Are Increased at the Onset of Chronic Graft Versus Host Disease
Basic/Translational
Research
Kirk Schultz, MD
Cognitive Functioning as a Predictor of Medication
Management Ability Among Stem Cell Transplant Recipients
Pharmacy,
Nursing and Other
Transplant Support
Samantha Mayo
Utilization of Hematopoietic Stem Cell Products Cryopreserved
at the Time of Allogeneic Stem Cell Transplant
Laboratory/Quality
Muneer Abidi, MD
02
03
04
05
01. A Randomized Trial Of Rituximab Vs
Observation Following Autologous Stem
Cell Transplantation (ASCT) For Relapsed
Or Refractory CD20-Positive B Cell
Lymphoma: Final Results Of NCIC CTG LY.12.
Michael Crump MD FRCPC1, John Kuruvilla, MD1, C. Tom Kouroukis, MD,
MSc, FRCP(C)2, Ann Benger, MD, FRCP(C)2, Matthew C. Cheung, MD, FRCPC3,
Neil L Berinstein, MD3, Stephen Couban, MD, FRCPC4, Matthew D. Seftel,
MBChB, FRCP(C), MRCP8, Kang Howson-Jan, MD6, Armand Keating, MD1,
Massimo Federico, MD10, David A Macdonald, MD, FRCPC4, Harold J.
Olney, MD8, Morel Rubinger, MD5*, Michael Voralia9, A. Robert Turner,
MD, FRCPC10, Tara Baetz, MD11, Annette E Hay, MBChB12, Marina Djurfeldt,
MSc12, Ralph M. Meyer, MD2, Bingshu Chen, PhD12 and Lois Shepherd,
MD12
1
Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON,
Canada
2
Division of Malignant Hematology, Dept of Oncology, Juravinski Cancer Centre, Hamilton,
ON, Canada
MD, FRCPC
Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Health Sciences Centre, Halifax, NS, Canada
5
Cancer Care Manitoba, Winnipeg, MB, Canada
6
London Health Sciences Centre, London, ON, Canada
7
Department of Diagnostic and Clinical Medicine, and Public Health, University of Modena
and Reggio Emilia, Modena, Italy
8
Universite de Montreal, Montreal, QC, Canada
9
Saskatoon Cancer Centre, Saskatoon, SK, Canada
10
Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada
11
Department of Oncology, Cancer Centre of Southeastern Ontario, Queen’s University,
Kingston, ON, Canada
12
Queens University, NCIC Clinical Trials Group, Kingston, ON, Canada
3
4
Rationale
NCIC CTG LY.12 was an international randomized trial evaluating
two treatment strategies for patients (pts) with aggressive lymphoma
relapsing after or with progressive disease following primary therapy. The
first randomization demonstrated that gemcitabine, dexamethasone,
cisplatin (GDP) was non-inferior to and significantly less toxic than
dexamethasone, cytarabine, cisplatin (DHAP) as salvage therapy (ASH
2012). Here we report the results of the second randomization, testing
the ability of the CD20 antibody rituximab (R) administered post-ASCT
23
to improve event-free survival (EFS) compared to no further therapy.
Methods
Pts with CD20-positive aggressive lymphoma who underwent ASCT
after GDP or DHAP who had recovered from ASCT-related toxicities
and who remained clinically progression-free within 3-5 weeks posttransplant were stratified by centre, salvage regimen received, response
to salvage therapy (CR vs PR/SD) and prior treatment with R, and were
randomized using a minimization algorithm to receive R 375 mg/m2
every 2 months for 6 doses, or observation. Response assessment by CT
scanning was required at 3,7,13 and 25 mos post-ASCT or as needed
to evaluate possible disease recurrence. The primary endpoint of the
second randomization was 2 year EFS; to detect an improvement by
15% (from 50 to 65%, hazard ratio 0.62) required 142 events, with
a 2-sided α 0.05 and power 0.80. Because of the low event rate over
the last year and a projected time of many years to reach the protocol
specified event rate, the Data Safety Monitoring Committee approved a
request for study closure and analysis, with 118 events recorded.
Results
230 patients were randomized to R maintenance (115) or observation
(115). Baseline patients and disease characteristics were well balanced:
median age was 53 yrs, 28% were age >65 and 40% were female;
52% received GDP and 48% DHAP; 55% had an IPI score of 2 or more
at relapse/progression, and 17% had transformed (TR) from previous
indolent lymphoma. Response to salvage pre-ASCT: CR 24%, PR 58%;
70% had received R with chemotherapy prior to study enrolment,
and 69% received R with protocol salvage treatment. All analyses are
ITT. There have been 118 EFS events (R 53, observation 65). After a
median follow-up of 63 months, 2 year EFS was 64% for pts treated
with maintenance R vs 51% for those on observation (HR 0.74, 95% CI
0.48-1.14, p= 0.11); there was no difference in overall survival (OS) at
4 years (R 69%, observation 68%, p=0.64). Grade 3-4 neutropenia was
reported in 36% of pts on R maintenance vs 25% during observation;
and Gr 3-4 thrombocytopenia in 11% and 16%, respectively. Febrile
neutropenia occurred in 10 pts (9%) on R maintenance and 2 pts
(2%) on observation. Two year EFS was similar in subsets defined by
stratification variables at randomization: GDP salvage therapy: R 57.0%
vs observation 45.9% (HR 0.84, 95% CI 0.52-1.36), DHAP: R 70.0% vs
observation 57.1% (HR 0.68, 0.39-1.18); response to salvage CR/CRu:
R 69.0% vs 52.9% (HR 0.71, 0.32-1.6), PR: R 64.5% vs observation
57.4% (HR 0.90, 0.55-1.46); R use with prior treatment: R 53.7%
vs observation 42.0% (HR 0.81, 0.54-1.22); no prior R: R 83.3% vs
observation 70.6% (HR 0.64, 0.29-1.38). In multivariable analysis, only
age >60 was significantly associated with EFS; ECOG PS, treatment arm,
stage and extra-nodal disease were not significant.
02. CD34 Cell Dose is Correlated with
Hematologic Recovery but not Chronic
Graft vs Host Disease: Results of the CBMTG
Trial Comparing G-CSF-Mobilized Peripheral
Blood(G-PB) versus G-CSF Stimulated Bone
Marrow(G-BM) in Sibling Allografts for
Hematologic Malignancies.
Stephen Couban, MD1, Mahmoud Aljurf2, Silvy Lachance, MD3, Irwin
Walker, MBBS4, Cynthia L. Toze, MD, FRCP(C)5, Morel Rubinger, MD6,
Jeff H. Lipton, PhD, MD7, Stephanie J. Lee, MD, MPH8, Jeffrey Szer, MD9,
Richard Doocey10, Ian D Lewis, MB, BS, PhD11, Lothar B. Huebsch, MD12,
Kang Howson-Jan, MD13, Faisal Al Mohareb, MD14*, Naeem Chaudhri,
MD15*, Aminia Kariminia, PhD16*, Sabine Ivison, PhD17*, Diane L.
Fairclough, PhD18*, Gerald Devins19*, David Szwajcer, MD, FRCPC20,
Stephen Ronan Foley, MD, FRCPC21, Clayton A. Smith, MD, FRCPC22, Tony
Panzarella, M.Sc23*, Holly Margaret Kerr, RN, BSN24*, Kirk R. Schultz,
MD25 , and Marc Lalancette, MD26
Dalhousie University and Capital District Health Authority, Halifax, NS, Canada
Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and
Research Centre, Riyadh, Saudi Arabia
3
Blood and Marrow Transplant Program, Hematology Department, MaisonneuveRosemont Hospital, University of Montreal, Montreal, QC, Canada
4
Medicine, McMaster University, Hamilton, ON, Canada
5
Leukemia and Bone Marrow Transplantation Program of BC, British Columbia Cancer
Agency, Vancouver, BC, Canada
6
Section of Hematology and Medical Oncology, CancerCare Manitoba, Dept of Internal
Medicine, University of Manitoba, Winnipeg, MB, Canada
7
Allogeneic Blood and Marrow Transplant Program, Princess Margaret Hospital, University
of Toronto, Toronto, ON, Canada
8
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
9
The Royal Melbourne Hospital, Parkville, Australia
10
Auckland City Hospital, Auckland, New Zealand
11
Directorate of Hematology and Centre for Cancer Biology SA Pathology, Adelaide, Australia
12
University of Ottawa, Ottawa, ON, Canada
13
London Health Sciences Centre, London, ON, Canada
14
King Faisal Specialist Hospital, Riyadh, Saudi Arabia
15
Adult Hematology/HSCT Section, King Faisal Cancer Center, King Faisal Specialist
Hospital, Riyadh, Saudi Arabia
16
Pediatric Hematology/Oncology/BMT, BC Children’s Hospital, Vancouver, BC, Canada
17
Div. Pediatric Hem./Onc./ BMT, BC Children’s Hospital, Vancouver, BC, Canada
18
University of Colorado Anschutz Medical Campus and Colorado School of Public Health,
University of Colorado, Denver, CO
19
University of Toronto, Toronto, ON, Canada
20
CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada
21
Department of Pathology, McMaster University, Hamilton, ON, Canada
22
Division of Hematology, Hematologic Malignancies, University of Colorado AMC, Aurora, CO
23
Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada
24
Vancouver General Hospital, Vancouver, BC, Canada
25
B.C. Children’s Hospital, University of British Columbia, Vancouver, Canada
26
L’Hôtel De Québec, Québec City, Québec, Canada
1
2
Background
Conclusions
This evaluation of rituximab maintenance treatment every 2 mos for
24
one year after ASCT for aggressive lymphoma failed to meet the study
endpoint of improved EFS, compared to observation.
We completed a randomized trial comparing G-PB with G-BM in sibling
allografts for hematologic malignancies (Couban et al, ASH, 2013) and
report the association of allograft cell counts with hematologic recovery
and cGvHD and the pattern of organ-specific cGvHD.
Methods
A phase III randomized trial of matched sibling G-PB vs G-BM allografts
in adults with hematologic malignancies was conducted. The primary
endpoint was time to treatment failure defined as the first occurrence
of extensive cGvHD, disease progression/relapse or death. Adaptive
stratification (minimization) balanced treatment arms by centre,
disease, early vs late disease and conditioning. Donors received G-CSF
5 g/kg/d sc for 4 or 5 days with apheresis on Day 5 and, if necessary,
Day 6 or BM harvest on Day 5. Recipients between 16 and 65 years
received myeloablative conditioning and cyclosporine/methotrexate as
GvHD prophylaxis.
Results
230 sibling donor-recipients were randomized; 7 were unevaluable.
Indication for allograft was AML (109; 49%), ALL (57; 25%); MDS/
MPD (31; 14%), CML (13; 6%), lymphoproliferative disorder(12; 5%)
and biphenotypic leukemia (1). Median total nucleated cells (TNC)/kg
were 7.59x108 (range: 2.73-18.64) and 5.92x108 (range: 0.94-13.23)
in the G-PB and G-BM arms (P<0.0001). Median CD34 cells/kg were
5.50x106 (2.03-23.94) and 3.22x106 (0.29-8.71) (P<0.0001). At a
median follow-up of 36 months (range 9.6-48), using Cox proportional
hazards multivariable modelling adjusted for the 4 minimization factors,
time to treatment failure did not differ significantly between arms (HR
0.91; 95% CI 0.68-1.22; P= 0.52). There was also no OS difference (3year OS 56.8% vs 60.4%; G-PB vs G-BM; p=0.90).
Outcome
G-PB
G-BM
p-value
Grade II-IV aGvHD
19.7% (SE
3.9%)
15.1% (SE 3.4%)
0.43
Grade III-IV aGvHD
9.9% (SE 3%)
3.8% (SE 1.9%)
0.09
Any cGvHD by 2 yrs
80.9% (SE
4.5%)
68.4% (SE 5.1%)
0.03
Extensive cGvHD
by 2 yrs
67.1% (SE
5.0%)
59.9% (SE 5.0%)
0.15
Neutrophil recovery,
17 (10-32)
median d (range)
20 (12-38)
<0.004
Platelet recovery,
median d (range)
21 (9-64)
<0.0001
18 (5-91)
Neutrophil and platelet recoveries were related to CD34 cells/kg in G-PB
(neutrophils: regression slope (RS) -0.39; platelets: RS -0.21) and G-BM
(neutrophils: RS -0.93; platelets RS -0.49). There was no correlation of
CD34 cells/kg or TNC/kg with overall or extensive cGvHD. More hepatic
cGvHD was reported with G-PB.
Conclusions
In this large, randomized trial, there were no differences in time to
treatment failure, overall survival or cumulative incidence (CI) of
aGvHD, overall or extensive cGvHD despite substantive differences in
cellular composition of the allografts. Correlation of CD34 cell dose with
hematologic recovery is expected. The finding of no difference in the
CI of overall and extensive cGvHD between the two arms, despite the
anticipated 10-fold difference in T-cell dose and the lack of correlation
between CD34 cell dose and cGvHD suggest that factors other than
T-cell and CD34 dose must affect the likelihood of developing cGvHD.
Use of G-CSF as a mobilizing agent may increase the likelihood of
developing cGvHD more than has been appreciated.
03. Plasma Levels Of Mitochondrial DNA
(MtDNA) Are Able To Stimulate B Cells To
Produce Proinflammatory Cytokines And
Are Increased At The Onset Of Chronic
Graft Versus Host Disease
Ivison S1, Kariminia A1, Sung S1, Leung V1, Cote H1,Schultz KR1
BC Children’s Hospital, Child and Family Research Institute, University of British Columbia
1
Background
During hematopoietic stem cell transplantation (HSCT) there are a
number of factors that contribute to recipient cell damage including
cytotoxic agents and alloimmunity associated with cGVHD. Previously,
our group was the first to describe an activated memory B cell phenotype
with an exaggerated response to TLR9 agonists associated with the
onset of extensive cGVHD. TLR9 agonists usually are from bacterial
single stranded DNA although another TLR9 agonist may be human
mitochondrial DNA (mtDNA). Plasma mtDNA have been reported to
increase after injury or trauma with cellular release from necrotic cells.
It is likely that recipient cellular damage results in increased plasma
concentrations of immunostimulatory damage-associated molecular
patterns including mtDNA. We hypothesized that plasma mtDNA levels
will be increased in patients with cGVHD compared to patients post
transplant that do not develop cGVHD and that increased mtDNA result
in B cell activation.
Methods
Thirteen patients with cGVHD, 17 post HSCT patients without cGVHD,
and 30 non transplant controls were evaluated. Mitochondrial DNA
concentrations were measured in the plasma by real-time PCR using
specific primers COX1. Briefly, a plasmid containing the COX1 region
amplified by the COX primers was used as standard, each plate
contained a standard with a known number of plasmid copies in serial
dilutions. Copy number was determined by Ct comparison to standard.
In order to accommodate for immune reconstitution in the analysis,
25
patients with cGVHD onset < 9months (early onset) post BMT were
compared to patients without cGVHD measured at 6 months post HSCT
and patients with a late onset of cGVHD were compared to 12 month
post HSCT controls. In addition, we evaluated the ability of mtDNA
derived from an ALL cell line (679) to stimulate B cells isolated from
15 healthy individuals. Up-regulation of co-stimulatory molecules and
proinflammtory cytokine production including IL-6 and TNFwere
investigated in vitro.
Results
It was shown that mtDNA isolated from cell line 697 is able to upregulate expression of co-stimulatory molecules and secretion of proinflammatory cytokines, IL-6 and TNFα, by human B cells. We found
that mtDNA concentrations in plasma was increased in all HSCT
patients compared to non HSCT controls (p<0.0001). It was also found
that mitochondrial DNA plasma concretions were significantly higher in
patients at onset of early and late cGVHD compared to the plasma of
patients at 6 and 12 months post transplant with no cGVHD (p<0.02).
Conclusion
Our findings confirm that mtDNA are able to activate B cells. We
show that although all patients post HSCT have higher concentrations
of mtDNA, that the highest concentrations of mtDNA are associated
with cGVHD. Although further investigation are required to establish a
direct linkage of mtDNA to TLR9 mediated activation of B cells, these
data support the hypothesis that this may be one of the mechanisms
leading to the exaggerated B cells response resulting in autoimmunity
and cGVHD.
04. Cognitive functioning as a predictor
of medication management ability among
stem cell transplant recipients
Mayo S 1, Metcalfe K 1, Messner H 2,3, Rourke S 3,4, Howell D 1,2
Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, 2 Department of
Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, 3 The Ontario HIV
Treatment Network, Toronto, 4Department of Psychiatry, University of Toronto, Toronto, 5
University Health Network, Toronto
1
Objective
To investigate the impact of cognitive functioning on medication
management ability among patients treated with allogeneic stem cell
transplantation.
Rationale
A growing body of evidence suggests that patients with hematological
cancers may experience impairments in cognitive functioning,
particularly after treatment with stem cell transplantation. However, the
real-world implications of such deficits are unclear. Research conducted
across non-cancer clinical settings suggests that cognitive impairments
26
may reduce the ability to manage medications effectively. Given that
adherence to complex medication regimens is essential for minimizing
medical complications after stem cell transplantation, the relationship
between cognitive functioning and medication management ability in
this population was investigated.
Methodology
As part of a longitudinal study of cognitive functioning following
allogeneic stem cell transplantation, transplant recipients were invited
to complete a standardized battery of cognitive tests prior to transplant,
at Day 100 and six months post-transplant. This battery included
neuropsychological tests of learning and memory, processing speed
and psychomotor efficiency, and executive functioning and working
memory. To measure medication management ability at each time
point, participants also completed a task in which they were asked to
dispense and make inferences about a simulated medication regimen.
Finally, socio-demographic, medical, and symptom characteristics
were collected through chart abstraction and self-administered
questionnaires. Eligible participants were English-speaking adults
receiving their first allogeneic stem cell transplant. Non-linear multilevel modeling was used to compare participants who met the criteria
for impaired medication management ability to those who were not
impaired, on cognitive functioning and various confounders.
Results
56 participants who completed baseline study measures as well as at
least one follow-up visit (Day 100 and/or six months) were included
in the analysis. 46% (26/56), 38% (19/50) and 29% (12/42) met the
criteria for cognitive impairment at baseline, Day 100 and six months,
respectively. 43% (24/56), 40% (19/48) and 36% (15/42) had impaired
medication management ability at baseline, Day 100 and six months,
respectively. At each time point, greater severity of cognitive impairment
was significantly correlated with worse medication management ability.
Based on non-linear multi-level models, specific cognitive abilities that
predicted impaired medication management ability were identified
overall and at each time point. In particular, worse performance in
the domain of executive functioning and working memory consistently
predicted impaired medication management ability, even when
controlling for confounders, such as pre-morbid IQ and conditioning
intensity. Depressive symptoms, fatigue or physical symptom distress
were not significant predictors of impaired medication management
ability at any time point.
Conclusion
While medication adherence can depend on a range of factors, these
findings suggest that poor cognitive functioning, particularly in the area
of executive functioning and working memory, may affect patients’
ability to manage medications within the first six months of transplant.
05. Utilization of Unrelated Hematopoietic
Stem Cell products cryopreserved at the
time of Allogeneic Stem Cell Transplant
Rishi Agarwal1, Lois Ayash,2 Abhinav Deol,2, Lawrence Lum,2 Voravit
Ratanatharathorn,2 Joseph Uberti,2 Muneer H. Abidi,2
University of Cincinnati, Cincinnati, Ohio, USA-45229
Wayne State University/Karmanos Cancer Center, Detroit, Michigan, USA- 48201
1
2
Background
The optimal dose of CD34+ hematopoietic stem cells (HSC) for
allogeneic stem cell transplant (SCT) is not well defined. Reports exists
that higher CD34+ cell dose is associated with better engraftment
and may increase the risk of GVHD. In the absence of clear guidelines,
it is unclear if transplant centers infuse the entire HSC product or
cryopreserve the surplus dose. To the best of our knowledge, there
is no data regarding the practice of cryopreservation in the setting
of allogeneic SCT. We designed a retrospective study to analyze the
clinical, ethical and economical aspects of cryopreservation of unused
HSC after an allogeneic SCT.
Methods
Wayne State University institutional review board approved this
retrospective study. Patients >18 years, who received unrelated
peripheral HSC between January 1, 2000 and July 1,2010 were included
in the analysis.
Results
Total 360 unrelated allogeneic SCTs were performed and a portion
of HSC was cryopreserved in 43 of 360 patients. These patients were
included in the analysis. Patient demographics: M/F-25/18, median age
at transplant was 48 (range 18-67) years, median Karnofsky score was
90% (range 60-90). Twenty two out of forty three patients (52%) were
alive at the time of analysis. Diagnosis included acute myelogenous
leukemia (n=19) (44%), acute lymphoblastic leukemia (n=9) (20%),
non-Hodgkin’s lymphoma (n=8) (18%), myelodysplatic syndrome
(n=4), and chronic lymphocytic leukemia (n=3). Median number of
stem cells acquired was 15.9 (1.87-44.33) X 106 cells/kg. Median stem
cells infused were 8.03 (range 1.33-14.68) X 106 cells/kg. The median
volume of stem cell product used was 175 (range 85.8-454) ml. Median
stem cells unused and cryopreserved were 7.68 (range0.54-29.95) X
106 cells/kg, and the median volume cryopreserved was 300(range 100600) ml. The median day of platelet engraftment (n=37) was 17(range
0-321) days, and median day of white blood cells engraftment (n=42)
was 11 (range 0-13) days. In terms of post-transplant course, incidence
of grade I-IV acute graft versus host disease (GVHD) was 29/43(67%).
The median day of occurrence of acute GVHD was 26 (range 3-91)
days. Median duration for HSC cryopreservation till this analysis was
364(range 211-546) weeks. The cryopreserved HSCs were not reused
for a second transplant in any patient.
Conclusion
In our analysis the cryopreserved surplus HSCs were never used for
a second transplant. No specific guidelines exist regarding the use
of surplus related or unrelated HSCs which are being cryopreserved
indefinitely. The cryopreservation of these HSCs is an ethical as well as
economic and logistic concern for institutions involved in this practice
and specific guidelines need to be developed in this regard.
27
Poster Abstract Index
Poster group 1: Pharmacy, Nursing, and Laboratory Abstracts
Thursday, June 12, 2014 | 4:00pm – 4:15pm • Commonwealth Ballroom
#
Title
Presenting Author
1
THE UBC STEM CELL CLUB: IMPROVING THE QUALITY AND QUANTITY OF MEMBERSHIP ON CANADA’S
STEM CELL DONOR DATABASE
Warren Fingrut, MD
2
IMMUNIZATIONS POST-HCT: A CROSS-CANADA EVALUATION
Laura McGillis, BSc, RN
3
TRANSITIONING FROM PEDIATRIC TO ADULT CARE POST ALLOGENEIC HSCT: A QUALITY IMPROVEMENT
INITIATIVE
Laura McGillis, BSc, RN
4
THE IMPACT OF MATCHING PATIENTS NEEDS TO NURSING RESOURCES: LESSONS LEARNED FROM
APPLYING THE SYNERGY MODEL IN A HEMATOLOGY/HSCT UNIT
Yayra Amenudzie, RN
5
BONE LOSS IS SEEN AS EARLY AS 100 DAYS IN PATIENTS POST ALLOGENEIC HEMATOPOIETIC STEM CELL
TRANSPLANT
Raewyn Broady, MD
6
MULTIDISCIPLINARY CARDIO-ONCOLOGY REVIEW PRIOR TO AUTOLOGOUS SCT
Nanette Cox-Kennett, MN
7
EVALUATING THE BENEFITS OF TRANSITIONING FROM INTRAVENOUS TO SUBCUTANEOUS RITUXIMAB
FOR ALBERTA CANCER PATIENTS
Cherie C. Severson, RN,
8
28
EXTRACORPOREAL PHOTOPHERESIS IN A pediatric AMBULATORY SETTING: ESTABLISHING A NURSING
PROTOCOL FOR CARE
Candidate
MN, CON(C)
Christine Armstrong, RN
(EC), NP
9
IDENTIFICATION AND MANAGEMENT OF GLUCOCORTICOID-INDUCED HYPERGLYCEMIA ON A BONE
MARROW TRANSPLANT WARD: A QUALITY IMPROVEMENT INITIATIVE
Andrew Aw, MD, CM, MEng
10
COUNT RECOVERY AND VIABILITY AFTER SERIAL REFREEZING OF CRYOPRESERVED STEM CELL GRAFTS
Nazir Jamal
11
COLLECTION EFFICIENCY IN STEM CELL COLLECTIONS: EXPLORING FACTORS AFFECTING COLLECTION
EFFICIENCY
Eduard Cojocari
12
ENUMERATION OF CD34+ CELLS USING AN ACCURI C6 CYTOMETER
Susie Joron
13
ANTIMICROBIAL ACTIVITY IN CORD BLOOD UNITS: OCCURRENCE AND LEVELS OF ANTIBIOTICS
Susie Joron
14
OPTIMIZING THE USE OF G-CSF FOLLOWING AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT
FOR HEMATOLOGIC MALIGNANCIES: AN ANALYSIS OF CANADIAN PRACTICE
Christopher Hillis, MD, BSc
15
INFECTION PREVENTION AND CONTROL RELATED TO RESPIRATORY VIRAL ILLNESS IN HEMATOPOIETIC
STEM CELL TRANSPLANT (HSCT) RECIPIENTS: THE OTTAWA HOSPITAL EXPERIENCE FROM 2008-2012
Carey Landry, BSc, PhD
16
THE HEMA-QUEBEC PUBLIC CORD BLOOD BANK (CBB): DISTRIBUTION AND CLINICAL OUTCOMES OF
TRANSPLANTED UNITS
Susie Joron
17
HUMAN ALBUMIN EYE DROPS IS SAFE AND EFFECTIVE ALTERNATIVE FOR THE INDICATION OF
KERATOCONJUNCTIVITIS SICCA SECONDARY TO GVHD POST ALLO-STEM CELL TRANSPLANTATION
Jack T. Seki, RPh, BSc (Phm),
PharmD
Poster Group 2: Basic and Translational Research Abstracts
Friday, June 13, 2014 | 10:00am – 10:20am • Commonwealth Ballroom
#
Title
Presenting Author
18
EFFECTS OF IONIZING RADIATION ON MESENCHYMAL STEM CELLS IN PATIENTS WITH AML:
IMPLICATIONS FOR TBI-BASED HEMATOPOIETIC CELL TRANSPLANTATION STRATEGIES
Yevgeniya Le, PhD
19
MESENCHYMAL STROMAL CELL TREATMENT IN XENOGENEIC CHRONIC GRAFT-VERSUS-HOST DISEASE
MOUSE MODEL
Hisaki Fujii, MD, PhD
20
MAJOR ABO INCOMPATIBLE BONE MARROW TRANSPLANTATION IN CHILDREN: DETERMINING WHAT
RESIDUAL VOLUME OF DONOR RED CELLS CAN SAFELY BE INFUSED FOLLOWING RED CELL DEPLETION
MD
ANTIBIOTIC PROPHYLAXIS THERAPY FOR PATIENTS UNDERGOING HEMATOPOIETIC STEM CELL
TRANSPLANT: A TALE OF 2 CENTERS
MD
21
22
CD8+ T-LYMPHOCYTES FROM PEDIATRIC RECIPIENTS OF BONE MARROW OR UMBILICAL CORD BLOOD
TRANSPLANTATION EXPRESS DIVERSE ASSORTMENTS OF INHIBITORY RECEPTORS AT THEIR SURFACE IN
THE EARLY POST-TRANSPLANT PERIOD
Tal Schechter-Finkelstein,
Tal Schechter-Finkelstein,
Insaf Salem Fourati, Ing,
MSc
23
PATHOGEN-SPECIFIC T-CELL LINE GENERATION FOR THE TREATMENT OF VIRUS-RELATED COMPLICATIONS Jean-Sébastien Delisle,
MD, PhD
AFTER TRANSPLANTATION
24
IMPAIRED INTERFERON-ALPHA PRODUCTION BY PLASMACYTOID DENDRITIC CALLS AFTER CORD BLOOD
TRANSPLANTATION: IMPLICATION FOR POST-TRANSPLANT TLR-LIGAN BASED IMMUNOTHERAPY
Paulo Cordeiro, MSc
25
CANADIAN PILOT CLINICAL TRIAL: LENTIVIRUS-MEDIATED GENE THERAPY FOR ADULT FABRY DISEASE
Ronan Foley, MD, FRCPC
26
EFFECT OF G-CSF STIMULATION ON DONOR BLOOD PARAMETERS FOLLOWING PBSC DONATION: A
ONEMATCH PILOT STUDY
Karena Volesky
27
DEVELOPING EDUCATIONAL RESOURCES TO ADVANCE ETHICAL UMBILICAL CORD BLOOD RESEARCH: A
CANADIAN PERSPECTIVE
Sophie Chargé, PhD
Poster Group 3: Clinical Trials and Observations Abstracts
Friday, June 13, 2014 | 3:30pm – 4:00pm • Commonwealth Ballroom
#
Title
Presenting Author
28
POLYCLONAL HUMAN INTRAVENOUS IMMUNE GLOBULIN (IGIV) WITH HIGH-LEVELS OF RSV
NEUTRALIZING ANTIBODIES: A SUMMARY OF ANIMAL AND HUMAN STUDIES
James Mond
29
AN ASSESSMENT OF THE OUTCOMES OF SECOND DONATION REQUESTS THROUGH THE CANADIAN
ONEMATCH UNRELATED REGISTRY
Iain Arseneau, BSc (Hons)
30
INTERACTIONS BETWEEN ALEMTUZUMAB AND CYTOMEGALOVIRUS SEROSTATUS OF RECIPIENT IN
UNRELATED DONOR TRANSPLANT FOR MYELOID MALIGNANCIES
Mohamed Shanavas, MD
31
MULTICENTER CLINICAL STUDY TO ASSESS ORAL COMPLICATIONS OF CONDITIONING THERAPY AND
STEM CELL TRANSPLANTATION- ORASTEM STUDY
Firoozeh Samim, DMD, MSc
32
MYELOABLATIVE BUSULFAN CONDITIONING REGIMENS: SINGLE CENTER EXPERIENCE OF PATIENTS WITH
MYELOID NEOPLASMS
Renju V. Raj, MD
33
PROFILING STUDY CHARACTERISTICS IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION: A
LIMITED SCOPING REVIEW
Sophie Pilon
29
34
PROJECT COBRA: COMPENDIUM OF BEST EVIDENCE FROM RCTS IN ALLOGENEIC HEMATOPOIETIC CELL
TRANSPLANTATION
David Allan, MD, FRCPC
35
A SYSTEMATIC REVIEW OF PRECLINICAL STUDIES ON THE THERAPEUTIC POTENTIAL OF MESENCHYMAL
STROMAL CELL-DERIVED MICROVESICLES
David Allan, MD, FRCPC
36
CHRONIC GRAFT-VERSUS-HOST DISEASE IS A SIGNIFICANT RISK FACTOR FOR THE DEVELOPMENT OF
NOCARDIOSIS IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: A MATCHED CASE- Nadia Bambace, MD, FRCPC
CONTROL STUDY OF RISK FACTORS, CLINICAL FEATURES, AND OUTCOMES
37
SERUM ALBUMIN LEVEL < 32 G/L ON DAY 30 CAN PREDICT HIGHER RISK OF NON-RELAPSE MORTALITY
IN ACUTE LYMPHOBLASTIC LEUKEMIA FOLLOWING ALLOGENEIC STEM CELL TRANSPLANTATION
Feras Alfraih, MD
38
VALIDATION OF FAVOURABLE IMPACT OF LARGE GRANULAR LYMPHOCYTOSIS AFTER ALLOGENEIC
Marc Poch Martell, MD
39
NEPHROTIC RANGE PROTEINURIA AS A POSSIBLE MANIFESTATION OF CHRONIC GRAFT-VERSUS-HOST
DISEASE
Renju V. Raj, MD
Saturday, June 14, 2014 | 9:55am – 10:10am • Fundy Room
#
Title
Presenting Author
40
IMPORTANCE OF MONITORING COMPLETE MOLECULAR REMISSION IN PEDIATRIC ACUTE MYELOID
LEUKEMIA BEARING MLL REARRANGEMENTS: FOCUS ON THE RARE AND NOT ALWAYS “GOOD
PROGNOSIS” T(1;11)(Q21;Q23) TRANSLOCATION
Lucie Pécheux, MD
41
RELAPSE AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION FOR AGGRESSIVE NHL: CLINICAL
CHARACTERISTICS AND FACTORS PREDICTING OUTCOME
Shane Gangatharan, MD
42
ISOLATED PENILE MEATAL CHRONIC GVHD IN A BOY FOLLOWING ALLOGENEIC TRANSPLANT FOR JMML
Carol Spicer, RN, BN
43
ESCALATED DOSE-TOTAL BODY IRRADIATION (18GY) FOLLOWED BY AN ALLOGENEIC CELL
TRANSPLANTATION FOR THE TREATMENT OF REFRACTORY ACUTE MYELOID LEUKEMIA: EARLY RESULTS
Sultan Altouri, MD
44
PRE-TRANSPLANT REMISSION STATUS AND USE OF PERIPHERAL BLOOD STEM CELLS CONTRIBUTE TO
LONG-TERM OUTCOME AFTER MYELOABLATIVE ALLOGENEIC TRANSPLANT FOR MULTIPLE MYELOMA
Imran Ahmad, MD
Saturday, June 14, 2014 | 3:00pm – 3:15pm • Fundy Room
30
#
Title
Presenting Author
45
AN EXPLORATION FOR A MINIMUM CD34+ DOSE FOR MULTIPLE MYELOMA PATIENTS AGED 65 TO 71
BASED ON AN ASSOCIATION BETWEEN CD34+ DOSE AND LONG-TERM PLATELET COUNTS FOLLOWING
HIGH DOSE THERAPY
Ronan Foley, MD, FRCPC
46
WHEN AN UNEXPECTED EVENT CHANGES TRANSPLANT INTO FAITH: THE UNTOLD STORY OF CBMTG
0601
Imran Ahmad, MD
47
HIGH PROGRESSION-FREE SURVIVAL AT 10 YEARS AFTER TANDEM AUTOLOGOUS/NONMYELOABLATIVE
ALLOGENEIC TRANSPLANT FOR MULTIPLE MYELOMA: IMPACT OF DISEASE STATUS AND CHRONIC GVHD
Imran Ahmad, MD
48
PSEUDOTUMOR CEREBRI ASSOCIATED WITH ALL-TRANS RETINOIC ACID TREATMENT IN FEMALE
PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA: A CASE SERIES
Mohamed Ali, PharmD
49
50
POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME ASSOCIATED WITH CYCLOSPORINE USE IN A
CHILD UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM CELLS TRANSPLANTATION FOR FANCONI
ANEMIA: A CASE REPORT
Mohamed Ali, PharmD
FIRST LINE TYROSINE KINASE INHIBITORS (TKIS) THERAPY IN CHRONIC MYELOID LEUKEMIA AT THE
CANCER PROGRAM OF WINDSOR REGIONAL HOSPITAL (2001-2013)
Caroline Hamm, MD
Non-Presenting Abstracts
#
Title
Topic
Author
51
ENHANCING HEALTHCARE PROFESSIONALS AWARENESS AND
UNDERSTANDING OF PSYCHOSOCIAL DISTRESS AMONG SPOUSAL
CAREGIVERS OF HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: A
ROLE FOR DIGITAL STORIES AND ILLNESS NARRATIVES
Pharmacy, Nursing, and
other transplant support
52
EXPLORING THE CONCEPT OF WAITING AMONG SPOUSAL CAREGIVERS OF
HSCT PATIENTS: THE BETWIXT AND BETWEEN
Brenda Sabo, RN, PhD
53
THE EXPERIENCE OF SEXUALITY IN INDIVIDUALS WHO HAVE UNDERGONE
Reanne Booker, MN, BScN
54
THE DEVELOPMENT OF AN ADULT BLOOD AND MARROW TRANSPLANT
SURVIVORSHIP CLINIC
Reanne Booker, MN, BScN
Brenda Sabo, RN, PhD
1. THE UBC STEM CELL CLUB: IMPROVING THE QUALITY
AND QUANTITY OF MEMBERSHIP ON CANADA’S STEM
CELL DONOR DATABASE
training emphasizing target demographics and informed consent.
Results were compiled from post-event reports.
Fingrut W, Charman E., Sokalski K, McIntyre M, Boudreau K, Hicks R,
Li C, Subedi M
We have coordinated 21 stem cell drives and recruited 2309 potential
stem cell donors. Our university drives in Metro Vancouver, Victoria,
Prince George, and Kelowna have signed up 1191, 434, 95, and 87
registrants respectively. Our community drives have recruited 457
registrants. From November 2012-February 2014, 73.5% of the 1212
registrants recruited at our university drives were male. From October
2013-February 2014, of the 118 males recruited at our university drives,
34.7% self-reported as non-Caucasian and 86.4% were under age 25.
Our rural drives recruited 28 Aboriginal males under age 35, increasing
the representation of this demographic group on Canada’s database by
up to 5.5%.
University of British Columbia, Vancouver, BC, Canada
Background
Many patients with blood diseases require a hematopoietic stem cell
transplant as part of their treatment, and frequently rely on unrelated
donors. Canada’s stem cell donor-database is used to match potential
donors to patients in need. Individuals age 17-35 can register to join
this database online or at stem cell drives, where they provide consent
and swab their cheeks to provide a tissue sample.
Patients are more likely to match to a donor in their own ethnic group.
Additionally, young, male donors are preferred, as they improve
recipient outcomes. However, males under age 35 only represent 12%
of the current Canadian donor-database (5% non-Caucasian males).
The UBC Stem Cell Club was founded two years ago, aiming to increase
membership on the stem cell donor-database and address the need for
young, ethnically-diverse, and male registrants.
Results
Conclusion
The UBC Stem Cell Club recruits Canadians to become stem cell donors.
Our drives improve the quantity and quality of membership on Canada’s
stem cell donor-database.
Methods
The UBC Stem Cell Club is a community partner of OneMatch. We
run stem cell drives across British Columbia. Our volunteers complete
31
2. IMMUNIZATIONS POST-HCT: A CROSS-CANADA
EVALUATION
McGillis L1, Deotare U1, Kumar D1,2, Seftel M1,2
Princess Margaret Cancer Centre, and 2 The University of Toronto
1
Introduction
L Mcgillis 1, C Armstrong2, A Gassas2,3, A Gascadi2, S Courtney2, J
Lowry2
1
Immunization of recipients of HCT is an important element of posttransplant care. Despite the existence of national guidelines, the
approach to post HCT immunization in Canadian HCT centres is
unknown. Our goal was to understand the type, timing and uptake of
vaccinations being provided to Canadian HCT recipients.
Main Thesis
We performed a survey of post HCT immunization schedules from all
Canadian HCT centres. We asked for details of (1) type and schedule of
vaccines (2) logistics of vaccine administration (3) proportion of patients’
actually receiving vaccination, and (4) suggestions for improvement in
practice. We compared Canadian HCT centre immunization schedules
with guidelines from the CDC (2013), EBMT (2012) and NACI (2013).
Summary
Surveys were returned from 10/13 (77%) HCT centres. In general,
immunization timing and choice of vaccine fell within recommended
guidelines. Recommendations for Meningococcal, HPV, and
Varicella vaccines varied between centres. All centers recommended
pneumococcal vaccines although timing of Pneumococcal vaccines
varied more frequently between centres than other vaccines. Most
immunizations were given by family physicians or the community
health team. The majority of centres provided patients with a letter
and schedule asking the patient to assume responsibility of receiving
vaccines. Most centres reported having a poor understanding of how
many of their patients were receiving immunizations. Funding of
vaccines from a provincial level varied amongst centres which may
account for variations in practice. Vaccination practices were similar to
recommendations by CDC/EBMT/NACI.
Conclusion
We found substantial variation in post HCT immunization practice at
Canadian HCT centres. The measurement of vaccine uptake remains a
challenge for most HCT centres. As vaccine preventable diseases pose
a threat to the health of HCT recipients and represent a public health
priority in Canada, we recommend the development of uniform vaccine
schedules, reimbursement practices, and measurement of immunization
compliance.
32
3. TRANSITIONING FROM PEDIATRIC TO ADULT CARE
POST ALLOGENEIC HSCT: A QUALITY IMPROVEMENT
INITIATIVE
3
Princess Margaret Cancer Centre, Toronto; 2The Hospital for Sick Children, Toronto, and
The University of Toronto
Introduction
Princess Margaret Cancer Centre (PMC) and The Hospital for Sick
Children (HSC) teamed up to improve pediatric to adult transition for
adolescent HSCT survivors and identify late health effects for adolescents
post -HSCT.
Thesis
Adolescents post allogeneic HSCT often have chronic and complex
medical needs and unique challenges navigating the health care system
as they transition from pediatric to adult health care models. PMC and
HSC worked to improve transition care by identifying gaps in the current
transition model, identifying common medical concerns for adolescents
post-HSCT and an assessing how and why patients are lost during
transition.
Summary
Since 2005, 27 patients transitioned from HSC to PMC. Ongoing health
care needs include osteopenia, AVN, secondary malignancy, endocrine
dysfunction, and significant chronic GVHD requiring therapy amongst
others. Through a review of charts we discovered 19% of patients were
lost to follow-up during the currently practiced transition process. Needs
assessment led to development of check-lists of important information
to be sent from HSC to PMH, receiving and reviewing of referrals by
Nurse Practitioner, education pamphlets for patients and families,
earlier discussions with patients regarding transition, and in-hospital
meetings with patients at HSC prior to transition. These initiatives led to
improved communication between HSC and PMC, fewer clinic visits for
patients, and no patients lost to follow up for their initial appointment
since starting the new transition process.
Conclusion
Childhood HSCT survivors are at risk of developing late complications
post-HSCT. Patients must remain closely monitored by a transplant
specific team to assess and treat late effects as they occur. Poorly
transitioned adolescents may be less likely to follow-up with the
transplant team leading to inappropriate management of long-term late
complications post-HSCT. Our new transition model aims to solidify and
improve patient transition leading to improved satisfaction and overall
quality of care of adolescent HSCT survivors.
4. THE IMPACT OF MATCHING PATIENT NEEDS TO
NURSING RESOURCES: LESSONS LEARNED FROM
APPLYING THE SYNERGY MODEL IN A HEMATOLOGY/HSCT
UNIT
5. BONE LOSS IS SEEN AS EARLY AS 100 DAYS IN
PATIENTS POST ALLOGENEIC HAEMATOPOIETIC STEM CELL
TRANSPLANT
Amenudzie, Y , O’Sullivan L , Georgiou G , Ho E , Heelam E,
1
. Leukemia/BMT Program of British Columbia, 2. Department of Medicine, University of
British Columbia 3. Prohealth Clinical Research Centre
1
1
1
2
1
Hematology/Hematopoietic Stem Cell Transplant Program, Juravinski Hospital and Cancer
Centre, Hamilton Health Sciences, 2Performance & Improvement, Hamilton Health Sciences
1
Introduction
The Hematology/Hematopoietic Stem Cell Transplant (HSCT) Program at
the Juravinski Hospital and Cancer Centre identified a unique opportunity
to enhance patient care and the work environment by piloting the
Synergy Model (Curly, 2007), a professional practice framework which
involves assessing patient acuity and making assignments based on a
“fit” between patient needs and staff competency. Published research
suggests the models’ patient-centered philosophy optimizes patient
outcomes, enhances collaboration and teamwork around the common
goal of better care provision, provides a unified language for discussing
care and measuring patient acuity, helps teams make objective decisions
about staffing assignments, and helps administrators establish staffing
levels for effective patient care and workload management. The model
has been shown to be beneficial in various health care settings, but has
yet to be applied with a hematology/HSCT patient population.
Thesis
A pilot project was undertaken to examine the adaptability, applicability,
and effectiveness of the Synergy Model in a Canadian inpatient
hematology/HSCT setting.
Summary
A previously developed toolkit was used to build a hematology/
HSCT patient acuity tool which measures patient complexity, stability,
predictability, and participation in care. An interrater reliability analysis
of the tool revealed high internal consistency (4 items, α > 0.7) and
moderate rater agreement(Kappa= 0.68, p <.05). A nurse competency
assessment was developed using the Canadian Association of Nurses in
Oncology practice standards. Processes were created for scoring patient
acuity, making patient assignments, and for making decisions about
staffing levels. The tool and processes were piloted starting in October
2013.
Conclusion
The Synergy model can be adapted and applied to a hematology/HSCT
population. We will share the processes used to adapt and implement
the model as well as key enablers and barriers to implementation. By
April 2014 we will have a detailed analysis of the model’s impact on the
unit. These findings will be presented.
Pajerksi, B. 1, Broady, R.1,2, Kendler D. 2,3 University of British Columbia
Introduction
Bone loss is a common complication for survivors of allogeneic
haematopoietic stem cell transplant (HSCT); osteoporosis is reported in
up to 50% of transplant recipients. Multiple risk factors contribute to
bone loss including chemotherapy, radiotherapy, GVHD, gonadal failure
and glucocorticoid use. Older age, poor nutrition, weight loss and
physical inactivity also increases the risk for declines in bone mineral
density (BMD) in this population. Previous studies have demonstrated
that bone loss occurs within the first 6-12 months after HSCT; the
appropriate time to initiate BMD testing is not known. Delay in BMD
testing may delay needed preventative strategies in patients who may
already have or be at risk for osteoporosis.
Aim
Few studies have addressed early changes in BMD in the 100 days
post HSCT. BMD testing before and early after HSCT could identify both
patients with low pre-existing bone density and those with rapid loss
post transplant and allow for early interventions to prevent or reverse
bone loss.
Methods
We reviewed charts of patients who underwent an allogeneic HSCT
between 2011 and 2013. BMD was measured at the lumbar spine, total
hip, and femoral neck using dual energy x-ray absorptiometry (DXA)
before HSCT and at day 100 post HSCT. Risk factors for osteoporosis
were evaluated, including personal history of fracture, family history of
hip fracture, alcohol, smoking, rheumatoid arthritis, weight changes,
transplant conditioning therapy, and history of steroid use.
Results
A total of 91 patients, 56 male and 35 female were reviewed. Mean
age was 48. The hematologic diagnoses were AML: 35; ALL; 14; CML:
7; CLL: 10; NHL: 9; RAEB: 5; other: 11. At day 100 post HSCT patients
experienced a mean decline of 3.27% ± 4.19% in lumbar spine BMD,
4.43% ± 4.83% in total hip BMD and 4.53% ± 5.25% in femoral neck
BMD (P = < 0.0001 for lumbar spine, total hip, and femoral neck). The
42 patients who received glucocorticiods for GVHD had a significantly
greater decline in BMD at the total hip (5.79% vs. 3.27% p=0.012)
and femoral neck (5.96% vs. 3.27% p=0.015) sites compared to the
patients not receiving glucocorticoids. Weight changes over the first
100 days post transplant were not significantly associated with changes
in BMD. Since least significant change in BMD at a good DXA facility
33
may be around 3%, we queried how many patients had a significant
decline in BMD over the 100 days post transplant. At spine, 46 patients
(50.4%); at total hip 56 patients (61.5%); and at femoral neck 55
patients (60.4%) had a greater than 3% decline.
Discussion
We demonstrate that HSCT recipients have significant declines in both
hip and spine BMD in the 100 days post-allogeneic HSCT. The declines
in femoral sites imply rapid cortical bone loss as well as the expected
trabecular bone loss.. Early detection of changes in BMD may help to
target osteoporosis therapies to patients at the greatest risk of bone loss
and eventual fracture.
6. MULTIDISCIPLINARY CARDIOONCOLOGY REVIEW PRIOR
TO AUTOLOGOUS SCT
Cox-Kennett N1, Paterson I2, 3, Sandhu I1,2, Venner C1, 2, Becher H2, 3,
Pituskin E1, 2.
Cross Cancer Institute, Edmonton AB, 2 University of Alberta, Edmonton AB, 3
Mazankowski Alberta Heart Institute, Edmonton AB
1
Background
Cancer patients (PTS) referred for autologous bone marrow
transplantation (autoBMT) are frequently pre-treated with established
cardiotoxic medications including cyclophosphamide, anthracyclines
and kinase inhibitors. As a result, PTS may not have adequate cardiac
function to meet eligibility criteria for potentially lifesaving autoBMT.
Furthermore, with mobilizing and consolidation chemotherapy, PTS
receive serial exposures to cardiotoxins, with acute and long-term
negative cardiac sequelae. Accordingly, these PTS represent a population
with a major unmet need for appropriate screening and interventions.
Aim: to determine the effects of a prospective multidisciplinary cardiooncology assessment and intervention in an unselected patient
population referred for autoBMT.
Methods
Between January 1, 2013 – December 31, 2013, PTS referred for
autoBMT were systematically screened for comorbid conditions,
cardiovascular risk factors and eligibility for transplant. All underwent
complete physical assessment, laboratory (ECG, complete profile) and
transthoracic echocardiogram with contrast. Those with EF < 50%,
increased IVsd/LVpWd, ECG abnormalities +/- significant cardiac
history also received proBNP and high sensitivity troponin testing.
PTS with abnormal findings or decreased left ventricular (LV) function
were referred to the Edmonton Cardio-Oncology REsearch (ENCORE)
program. ENCORE is a novel multidisciplinary & multispecialty rapidaccess program of oncology, cardiology and allied health disciplines.
34
Results
73 unique PTS were screened by the Edmonton autoBMT program.
Of these, 16 (20%) were reviewed by ENCORE. Reasons for referral
included: decreased LV function (n = 6, 38%); increased IVsd (n = 5,
31%); arrhythmia (n = 4, 25%); angina (n = 1, 5%). Pharmacotherapy
was initiated for 6 PTS; additional modality or serial cardiac imaging
for 12 PTS; urgent stent for 1 PT. 100% of PTS proceeded to autoBMT.
Conclusions
As a result of systematic screening, a high proportion of PTS referred
for autoBMT received assessments and cardio-oncology interventions,
with all PTS subsequently proceeding safely through transplantation.
ENCORE represents a novel approach in the provision of cardiooncology expertise for autoBMT PTS acutely during the mobilizing and
transplantation period. Future examination of our prospective dataset
will elucidate the longer term effects of our interventions.
7. EVALUATING THE BENEFITS OF TRANSITIONING FROM
INTRAVENOUS TO SUBCUTANEOUS RITUXIMAB FOR
ALBERTA CANCER PATIENTS
Cherie C. Severson RN, MN, CON(c). Tom Baker Cancer Center, Calgary Alberta,
Canada.
Introduction
A novel approach to treating cancer in the settings of Non-Hodgkin’s
Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL) is the use
of a subcutaneous (SC) injection of Rituximab (in addition to standard
combination chemotherapy). Currently in Alberta, Rituximab is given
intravenously (IV) in addition to standard combination chemotherapy.
The infusion doses can take hours and patients are at risk for
hypersensitivity reactions.
Main Thesis
Alberta cancer patients can safely benefit from the administration of
subcutaneous Rituximab in numerous ways while still ensuring efficacy
and optimal treatment for their cancer.
Summary
Review of the American literature revealed several studies indicating
the benefits of SC Rituximab. BP22333 Stage 1 (Spark Thera trial)
revealed pharmacokinetic results of Rituximab concentrations on day
28 in NHL patients administered 625mg/m2 SC were comparable to
those in patients administered the standard IV dose of 375mg/m2. A
fixed dose of 1400mg SC Rituximab is expected to achieve non-inferior
C-trough and AUC levels compared with the standard Rituximab IV
dosing of 375mg/m2 for NHL. The SABRINA study reports Rituximab SC
delivers comparable efficacy to IV administration. The results revealed
an ORR 54% (IV+ chemo) versus 57% (SC + chemo); CR 19% vs 29%
respectively and PR 35% versus 37% respectively. The safety profiles
of Rituximab SC and IV are comparable. However the administration
related reactions (ARR) were higher in the SC arm than the IV arm (31%
versus 4% respectively). ARRs reported include local erythema (13%),
local injection site erythema (5%), myalgias (5%), vomiting, puritis
and chills (3-6%). The majority of events were reported as mild and
reversible. The Sawyer B025341 Phase 1b study shows non-inferior
pharmacokinetics and comparable safety profiles of Rituximab SC to
Rituximab IV in CLL patients receiving combination (FC) chemotherapy.
This study further reports a fixed dose of Rituximab 1600mg SC is
non-inferior to 500mg/m2 of Rituximab IV. Although the ARR profile
is higher with the patients who received SC Rituximab, the severity of
the ARRs reported are erythema and transient injection site reaction. A
higher incidence of neutropenia was reported in the patients receiving
Rituximab IV. A follow up questionnaire clearly indicated from both
patients and nurses that the preferred route of administration is SC
injection. Saler et al., reports relative reductions in mean chair time,
reduced pharmacy preparation time and increased ability to improve
the number of other patients that can be treated increasing a facility’s
overall efficiency by administering Rituximab SC versus Rituximab IV.
This is supported by De Cock et al. time and motion study compiled
by 8 different countries highlighting the benefits of subcutaneous
administration of Rituximab.
requiring treatment for both acute and chronic Graft vs. Host (G vs. H)
disease. It has been demonstrated to be safe and efficacious offering
clinical benefits for refractory graft vs. host disease particularly but not
limited to the skin. Limited experience and data however, is available re:
a treatment protocol for children.
We now frequently treat children in our outpatient clinic with ECP,
many who travel from referral centres, which has necessitated the
need to address specific pediatric and resource implications. This
includes working together with the interdisciplinary team in the pre
procedure planning to identify potential issues both procedure and
patient specific. Issues related to patient selection, venous access, diet,
medication adjustment and maintenance of adequate blood counts
must be assessed and addressed. The role of nursing is additionally
important in both the pre and post treatment family teaching in order
to maintain patient safety. Ongoing liaison and coordination with the
multiple services involved and advocating for the patient and family
have been essential for successful implementation of the schedule of
treatments due to both the significant length and psychological impact
of treatment protocols.
Objectives include a brief overview of chronic G. vs. H. disease together
with mechanisms of action of ECP, discussion of patient selection, pre and
post procedure treatment complications and patient and family teaching
necessary for the safe implementation of a course of ECP therapy.
Conclusion
To date SC Rituximab is non-inferior and has a comparable safety
profile when compared to IV Rituximab. A SC injection of Rituximab
could have many benefits for Alberta cancer patients including reduced
wait times for patients and families, reduced health care provider time
related to administration and supplies, reduced drug preparation time
for pharmacists, and increased availability of space for other patients
needing cancer treatments overall improving efficiency in a Cancer
Center. These benefits are possible ensuring efficacy and optimal
treatment of the patient’s disease. Limitations: Currently no clinical
trials in Alberta related to the administration of Rituximab SC. Limited
Canadian studies.
8. EXTRACORPOREAL PHOTOPHERESIS IN A pediatric
AMBULATORY SETTING: ESTABLISHING A NURSING
PROTOCOL FOR CARE
Christine Armstrong, RN(EC), NP/Pediatrics 1,2, Anna Gascadi1, RN, BScN, Jane
Lowry1, RN
Blood and Marrow Transplant Program
. The Hospital for Sick Children, Toronto, Ontario, 2. Lawrence S. Bloomberg, Faculty of
Nursing, University of Toronto
1
Abstract Body
Often used in many adult treatment settings such as the protocol for
T-Cell Lymphoma, Extracorporeal photopheresis (ECP) has in recent
years become a viable treatment option for some pediatric patients
9. IDENTIFICATION AND MANAGEMENT OF
GLUCOCORTICOID-INDUCED HYPERGLYCEMIA ON A
BONE MARROW TRANSPLANT WARD: A QUALITY
IMPROVEMENT INITIATIVE
Aw A 1, Dutton H 2, Malcolm J 2, Keely E 2, Tay J 1,3
Division of Hematology, The Ottawa Hospital; 2Division of Endocrinology, The Ottawa
Hospital, and 3Ottawa Hospital Research Institute
1
Background
Hyperglycemia in malignant hematology inpatients has been associated
with increased adverse events. Glucocorticoids (GC) are commonly
used to treat hematologic malignancies, increasing the likelihood of
hyperglycemia. Studies identifying quality interventions in this setting
are lacking.
Methods
We performed a retrospective review of all admissions to the Bone Marrow
Transplant (BMT)/Malignant Hematology ward at The Ottawa Hospital
between September 1 to November 30, 2012 to document current
practices for identifying and managing GC-induced hyperglycemia.
Admissions were included if at least one dose of GC was given during
hospital stay. We assessed 1) glucose monitoring strategies, 2) glycemic
control quality and 3) hyperglycemia therapies during the first 7 days of
GC use, and up to 24 hours post discontinuation. Associations between
35
adverse events of infection, readmission, or Emergency Department visit
within 30 days of GC initiation were assessed using regression analyses.
Results
We identified 77 encounters: median age 57, commonest diagnosis
acute leukemia (31%), and stem cell transplant most frequent reason for
admission (19%). At least one glucose measurement was performed in
95% of cases. Scheduled qid point-of-care testing (POCT), correctional
scale insulin, and scheduled basal or prandial insulin were ordered in
19%, 14%, and 3% of admissions respectively. Average fasting glucose
was < 6.1 mmol/L in 38%, 6.1 - 10.0 mmol/L in 57%, 10.1 - 14.0
mmol/L in 3%, and > 14.0 mmol/L in 1.5%. In the 48 admissions with
at least one glucose measured in the non-fasting state, 10% had an
average non-fasting glucose greater than 10.0 mmol/L. There were 4%
and 10% of admissions with hypoglycemic (<4.0 mmol/L) and extreme
hyperglycemic (>14.0 mmol/L) events respectively. No associations
between fasting glucose and adverse events were identified.
– 10 days after the first thaw. Four of the pairs were subjected to a
subsequent final thaw 27 - 36 days following the initial thaw. Viability
studies were completed after each thaw and reported as the proportion
of viable cells that were initially cryopreserved.
Results
Four of the 5 pairs demonstrated a high degree of consistency with
respect to viability at first thaw (70 – 85%). There was a significant
discrepancy in one pair that had been cryopreserved for 16 years (75
and 40%). The mean viability after the initial thaw was 74%. The
recovery after re-freezing for 7 – 10 days declined to approximately
60% of the original cryopreserved cell number (Table 1). A further
reduction of viability to approximately 42 % was observed at the third
thaw. The viability was similar after re-freezing at - 86°C and -180°C.
Cell viability of control samples kept at room temperature or 4°C
dropped to less than 5% within 24 hrs.
Post Thaw Re-frozen Post Thaw Post Thaw
1 (Mean %)
at
2 (Mean %) 3 (Mean %)
Conclusion
GC-induced hyperglycemia is common in patients admitted to the BMT
ward. Only 19% of cases had scheduled qid POCT. The Canadian Diabetes
Associations recommends glycemic monitoring for at least 48 hours in
patients started on GC, identifying a practice gap. Our local audit provides
a foundation for future Quality Improvement interventions.
10. COUNT RECOVERY AND VIABILITY AFTER SERIAL
REFREEZING OF CRYOPRESERVED STEM CELL GRAFTS
Jamal N, Alvarez M, Lopez-Perez O, Bardia D, Yasay J, Messner HA
Princess Margaret Cancer Centre, University Health Network, Toronto
Rationale and Study Objective
The integrity of cryopreserved stem cell grafts may be compromised by
equipment failure resulting in unplanned thawing of products, breakage
of the container or other events that may delay the infusion of an already
thawed product. Viability of thawed products declines within 24 hrs. to
levels that do not facilitate engraftment. We investigated the question of
whether or not viability of a thawed stem cell product could be sustained
by rapid re-freezing.
-86°C
67 (60 – 75) 46 (41 – 50)
-180°C
57(20 – 75)
41 (5 – 58)
*The Mean and Median viability of 19 independent control samples at
thaw before infusion was 71.5 and 72 % respectively.
Conclusions
Previously cryopreserved stem cell products with prolonged storage intervals
of 9 to 16 years at -180°C can be serially re-frozen with a reasonable
recovery of viable cells. The yield is independent of the respective refreezing temperature of -86°C and -180°C, and is substantially higher
than that observed after storage at room temperature or at 4°C. Rapid
re-freezing of a compromised thawed stem cell product might represent
an effective strategy to salvage sufficient cells for successful engraftment.
At this time there are no clinical data available.
11. COLLECTION EFFICIENCY IN STEM CELL COLLECTIONS:
EXPLORING FACTORS AFFECTING COLLECTION EFFICIENCY
Cojocari E 1, Clarke S 1,2, Messner H 2
Methodology
Apheresis Unit, Princess Margaret Cancer Centre, University Health Network, Toronto;
Blood & Marrow Transplant Program, Princess Margaret Cancer Centre, University Health
Network, Toronto, Canada
1
The study was performed using a pair of products from 5 patients
cryopreserved in the vapor phase of liquid nitrogen for 16, 12, 10
and 9 (x2) years. The grafts were not further required for infusion into
the intended recipient and released with consent for the purpose of
this investigation. The products were thawed following standard
procedure and serially re-frozen. One of the pairs was cryopreserved in
a mechanical freezer at -86°C, the other at -180°C in the vapour phase
of liquid nitrogen. Viability was evaluated after each thaw by TrypanBlue staining. The thawing and re-freezing procedure was repeated 7
36
Cell
74 (40 – 85)
viability*
2
Background
In many stem cell collection centres, the decision-making process of
planning an apheresis stem cell collection involves first an estimation
of the CD34+ cell yield.
The ability to accurately predict as to the CD34+ cell yield using a formula
is important to ensure an optimal collection procedure. However, some
stem cell collections may unexpectedly result in poor CD34+ cell yields,
due to low collection efficiency (CE). The current methods to estimate
stem cell yield typically are inadequate in predicting when collection
efficiency will be less than optimal as they are based on pre-CD34+
cell counts, volume of processed blood and the donor’s weight. Current
formulas do not adjust for other factors which could influence collection
efficiency.
Methods
The goal of this study was twofold: 1) to identify the most probable
factors which may contribute to low stem cell collection efficiency
and 2) to develop a decision making algorithm in order to improve
predictions of CD34+ yield. To explore these issues, we undertook a
retrospective study of allogeneic and autologous stem cell collections
which were harvested with two types of apheresis systems at a large
apheresis unit at the University Health Network, Toronto, Canada. A
total of 110 consecutive apheresis procedures were performed on 78
donors/patients. We analyzed the interactions between CE and the
following variables: type of apheresis system utilized (Cobe Sprectra®
versus Spectra Optia®), donor type (autologous, allogeneic), diagnosis,
age, sex, weight, mobilization method (granulocyte-colony-stimulating
factor with or without chemotherapy), peripheral blood CD34+ cell
concentration, total processed blood volume, hematocrit, white blood
cell, platelets count, and mean inlet rate.
12. ENUMERATION OF CD34+ CELLS USING AN ACCURI
C6 CYTOMETER
Simard C1, Cloutier M1, and Néron S1
Research and development, Héma-Québec, Quebec City, QC.
1
CD34+ cell enumeration by flow cytometry: a comparison of two Health
Canada approved kits analyzed on an Accuri C6.
Background
Enumeration of CD34+ cells in umbilical cord blood, bone marrow or
peripheral blood is an important data for critical clinical choices in stem
cell transplantation therapy. Single platform cytometry assays have
become the primary option for stem cell enumeration. The purpose of
this study was to assess the feasibility of using commercial kits from BD
and Beckman Coulter on an Accuri C6 cytometer for the enumeration of
CD34+ cells in umbilical cord blood.
Methods
The Stem Cell Enumeration Kit from BD and the Stemkit from Beckman
Coulter were used to stain either a solution of blood doped with known
quantities of CD34+ cells or a commercial stabilized leucocytes solution
containing validated concentrations of CD34+ cells (Streck CD-Chex®
CD34). Stained samples were analyzed on an Accuri C6 cytometer
according to the ISHAGE protocole.
Results
Results
Our preliminary results demonstrate that CD34+ cell CE may considerably
vary from one stem cell collection to another when comparing the COBE
Spectra (Mean 46.8 %, SD 15.1) to the Spectra Optia® (Mean 52.4 %,
SD 13.7) apheresis systems.
The staining with both kits resulted in stable, sensitive, reproducible and
specific results when analyzed on the Accuri C6. The regression analysis
gave R-square values of 0.9997 and 0.9966 for the Beckman Coulter
and BD kits, respectively. Staining of the CD-Chex® CD34 resulted in
numbers of CD34+ cells inside the range given by the manufacturer.
Conclusion
In conclusion, both the BD and Beckman Coulter kits, coupled with the
cytometer Accuri C6, allow the quantification of CD34+ in a range of
concentrations corresponding to the three major sources of stem cells.
13. ANTIMICROBIAL ACTIVITY IN CORD BLOOD UNITS:
OCCURRENCE AND LEVELS OF ANTIBIOTICS
Marie-Pierre Cayer1, Mélissa Girard1, Diane Fournier2, Gilles Delage3,
Louis Thibault1
1
Héma-Québec, Research and Development, Quebec (QC), Canada, G1V 5C3; 2HémaQuébec, Public Cord Blood Bank, Montreal (QC), Canada, H4R 2W7, and 3Héma-Québec,
Medical Affairs, Montreal (QC), Canada, H4R 2W7
Conclusion
This presentation will describe our analysis and proposal of a decision
making algorithm which would assist apheresis clinicians to maximize
collection efficiency and thus improving the overall quality of stem cell
collections.
Purpose
Antibiotic prophylaxis treatment at delivery is highly recommended
for reducing the risk of infection for mothers positive for group B
streptococcus. It is therefore expected that some cord blood (CB)
37
products will contain residual antibiotics. This study aimed to determine
the incidence and level of β-lactam antibiotics in CB products.
Methods
The antimicrobial activity of 60 CB plasma by-products was evaluated
using disk diffusion assays on 10 bacteria species. Plasma samples
showing antimicrobial activity were either treated with β-lactamase
enzyme to inhibit β-lactam antibiotics or heated to 56°C for 30 minutes
to inhibit complement proteins. β-lactam antibiotic concentrations were
determined in these plasma samples and in 5 samples of final stem cell
concentrate by comparison with a standard curve obtained with known
concentrations of antibiotics.
Methodology
All adult centres performing autologous HSCT for hematologic
malignancies in Canada were electronically polled along with selected
major US centres. Descriptive statistics were performed using Microsoft
Excel.
Results
Results
Antimicrobial activity, mostly against Gram positive microorganisms,
was observed in 33% of CB units. The β-lactamase enzyme abolished
the antimicrobial activity in the majority of these CB products whereas
the inhibitory activity remained after heating at 56°C, indicating that
complement proteins are not involved. Up to 5 µg/mL of penicillin and 14 µg/
mL of ampicillin were measured in CB plasma and in stem cell concentrates.
Data was collected from 14 Canadian centres and 7 US centres. 7/21
(33%) do not routinely use G-CSF following autologous HSCT. Of the
Canadian centres routinely using G-CSF post-transplant: 3/9 start on
day +5 and 6/9 on day +7. Weight-based with a cap of 300/480mcg
was the most commonly reported dosing method. The decision to stop
G-CSF is based on neutrophil recovery in all centres.
Conclusion
Conclusions
About one third of CB products can contain significant amounts of
plasma with residual antibiotics which can affect the survival and
growth of bacterial contaminants when performing sterility testing and
potentially lead to false negative results. Additional work is required
to better understand whether residual antibiotics in cord blood affect
penicillin-allergic patients.
Despite evidence and guidelines that support the routine use of G-CSF
following autologous HSCT for hematologic malignancies there is
marked heterogeneity in practice. The most common dosing regimen
reported is to start d+7 with a capped weight-based dose and to stop
when the ANC is greater than 1.5. However, this protocol represents
only one-third of reporting Canadian centres. Future work needs to
be directed to determine if variation in practice results in clinically
meaningful outcomes.
14. OPTIMIZING THE USE OF G-CSF FOLLOWING
AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT
FOR HEMATOLOGIC MALIGNANCIES: AN ANALYSIS OF
CANADIAN PRACTICE
Hillis C1, Brown M2, Walker I1,2
Department of Medicine, McMaster University and 2The Juravinski Hospital and Cancer Centre
1
15. INFECTION PREVENTION AND CONTROL RELATED TO
RESPIRATORY VIRAL ILLNESS IN HEMATOPOIETIC STEM
CELL TRANSPLANT (HSCT) RECIPIENTS: THE OTTAWA
HOSPITAL EXPERIENCE FROM 2008-2012
Landry C1, Hamelin L1, Duke K2, Bruce N3; Doyle T3; Roth V3, Bredeson C1
Objective
The Ottawa Hospital Blood and Marrow Transplant Program; 2The Ottawa Hospital
Cancer Centre; 3The Ottawa Hospital Department of Infection Control.
1
To determine Canadian practice patterns for the use of granulocyte
colony stimulating factor (G-CSF) after autologous hematopoietic stem
cell transplant (HSCT) for hematologic malignancies in adults.
Rationale
There are guidelines and meta-analyses of randomized controlled trials
that support the use of G-CSF following autologous HSCT to reduce
both length of hospital stay and post-transplant morbidity. It is unclear,
however, what day following stem cell reinfusion (day 0) is optimal for
starting G-CSF to balance clinical benefit and minimize costs. Previous
studies have shown no difference in post-transplant stay and complications
38
for groups with early (day 0 or +1) vs delayed (day ≥ +5) administration
of G-CSF. At our centre alone delaying G-CSF administration by 2 days
(changing from d+5 to d+7) could potentially save $33,800-$54,081
annually. Prior to instituting a practice change, we sought to determine
if a standard regime for G-CSF following autologous HSCT exists across
Canada and major centres in the United States.
Introduction
Respiratory viral illnesses (RVI) can present a significant cause of
morbidity and mortality in the immunocompromised HSCT recipient.
The onset of RVI correlates with the prevalence of viruses circulating in
the community. In order to avoid an outbreak—defined as any hospitalacquired case of RVI—on the 24 bed Blood and Marrow Transplant
(BMT) unit of our adult transplant program, interventions (quality
initiatives) were required to ensure patient health and safety was not
compromised. An interdisciplinary committee was established to review
current practices and develop a standardized approach to managing
patients during peak season. Specifically, modifications have been
made to (1) patient environment; (2) staff and patient education; (3) the
program approach to staff vaccination; (4) existing processes to prevent
nosocomial outbreaks and reduce instances of microbial transmission.
Summary
In 2008 our program experienced an outbreak of parainfluenza-3.
Total instances of RVI in patients post-HSCT equaled 12/117 (10.2%),
with 1/3 of those requiring ICU admission linked to RVI and 3 deaths
attributed to RVI-related complications. Measures indicated in Table
1 were implemented between 2009 and 2012. Annual instances of
RVI in HSCT patients transplanted annually from 2009 to 2012 were
7/123 (5.69%), 2/107 (1.87%), 5/119 (4.20%), and 8/108 (7.41%)
respectively.
Table 1. Modifications implemented by program to reduce microbial
transmission and avoid escalation of nosocomial outbreaks.
Initiative
Patient
Environment
•
•
•
•
Education
•
•
Vaccination
•
•
•
Process
Improvement
•
•
•
•
BMT day program private rooms reserved
in low traffic area of wing
Transitioned to secured unit with visitor
screening
Medical day care unit (MDCU) moved offunit to limit traffic on unit
Outpatient waiting room modified with
glass barriers
Additional patient education provided,
including letters to patients/caregivers
Education module given to nurses
Mobile flu shot clinics; posters;
stations outside cafeterias; newsletter
communication
Weekend flu shot clinics for family/staff
All BMT caregiver/family members
encouraged strongly to get flu vaccine,
administered by BMT program when
required in outpatient clinics
Increased collaboration/communication
with hospital infection control on
emergent trends
Development of guidelines/action plan for
staging outbreak scenario
Febrile Respiratory Illness (FRI) screening
tool implementation
Fast turnaround pre-BMT nasopharyngeal
swab (NPS) screening, with BMT delay if
needed
Conclusion
Increasing constraints with bed availability and a growing number of
patients eligible for HSCT underscored the importance of developing a
strategy in order to avoid a closure of the BMT unit (crisis). No outbreaks
have been reported on our unit during the current 2014 flu season.
Continued vigilance and future monitoring of trends associated with
community respiratory outbreaks will complement our efforts to reduce
the burden of RVI transmission in order to lower the incidence of RVIassociated morbidity and mortality at our centre.
16. THE HEMA-QUEBEC PUBLIC CORD BLOOD BANK
(CBB): DISTRIBUTION AND CLINICAL OUTCOMES OF
TRANSPLANTED UNITS
Joron S, Fournier D, Pelletier G, Richard L, Chevrier MC, Champagne M
Héma-Quebec Public Cord Blood Bank, Montreal, Québec.
Introduction
Héma-Quebec’s CBB was established in 2004 to increase transplant
accessibility in both Canada and worldwide. The Héma-Quebec CBB
has both FACT-NETCORD and ASHI accreditation as well as NMDP
IND licensing. Our CBUs have been recently added to the BMDW
international database as of October 2012. Recently, the aim of our CBB
has been to increase ethnic diversity, as well as increasing the number
of CBUs with high TNC. Non-Inherited Maternal Antigen (NIMA) HLA
typing was also introduced march 2013.
Methods
Qualification is based on a questionnaire that identifies risk factors
for infectious and genetic transmissible diseases. Cell count criteria
range between ≥ 1,1 x 109 TNC (non-Caucasian) and ≥ 1,3 x 109 TNC
(Caucasian) based on ethnicity. CBUs are plasma and red cell reduced
(Optipress II) and cryopreserved in 10% DMSO with a target volume
of 25mL. HLA-A, B and C are typed at intermediate/high resolution,
DRB1 at high resolution. Clinical outcome information was volunteered
directly by transplant centers and via CIBMTR.
Results
As of January 1st, 2014, 51 units have been distributed for 47 patients (26
pediatrics and 21 adults). In 2013, our CBB has distributed 26 CBUs in 8
countries: 6 in Canada; 10 in the United-States; 9 in Europe and 1 in South
America. 21 out of the 51 units were used for single unit transplants and
22 for multiple CBU transplants (8 unknown). Post-processing median cell
dose of distributed units is 7,0 x107 TNC/kg (median of 9,8 x107 TNC/kg
for pediatric patients; median of 2,9 x107 TNC/kg for adult patients) and
median viable CD34+ count is 3,8 x105 CD34+/kg (median of 5,1 x105
CD34+/kg for pediatric patient; median of 2,0 x105 CD34+/kg for adult
patients). Out of the 51 distributed units, 7 were 6/6 HLA match, 23 were
5/6 match and 21 were 4/6 match.
39
For 20 of the 47 post-transplant patient outcome data received (15 pediatric;
5 adults), median hematopoietic recovery (ANC ≥0,5 x109/L, platelets ≥ 50
x109/L) was 18 and 39 days (2 patients never engrafted), respectively. Half of
the patients had no incidence of GVHD. Out of the 20 post-transplant data
received, 8 patients survived ≥1 year post transplant (4 recently transplanted).
12 out of the 20 patients are still alive (8 pediatric and 4 adult).
Conclusion
Units provided by Héma-Québec’s CBB resulted in favorable
hematopoietic recovery when compared to published data. Prospective
post-transplant outcome data collection for patients transplanted with
Héma-Quebec CBU is ongoing.
17. HUMAN ALBUMIN EYE DROPS IS SAFE AND
EFFECTIVE ALTERNATIVE FOR THE INDICATION OF
KERATOCONJUNCTIVITIS SICCA SECONDARY TO GVHD
POST ALLO-STEM CELL TRANSPLANTATION
Jack T. Seki1,6, Sarah Moldenhauer1,5, Naoko Sakurai1, Jessica Dam1,
Eshetu G. Atenafu1, Paul M. Yip2, Tony Mazzulli3,6, Tina Henderson4,
Jacob Pendergrast2, Christine Cserti2, Juan P. Velazquez1, Rand
Simpson1, Giorgio Felluga1, Hans Messner1, Jeffrey H. Lipton1
Princess Margaret Cancer Centre1, Toronto General Hospital2, Mount Sinai Hospital3,
The Hospital for Sick Children4, Drake University5, Iowa, Leslie Dan Faculty of Pharmacy,
University of Toronto6, Toronto, Ontario,
Background
Eye complication of Keratoconjunctivitis Sicca (KS) from graft-versushost disease (GVHD) post allogeneic stem cell transplantation (AT) is
common. Patient complaints are described as feeling of severe dry
eye, foreign object-like or grittiness, irritating, burning, itchiness,
blurry vision and pain. When examined, the eyes can be erythematous,
hyperpigmented, edematous with discharge and inflammation of the
cornea and conjunctiva. It can lead to severe damage and blindness if
not treated. Remedies have included topical corticosteroids, lubricating
eye drops, punctal plugs, immunomodulation, and autologous serum
eye drops. We sought to examine the efficacy and safety of pooled
Human albumin eye drops (HAE) as a viable therapeutic option.
Methods
We analyzed retrospectively 39 AT patients between Jan 2000 and July
2013, for clinical efficacy and safety using HAE for KS symptom relief
after other alternatives had failed.
The HAE were subjected to quality assurance testing on Day 1 for
sterility, oncotic pressure, albumin measurement, viscosity, pH and purity
by protein electrophoresis. A random 4% sampling rule applied for all
tests. These tests mimicked freeze (minus 20° C)-thaw cycle during
transportation of HAE from hospital to patients’ home during summer
months. Similar tests performed over a period of 16 hours mimicking
eye applications while awake. These tests were repeated on Day 30.
40
Results
General symptom relief occurred in 34 (87%) patients, including 6 patients
who required ongoing HAE treatment, compared to five (13%) patients
who failed to improve with HAE (p <0.0001). Initial symptoms and levels
of severity were compared to the post treatment symptom relief using the
CTCAE v4 grade scale. The proportion of post treatment symptom relief
by two grade levels from 3-1 (59%) is significantly higher than that of
one grade level from 3-2 (18%) and from 2-1 (23%) (p=0.0064). Time to
achieve symptom relief ranged from 2-28 weeks. Nineteen (48%) patients
had symptom relief between weeks 2-4 of start of treatment. Five (13%)
patients responded in 8 weeks. HAE was generally very well tolerated.
Thirty-five (90%) patients had no adverse reactions (ADR), while one each
had burning and stinging pain. No record of any documentation of ADR
in 2 patients. Prior and/or concurrent therapies included acetylcysteine,
topical lubricating eye drops and ointment, lower tear duct cauterization,
topical corticosteroids, topical antibiotics, cyclosporine eye drops, topical
non-steroid anti-inflammatory agents, and lacrimal punctual plugs.
Test #
Test
Day 1
Day 30
Hour 0
Hour 16 Hour 0
Hour 16
Negative
n/a
n/a
n/a
1
Sterility
2
Oncotic Pressure 15.6
(mmHg)
15.9
17.4
17.4
3
Albumin (g/L)
45
46
46
46
4
Viscosity
(Centipoise)
1.16
1.26
1.59
1.35
5
pH
6.77
6.74
6.79
6.77
6
Purity
96%
n/a
97%
n/a
Conclusion
Patients with post AT-related ocular complications were well managed
with HAE in conjunction with other remedies when they have failed.
HAE was well tolerated overall. Quality assurance tests showed that
HAE maintained chemical and physical stability over a period of 30 days.
18. EFFECTS OF IONIZING RADIATION ON MESENCHYMAL
STEM CELLS IN PATIENTS WITH AML: IMPLICATIONS FOR
TBI-BASED HEMATOPOIETIC CELL TRANSPLANTATION
STRATEGIES
Yevgeniya Le1,2,3, Richard B. Richardson1, Mitchell Sabloff2,3 and David
S. Allan2,3
1
Atomic Energy of Canada Ltd., 2Ottawa Hospital Research Institute, 3University of Ottawa.
Ottawa, ON, Canada.
Background
Conditioning regimens based on total body irradiation are being studied
in allogeneic hematopoietic cell transplantation (HCT) for high risk
acute myeloid leukemia (AML). Following transplant, the bone marrow
microenvironment remains predominantly patient-derived and host
mesenchymal stromal cells (MSCs) maintain the cellular components
that support hematopoietic niches. We hypothesize that persistent
abnormal MSC function after HCT contributes to a permissive bone
marrow environment and an elevated risk of relapsing disease. In this
study, we have compared MSC function from patients with AML and
healthy controls and tested the effects of high dose radiation.
Methods and Results
Normal and AML-derived MSCs were treated with TBI-like gamma
radiation (200 cGy x 6 fractions). Flow cytometric analysis revealed
typical surface marker expression profiles for MSCs derived from patients
with AML and from normal controls and no significant changes were
observed following radiation. However, MSCs from AML patients had
increased adipogenic and decreased osteogenic capacity in comparison
to normal controls and irradiation of healthy MSCs resulted in the same
abnormal differentiation profile as observed in AML-derived MSCs. AMLMSCs had decreased proliferation, as measured by BrdU incorporation
and CFU-F assay, and increased necrotic cell death. Radiation treatment
substantially decreased both normal and AML-MSC cell proliferation rates
and completely inhibited colony formation. Finally, immunocytochemistry
demonstrated substantial generation of H2A.X histone following
irradiation in both normal and AML-derived MSCs, suggesting extensive
DNA damage and induction of DNA repair mechanisms.
Conclusions
Taken together, MSCs from AML patients exhibited skewed
differentiation potential with increased adipogenesis and decreased
osteogenesis and had reduced proliferation capacity compared with
controls. Radiation treatment induced similar changes in normal MSCs.
The persistence of abnormal marrow-derived MSC function following
HCT may be exacerbated by TBI and measures to restore normal MSC
function may be required. Strategies that could restore normal MSC
function in conjunction with HCT appear worthy of further development
and testing.
19. MESENCHYMAL STROMAL CELL TREATMENT IN
XENOGENEIC CHRONIC GRAFT-VERSUS-HOST DISEASE
MOUSE MODEL
Hisaki Fujii1,2, ZhijuanLuo2, Hye Jin Kim2, Xinghua Wang3, Susan
Newbigging4, Armand Keating3, Maarten Egeler1,2
Div. of Hematology/Oncology1, Developmental Stem Cell Biology2, The Hospital for
Sick Children, Cell therapy program, Princess Margaret Hospital3, Toronto Centre for
Phenogenomics4, Toronto, Canada
transplantation-related mortality (TRM) in allo-HSCT survivors. Despite
a number of clinical observations showing potential of Mesenchymal
stromal cells (MSCs) in reducing acute GvHD, the mechanism of action of
MSCs especially for cGvHD remains elusive due to lack of in vivo model
to test huMSCs. A subtype of MSCs shows strong immune suppressive
function (called MSC2) after stimulation of TLR3 ligand or IFN-γ. We
hypothesize that MSC2 is able to inhibit cGvHD. Given the inconsistent
result of muMSCs treatment in murine (mu)GvHD models, and the
biological differences between mouse and huMSCs, there is a need for
establishing a pre-clinic humanized cGvHD model. Here, we established
a humanized cGvHD model with lung fibrosis mimicking human cGvHD 8
weeks after transplantation to test the effect of MSCs/MSC2.
Material and Method
NSG mice were treated with cyclophosphamide/TBI followed by
injection of 1x106 G-CSF mobilized human PBMCs or 1x105 CD34+
cells. Samples of skin, lung, liver, spleen were taken, and fixed in 10%
neutral-buffered formalin, embedded in paraffin, and stained with
H&E and Masson’s trichrome and were evaluated by a pathologist in a
blinded manner. Fibrosis was quantified on trichrome-stained sections
as a ratio of area of blue staining to area of total staining. huBM-MSCs
were stimulated with huIFN-γ or PolyIC in vitro and assessed for IDO
expression level in MSCs by real time PCR and flowcytometry. Mice will
receive either non-stimulated MSCs, IFN-γ or polyIC stimulated MSCs 4
and 6 weeks post HSCT via tail vein.
Results
Mice that received over 60mg/kg of cyclophosphamide lost weight and
died earlier than those receiving 20mg/kg or less. Subsequently we used
20mg/kg cyclophosphamide combined with 200cGy TBI as conditioning
for the study. Mice that received 1x106 huPBMCs did not show any
sign of acute illness, weight loss or diarrhea, however, exhibited the
pathological changes 8 weeks post-transplantation. There were
aggregates of inflammatory cells surrounding portal triads and blood
vessels in liver and a few areas of expansion of airways in the lung.
Masson’s trichrome revealed that mice with G-CSF mobilized huPBMCs
had significantly increased lung fibrosis compared to controls, which
is confirmed with the imaging quantitative analysis and the pathology
score. Immunohistochemistry (IHC) analysis showed abundant huCD4+T
and macrophage infiltration in the affected lung, which is likely to play
major roles in fibrosis formation in this mouse model. We found that
IDO mRNA expressions in huMSCs were continuously increased with
IFN-γ (500IU/ml) up to 24 hrs in dose dependent manner, but was
increased when incubated with polyIC (1mcg/ml) only for 4 hrs. IDO
protein expression was also confirmed by flowcytometry. MSCs/MSC2 in
vivo effect on this model is currently under investigation.
Conclusion
Background
Chronic Graft-versus-Host disease (cGvHD) is the major cause of late
Here we presented the first humanized cGvHD with lung fibrosis in
which we will be able to study the effect of pathophysiology of IDO
41
inducible Mesenchymal Stromal Cells. This approach may be able to
lead to better treatment in patients with cGvHD.
20. MAJOR ABO INCOMPATIBLE BONE MARROW
TRANSPLANTATION IN CHILDREN: DETERMINING WHAT
RESIDUAL VOLUME OF DONOR RED CELLS CAN SAFELY BE
INFUSED FOLLOWING RED CELL DEPLETION
Katharine Patrick 1, Wendy Lau 2, Elizabeth McDougall 2, John Doyle 3,
Muhammad Ali 1, Adam Gassas 1, Jane Lowry 1, Maarten Egeler 1, Tal
Schechter 1
Division of Hematology & Oncology, The Hospital for Sick Children, Toronto; 2Department
of pediatric laboratory medicine, The Hospital for Sick Children, Toronto; 3Section of
Pediatric Hematology/Oncology, Department of Pediatrics and Child Health, University of
Manitoba
1
Background
Red cell depletion of major ABO incompatible bone marrow (BM)
reduces the risk of acute haemolysis during haematopoietic stem cell
transplantation (HSCT). However, residual red cells remain.
In children, this volume can be significant relative to their body weight.
We sought to determine the volume of incompatible red cells (iRBCs)
from a major ABO mismatched donor that can safely be given to
children. This will answer a highly relevant clinical question, for which
no clear evidence based recommendation could previously be made.
Conclusion
We describe a large cohort of children who received HSCT from major ABO
incompatible donors and demonstrate that with careful hydration, close
attention to urine output, and monitoring of biochemical markers of renal
function and haemolysis, at least 3ml/kg of iRBCs can safely be given to
children. It should be expected that a degree of haemolysis will occur and
this should be monitored for. We recommend that if more than 3ml/kg of
iRBCs has to be given, BM is divided into aliquots and given at 4 to 8 hour
intervals to allow monitoring of renal function between each infusion.
21. ANTIBIOTIC PROPHYLAXIS THERAPY FOR PATIENTS
UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANT :
A TALE OF 2 CENTERS
Tal Schechter 1, Adam Gassas 1, Joshua Klein 1, John Doyle 2, Amanda
Berger 3, Muhammad Ali 1, Pengcheng Lu 3, Jennifer Domm 3, Maarten
Egeler 1, Sarah Alexander 1 , Haydar Frangoul 3
Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto,
Toronto, Ontario, Canada; 2Cancer Care Manitoba, 3Vanderbilt University, Nashville, TN,
1
Methods
All patients undergoing HSCT using fresh BM from a donor with a major
ABO blood group mismatch between January 2000 and August 2013 at
SickKids, were identified. A retrospective chart review was conducted.
Results
78 patients with a median age of 9.2 years (range 0.16 to 18
years) were identified. BM was red cell depleted using pentaspan
sedimentation in 74 of the cases. Antihistamines, acetaminophen and
hyperhydration (125ml/m2/hr) for 2 hours before BM infusion and at
least 4 hours after were given to all patients. The duration of the BM
infusion varied, depending on the volume of BM, the weight of the
child and the volume of iRBCs. The median duration was 4.5 hours
(0.3ml of iRBCs/kg/hr). The median volume of iRBCs transfused to
patients was 1.6ml/kg (range 0.1-10.6ml/kg). Patients were observed
for clinical and biochemical signs of haemolysis including hypotension,
haemoglobinuria, significant increases in creatinine (> 50% increase
from baseline) and significant increases in unconjugated bilirubin. 43
patients had no signs of haemolysis. 24 patients had a significant rise
in unconjugated bilirubin. 2 patients had a significant rise in creatinine
but neither required dialysis. 2 patients became hypotensive, one
required a single fluid bolus and one required a brief period of inotropic
support which was felt most likely to be related to infection due to the
absence of other signs of haemolysis. The only serious reaction occurred
42
in a patient who received 3.9ml/kg of iRBCs. The BM was given at a
rate of 135ml/hr (1.75ml of iRBCs/kg/hr). He developed hypoxia, an
unconjugated bilirubin 4 times the ULN and a doubling in creatinine.
Symptoms improved with prolonged hyperhydration, oxygen and
steroids. With a median follow up of 8.5 years, 51 patients were still
alive. Of the 27 deaths, 18 were due to non-relapse mortality, although
none were attributable to the infusion of ABO incompatible BM.
Background
Bacterial infections are a leading cause of morbidity and treatmentrelated mortality in children following hematopoietic stem cell transplant
(HSCT). Meta-analysis of studies of bacterial prophylaxis in adult
oncology patients with neutropenia showed a significantly decreased
risk of death associated with prophylaxis regimens. However, the use
of prophylaxis vs. empiric treatment is controversial in the setting of
HSCT and data in children is limited. The concerns for using prophylaxis
therapy are development of antibiotic resistance and increased drugrelated toxicity. An empiric approach to antibiotic therapy prompts the
concern that therapy is delayed until an infection has already occurred.
Our study aimed to compare the bacteremia rates in two pediatric
centers that use contrasting approaches; empiric vs. prophylaxis.
Methods
We compared the incidence of bacterial infections in pediatric HSCT
patients in two units; The Hospital for Sick Children (SickKids) where
an empiric antibiotic strategy is utilized and Vanderbilt University
Medical Center, where prophylaxis antibiotic (Cefipime) is given.
Baseline characteristics were compared between the 2 groups with 2
sample tests, where categorical variables and continuous variables were
evaluated using double-sided Fisher exact tests respectively.
Results
224 pediatric patients from SickKids and 294 pediatric patients from
Vanderbilt who underwent autologous and allogeneic HSCTs between
2005-2010 were evaluated. Total bacteremia rate (Gram positive
and Gram negative) was significantly higher at SickKids (66/224) vs.
Vanderbilt (49/294), p<0.001 (double sided Fisher exact test). At
SickKids, 19% presented with Gram positive infection as their first
infection (mean 8.9 d after transplant ) and 11% with gram negative
infection ( mean 4.0 d after transplant), whereas at Vanderbilt 14%
presented with gram positive infection (mean 9.5 d after transplant)
and 2% with gram negative infection ( mean 5.2 d after transplant).
No treatment-related mortality in the first 100 days was attributed to
bacterial infections in either center. SickKids had significantly more
gram negative bacteremia than Vanderbilt (p=<0.001). There was
also a trend toward lower incidence of gram positive bacteremia at
Vanderbilt (p=0.052).
Conclusion
The use of antibiotic prophylaxis in pediatric HSCT decreased the
incidence of bacteremia during transplant. The use of Cefipime as
a prophylaxis agent significantly decreased the incidence of gram
negative bacteremia with a trend toward reduction of gram positive
bacteremia. The use of antibacterial prophylaxis in pediatric patients
undergoing HSCT should be considered, and prospective studies are
needed to confirm our results.
22. CD8+ T LYMPHOCYTES FROM PEDIATRIC RECIPIENTS
OF BONE MARROW OR UMBILICAL CORD BLOOD
TRANSPLANTATION EXPRESS DIVERSE ASSORTMENTS OF
INHIBITORY RECEPTORS AT THEIR SURFACE IN THE EARLY
POST-TRANSPLANT PERIOD
Insaf Salem Fourati1,2, Catherine Gravel1,2, Martine Caty1, Samira
Mezziani4,5, Armelle Le Campion1, Michel Duval3,4,5, Hugo
Soudeyns1,2,3,5.
1
Centre de recherche du CHU Sainte-Justine; 2Department of Microbiology, Infectiology
& Immunology, Faculty of Medicine, Université de Montréal; 3Department of Pediatrics,
Faculty of Medicine, Université de Montréal; 4Hemato-oncology Service, CHU Sainte-Justine;
5
Groupe de recherche en transplantation et immunologie du sang de cordon (GRETISC),
Centre de cancérologie Charles-Bruneau, Montreal, Quebec, Canada.
Background
Umbilical cord blood transplantation (UCBT) is commonly used to treat
a variety of hematologic or neoplastic disorders in children. Compared
to bone marrow transplantation (BMT), UCBT is associated with slow
engraftment and a higher incidence of graft failure and opportunistic
infections. During chronic viral infection and cancer, CD8+ T cells
undergo functional and phenotypic changes that characterize a unique
state of differentiation termed « clonal exhaustion ». Our team previously
showed that CD8+ T cells expressed the PD-1 exhaustion marker during
the early phases of immune reconstitution in pediatric UCBT recipients,
and that higher frequencies of PD-1+ T cells were associated with
leukemic relapse. The aim of this study was to identify combinations
of exhaustion biomarkers that are expressed by CD8+ T cells and that
could predispose patients to develop complications following UCBT or
BMT.
Methods
Pediatric patients who underwent UCBT (n=16) or BMT (n=9) for the
treatment of leukemia or other hematologic disorders were enrolled at
CHU Sainte-Justine. Samples were obtained from graft inoculums and
from transplanted subjects during 24 months of follow-up. Expression
of inhibitory receptors associated with CD8+ T cell exhaustion, including
PD-1, CTLA-4, CD244, TIM-3, BTLA and LAG-3, was measured ex vivo
using multi-parameter flow cytometry.
Results
Results showed that all inhibitory receptors examined were expressed at
very low levels in UCB graft inoculums. However, a transient increase in the
frequency of CD8+ T cells that expressed either PD-1, CD244, BTLA, or LAG3, or co-expressing PD-1 and CD244 or PD-1 and BTLA was observed during
the first 100 days following UCBT. With the exception of PD-1, this transient
increase was not readily observed after BMT. In addition, frequencies
of CD8+ T cells that expressed either PD-1 or CD244, or co-expressing
PD-1 and CD244, PD-1 and BTLA, or PD-1 and LAG-3 were inversely
correlated with absolute CD8+ T cell counts. These results are suggestive
of a relationship between clonal exhaustion and delayed reconstitution of
the CD8+ T cell subset. Finally, CFSE dilution assays revealed that CD8+ T
cells that expressed at least one exhaustion marker did not proliferate as
extensively as control cells following in vitro stimulation.
Conclusion
These results indicate that expression of exhaustion markers by CD8+ T
cells in UCBT and BMT recipients during the early post-transplant period
may lead to functional impairment of these cells. This impairment could
potentially be relieved by the use of inhibitory receptor blockade.
23. PATHOGEN-SPECIFIC T-CELL LINE GENERATION FOR
THE TREATMENT OF VIRUS-RELATED COMPLICATIONS
AFTER TRANSPLANTATION
Orio J1, Carli C1,Taillefer J1, Richaud M1, Giroux M1, Janelle V1, Delisle JS 1,2
Centre de recherche de l’hôpital Maisonneuve-Rosemont (CR-HMR), 2 Hematologyoncology division, Department of medicine Hôpital Maisonneuve-Rosemont, University of
Montréal
1
Background
Opportunistic viral infections/reactivations post-transplant are
associated with significant morbidity and mortality. While some viral
complications can be prevented or treated with anti-viral medications
43
(or anti-CD20 in the case of EBV-driven lymphoproliferation), others rely
exclusively on adequate and timely immune reconstitution. Adoptive
immunotherapy using ex-vivo expanded pathogen-specific T-cell lines
has the unique potential to effectively treat opportunistic infections
and restore anti-viral immunity. We sought to develop clinical-grade
compliant T-cell cultures systems that would permit the rapid generation
of anti-viral T-cell lines from both memory and naïve repertoires.
Methods
We adapted the system developed at the Baylor College of Medicine to
differentiate and expand pathogen-specific T-cell lines from seropositive
healthy donors. Briefly, peripheral blood mononuclear cells are pulsed
with overlapping peptide libraries covering the entire sequence of
antigenic proteins and cultured in gas-permeable rapid expansion
cultureware (G-REX) along with IL-7 and IL-4. For seronegative donor,
we further adapted our systems by testing various combinations of
cytokines and using professional antigen-presenting cells (pAPC).
Results
Using EBNA1 and LMP2 peptide libraries to generate anti-EBV cell lines,
we observed a 10-20 fold expansion of T cells after 12 to 15 days in
culture. On average the cultures generated around 1.5-1.8x108 T cells.
Considering that several trials used a cell dose in the range of 107 to
2x107/m2 to treat active viral infections, a number of cell doses can
be prepared from a single culture. The generated T-cell lines showed a
slight CD8 predominance. Both CD4 and CD8 cells acquired a central
(CD45RO+/CD62L+) or effector (CD45RO+/CD62L-) memory phenotype.
The cell lines displayed antigen-specific interferon-gamma release and
cytotoxicity. No cytotoxicity towards allogeneic targets was detected.
T-cell lines with specificities directed against EBV, CMV, Adenovirus
and BKV were also generated. Our preliminary results using CMV
seronegative donors suggest that the use of pAPC is required to create a
CMV-specific T-cell line in this setting. We are currently investigating the
role of various cytokines to optimize T-cell differentiation and expansion
in this population.
24. IMPAIRED INTERFERON-ALPHA PRODUCTION BY
PLASMACYTOID DENDRITIC CELLS AFTER CORD BLOOD
TRANSPLANTATION: IMPLICATION FOR POST-TRANSPLANT
TLR-LIGAND BASED IMMUNOTHERAPY
Emily Charrier1, 2, Paulo Cordeiro 1, Rose-Marie Brito1, Michael
Harnois1,3, Samira Mezziani1, Sabine Herblot1, Françoise Le Deist1,3,4,
Michel Duval1-4
1
Groupe de Recherche En Transplantation et Immunologie du Sang de Cordon (GRETISC),
Centre de Cancérologie Charles Bruneau, Centre de recherche du CHU Sainte-Justine. 3175
chemin de la Côte Sainte-Catherine, H3T 1C5 Montréal, Québec, CANADA; 2Département
de Sciences Biomédicales, Université de Montréal, 3Département de Microbiologie et
d’Immunologie, Université de Montréal, 4Département de Pédiatrie, Université de Montréal.
Abstract Body
Post-transplant immunotherapy is a promising therapeutic avenue to
stimulate the graft-versus-leukemia (GvL) effect following allogeneic
hematopoietic stem cell transplantation (HSCT) and, in particular, cord
blood transplantation (CBT). Plasmacytoid dendritic cells (pDCs) are
attractive targets for post-transplant immunotherapy since they initiate
both innate and adaptive immune responses. Toll like receptor (TLR)
agonists are currently studied for pDC stimulation in various clinical
settings. Their efficacy depends on the number and functionality of
pDCs, which are unknown after CBT. We performed a longitudinal
study of pDC reconstitution in bone marrow transplanted (BMT) and
CBT patients. pDC blood counts were higher in CBT patients than in
healthy volunteers from 2 to 9 months post-transplant whereas pDC
blood counts were lower in BMT patients. We showed accordingly
that CB progenitors gave rise in vitro to 500-fold more pDCs than BM
counterparts. Upon stimulation with TLR agonist, pDCs from both CB
and BM recipients up-regulate T-cell costimulatory molecules, while
interferon-α (IFN-α) production was impaired for 9 months post-CB
transplantation. TLR agonist treatment is thus not expected to induce
IFN-α production by pDCs after CBT, limiting its immunotherapeutic
potential. Fortunately, in vitro production of large amounts of functional
pDCs from CB progenitors paves the way for post-transplant adoptive
transfer of pDCs.
Conclusion
Viral complications post-transplantation are a significant cause of
morbidity and mortality, especially in patients receiving their graft
from an alternate donor source. Attempting to treat these infections
by restoring anti-viral immunity is possible through adoptive
immunotherapy with donor or third party-derived T-cell lines. We have
adapted, designed and validated culture systems that can readily be
made clinical-grade compliant. Virus-specific adoptive immunotherapy
trials are in preparation at our institution.
25. CANADIAN PILOT CLINICAL TRIAL: LENTIVIRUSMEDIATED GENE THERAPY FOR ADULT FABRY DISEASE
Foley R, Khan A, Klassen J, Au BC, Tailor C, Rothe M, Bischof D, Sirrs
S, Auray-Blais C, Rupar T, Prokopishyn N, O’Hoski P, Huang J, Paul G,
Benabid R, Viswanathan S, Morel C, Raiman J, Schambach A, West M,
Keating A, Cornetta K and Medin JA.
Members of the CIHR-funded FACTs Study Team
Background
Fabry disease is the result of deficiency of alpha-galactosidase A
(alpha-gal A). Enzyme replacement therapy has limited clinical utility
and is costly. Advances in lentiviral-based gene transfer have revitalized
44
corrective stem cell therapy particularly in Lysosomal Storage Disorders
(LSD) where metabolic co-operativity effects can correct primary cells
and also get secreted and taken up into naive secondary populations.
test each year following donation. Approximately 75% of PBSC donors
have submitted results at least once, and the cumulative year to year
response rate is 47.9%.
Study
Methods
Our team has developed a “first in human” clinical trial in adult
Fabry patients. The platform is based on both laboratory and clinical
experience in autologous stem cell transplant and includes efforts of
the CBMTG. Our strategy is to employ “high-dose” (>10.0 x 106 /kg rec.
wt.) autologous CD34+ selected transduced cells infused into patients
following a single dose of melphalan (100mg/m2). Mobilization with
growth factors alone includes Filgrastim (10ug/kg) and Plerixafor
(240ug/kg) with large volume apheresis (25L) on days 5 and 6.
Annual means were calculated for each blood parameter and compared
between 30 randomly selected donors with all blood parameters in-range
prior to G-CSF administration (referred to as group A) and 31 randomly
selected donors with at least one out-of-range blood parameter prior to
G-CSF administration (referred to as group B). Donors’ pre- and post-GCSF administration blood parameters were also compared. Mixed model
analysis was performed to determine if the differences between groups
A and B, and if donors’ pre-versus post-G-CSF administration results
were statistically-significant.
Results
CD34+ cells have been enriched from apheresis products collected from
clinically stable volunteer adult male Fabry patient donors mobilized
with G-CSF alone. CD34+ cell yields to date have been in a range similar
to what is seen for normal SCT donors. GLP LV/FAB virus produced by
the Indiana University Vector Production Facility (IUVPF) at an MOI
of 10 has consistently led to >70% of input CD34+ cells positive for
transgene expression. Additional studies have measured specific gene
transfer frequency in progenitor colonies and viral integration events.
An in vitro assay has failed to show any evidence of immortalization of
murine hematopoietic stem cells and negligible cytotoxicity following
transduction with LV/FAB compared to controls. LV/FAB transduced
human Fabry CD34+ cells have been xeno-transplanted into a pure
NOD/SCID/Fabry mouse line with enzyme activity and substrate levels
(Gb3 and isoforms along with lyso-Gb3 and analogues) measured in
tissues from transplanted recipient animals. Effectiveness of the safety
cell-fate element have also been confirmed. We are currently at the
stage of completing a full ‘clinical dry run’ using clinical-grade virus
under GMP conditions.
Conclusion
These results will support the CTA and hopefully lead to timely initiation
of a clinical trial directed towards gene-based enzyme replacement for
adult patients with Fabry disease.
26. EFFECT OF G-CSF STIMULATION ON DONOR
BLOOD PARAMETERS FOLLOWING PBSC DONATION: A
ONEMATCH PILOT STUDY
Results
Statistically-significant differences in white blood cell (WBC) count,
hemoglobin, hematocrit, mean platelet volume (MCV), mean corpuscular
volume (MCH), and absolute neutrophils, monocytes, eosinophils, and
basophils between group A and group B and in donors’ pre- and postG-CSF blood work results, were not observed. Between groups A and
B, differences in mean red blood cell (RBC) count (p=0.0423) and
absolute lymphocytes (Lymph)(p=0.0493) were statistically-significant.
Within both groups of donors, mean platelets (PLT) were lower at 1 year
(p<0.01) and 3 years (p<0.05) post-donation, and mean corpuscular
hemoglobin concentration (MCHC) was also lower post donation
(p<0.01). Mean platelet volume (MPV) levels were higher post-donation
at years 1 and 2 (p<0.001). The mean results for select blood parameters
are presented below, where * denotes a statistically-significant result
(p<0.01) between the pre-G-CSF and post-G-CSF result:
Mean
x10 9/L
RBC
MCHC
WBC
LYMPH
Volesky K, Yi Q-L, Goldman M, Haun S, Stewart V, & Dufresne A
Background
PLT
To assess the possible long-term effects of granulocyte colonystimulating factor (G-CSF), OneMatch peripheral blood stem cell (PBSC)
donors provided a complete blood count (CBC) with differential blood
MPV
Group
Pre
G-CSF
n=61
Year 1
n=45
Year 2
n=44
Year 3
n=24
Year 4
n=22
A
4.86
4.86
4.79
4.69
4.68
B
4.57
4.68
4.75
4.66
4.77
A
344.59
338.74*
338.73*
336.21*
335.10*
B
345.55
342.26*
337.45*
336.08*
336.56*
A
6.87
6.64
6.58
7.03
7.13
B
6.67
6.40
6.17
6.63
6.16
A
2.14
1.96
2.21
2.13
1.89
B
1.72
1.42
1.83
2.05
1.84
A
253.03
232.43*
239.50*
250.64
243.42*
B
258.17
246.88*
241.02*
250.40
264.76*
A
9.13
10.82*
10.68*
9.77
10.19
B
9.05
10.80*
10.71*
10.77
9.19
45
Conclusion
Data from 61 OneMatch PBSC donors demonstrated differences in
MCHC, PLT, and MPV results pre- and post-G-CSF administration. In this
pilot study, no differences were observed in donors’ pre-versus postdonation WBC count with differential parameters. A forthcoming study
will examine all follow-up blood work results submitted to OneMatch to
validate these findings and to provide more long-term data.
27. DEVELOPING EDUCATIONAL RESOURCES TO ADVANCE
ETHICAL UMBILICAL CORD BLOOD RESEARCH: A
CANADIAN PERSPECTIVE
Beak C1, Allan DS2, Chargé SBP3, Isasi R1, Knoppers BM1. 1Centre of
Genomics and Policy, McGill University, Montreal, QC; 2Ottawa Health
Research Institute, Ottawa, ON; 3Centre for Innovation, Canadian
Blood Services, Ottawa, ON.
Abstract Body
As the therapeutic use of cord blood stem cells in transplantation
continues to grow, so too does the use of cord blood in research.
From studies to improve cord blood collection, manufacturing and
storing processes; to studies of the utility of cord blood to treat various
hematopoietic and non-hematopoietic disorders; to the use of cord blood
cells to derive pluripotent stem cells - cord blood research is making
important contributions to the scientific and clinical advancement of the
stem cell field. Obtaining an ample supply of such samples has been a
challenge for the research community. In 2013 Canadian Blood Services
(CBS) launched the National Public Cord Blood Bank (NPCBB) which
collects, tests and stores cord blood units for use in transplantation. As
part of their services, CBS is developing a system by which units that
are not suitable for storage and transplantation are available to the
scientific community for biomedical research purposes. To contribute to
capacity building of Research Ethics Boards (REBs), who will be tasked
with ensuring this research protects donors, we developed educational
resources designed to assist REBs in the evaluation of research protocols
which utilize cord blood samples. The “REB Primer on Research and
Cord Blood Donation” (the Primer), outlines key ethical and legal
considerations and identifies Canadian normative documents that are
relevant to the use of cord blood in research. It also introduces CBS
Cord Blood for research Program and describes the systems CBS is
implementing to address governance issues. The Primer is intended to
assist REBs in evaluating the ethical acceptability of research protocols,
facilitate harmonized decision making by providing a common reference,
and highlight the role of REBs in governance frameworks. However, it
was written to be accessible to the general public and may serve a
broader purpose to increase public awareness of cord blood banking
and the policies and procedures public systems have put in place to
protect donors.
46
28. POLYCLONAL HUMAN INTRAVENOUS IMMUNE
GLOBULIN (IGIV) WITH HIGH-LEVELS OF RSV
NEUTRALIZING ANTIBODIES: A SUMMARY OF ANIMAL
AND HUMAN STUDIES
Ann R. Falsey, Edward E. Walsh, University Of Rochester School Of Medicine,
James J Mond ADMA Biologics, Ramsey NJ
Rochester N.Y. and
Abstract Body
Respiratory syncytial virus (RSV) is a common cause of respiratory
infections in the bone marrow transplant population. Effective anti- RSV
agents are not available and current treatment options are limited. To
determine whether high titer neutralizing antibody to RSV might be of
benefit in this patient population we prepared a plasma derived, human
polyclonal immune globulin using plasma obtained from donors tested
for the presence of high levels of neutralizing titers to RSV. We studied
its ability to prevent infection in the cotton rat RSV model. Animals were
injected with the investigational product, RI-002, 10% IVIG, (“ADMA
IVIG”), and one day later were infected intranasally with RSV/A/Long
105 PFU/ animal and four days after infection with RSV. Plaques were
counted and viral titers were expressed as PFU per gram of tissue. The
control group had mean titers of ~4.7 Log10 PFU/g of tissue in the
lungs and the experimental groups given ADMA IVIG had undetectable
RSV viral titers in the lungs of all animals. This product was also used
in a compassionate use study in patients who were immunosuppressed
and had evidence of lower respiratory tract infection. Many had been
ill with RSV for days or weeks and had a high probability of mortality.
15 compassionate use patients aged 3 months to 71 years were treated
with ADMA IVIG at a dose of 1500mg/kg followed by 750mg/kg on day
3.The majority of these seriously ill patients had favorable outcomes
and there were no reports of serious adverse events attributable to the
study drug. Early administration of ADMA IVIG was associated with
a significantly higher survival rate compared to those who received
late treatment. These data support the further development of ADMA
IVIG for the prevention and treatment of RSV disease in the immune
suppressed population.
29. AN ASSESSMENT OF THE OUTCOMES OF SECOND
DONATION REQUESTS THROUGH THE CANADIAN
ONEMATCH UNRELATED REGISTRY
Arseneau I1, Couban S2, Ross M3, Thompson K4, Green M3, Amer B3,
Theriault C4, Goldman M3, and Shivakumar S2.
1
Faculty of Medicine, Dalhousie University; 2Department of Medicine, Division of
Hematology, Dalhousie University; 3Canadian Blood Services; 4Research Methods Unit,
Department of Medicine, Dalhousie University
Abstract Body
Few studies have examined second unrelated alloHSCT or DLI in a
consecutive series of patients and none involved the Canadian registry.
We examined Canadian patients who received a second unrelated
alloHSCT or DLI through OneMatch between January 2002 and
December 2011. Disease type, status at first transplant, transplant
date, indication and date of second transplant or DLI, graft types
(bone marrow, G-CSF stimulated peripheral blood or unstimulated DLI),
conditioning. Survival, disease status, and engraftment at last follow-up
and donor and recipient age and weight were collected.
128 consecutive Canadian patients received a second alloHSCT or DLI.
Median recipient age was 37 (2-68). There were 73 males, 36 females,
and 19 patients whose sex was unknown. The most common indication
for second transplant or DLI was disease relapse (n=68, 53%), followed
by graft failure (n=37, 29%). The most common indication for the first
transplant was AML (n=37, 29%), followed by lymphoproliferative
disorders (n=29, 23%). Most second transplants used unstimulated
peripheral blood (65, 51%), and 101 of 128 (79%) used the same donor.
Median survival was 1.03 years (95% CI = 0.87-1.69). Median time
between transplants was 10.6 months (0.6-105.7). Patients whose time
between transplants was above the median were more likely to survive,
(p=0.029) and had higher survival in the first year post-transplant. No
other factors significantly affected survival.
This study is the first to examine a consecutive series of unselected
patients receiving a second donation from an unrelated donor using the
Canadian registry. Survival is comparable to studies from the American
(Schriber et al., 2010) and German (Platzbecker et al., 2008) registries.
This study shows that outcomes do not differ significantly based on
disease, age, gender, conditioning and graft type. Further studies to
identify factors that better predict outcomes when utilizing this scarce
resource are needed.
presence of alemtuzumab was not previously reported.
Outcomes of unrelated-donor HCT (n=192) performed for myeloid
malignancies at our institution during 2006-2013 were analyzed.
Patients had T-cell depletion with alemtuzumab (n=111), or TRHCT (n=81). Recipients were CMV seropositive in 57%, and 59% of
alemtuzumab group and TR-HCT respectively.
In CMV seronegative patients no difference was observed in cumulative
incidence of relapse (CIR), non-relapse mortality (NRM), relapse free
survival (RFS) or overall survival (OS) between alemtuzumab and TRHCT. However, in CMV seropositive recipients alemtuzumab was
associated with higher CIR@5years; 28% vs. 2% (p<0.001), a trend
towards inferior RFS@5years; 24% vs. 49% (p=0.05), and a trend
towards inferior OS@5years; 22% vs. 49% (p=0.06). There was no
difference in NRM.
In CMV seropositive recipients alemtuzumab was associated with
lower incidence of grade 2-4 acute GVHD at 6 months; 46% vs. 69%
(p=0.04), and lower cumulative incidence of chronic GVHD at 3 years;
50% vs. 67% (P= 0.04). These effects were not observed in seronegative
patients.
In summary, the protective effect of CMV seropositivity on relapse was
not observed in alemtuzumab recipients; additionally, the negative effect
of alemtuzumab on relapse appears to have augmented in the presence
of CMV seropositivity. This needs to be confirmed in a larger population,
and further exploration of this may leads to better understanding of
(anti-leukemia) tumor immunity and immune reconstitution after HCT.
30. INTERACTIONS BETWEEN ALEMTUZUMAB AND
CYTOMEGALOVIRUS SEROSTATUS OF RECIPIENT IN
UNRELATED DONOR TRANSPLANT FOR MYELOID
MALIGNANCIES
Mohamed Shanavas, MD1, Naheed Alam MD1, Vikas Gupta MD1, John
Kuruvilla MD1, Jeffrey H. Lipton MD, PhD1, Hans A. Messner, MD, PhD1,
Mathew Seftel MD, MPH1, Jieun Uhm MD1, and Dennis (Dong Hwan)
Kim MD, PhD1
1
Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center,
University of Toronto, Canada
Abstract Body
Several studies have suggested a protective effect of cytomegalovirus
(CMV) serostatus on relapse risk after hematopoietic cell transplantation
(HCT). Generally these reports were in T-cell-replete HCT (TR-HCT), and
it is not clear whether such an effect is present in T-cell depleted HCT.
Alemtuzumab is a T-cell depleting agent with beneficial effect on graft
versus host disease (GVHD), but results in increased risk of relapse and
infections including CMV. The overall effect of CMV serostatus in the
47
conditioning (high dose chemotherapy with or without total body
irradiation -TBI) and stem cell transplantation. This study will help to
improve the understanding of how oral complications are related to
other side effects and to determine whether objective and subjective
oral complications related to treatment can predict negative clinical and
economic outcomes and reduced quality of life (QoL).
Materials and Methods
All adult patients who received a conditioning regimen followed by
stem cell transplantation (autologous or allogeneic) were eligible for
recruitment to the study. A standardised questionnaire was developed,
pilot tested and used to collect the clinical data prior to admission,
upon admission and following transplantation. This study is currently
in progress. A preliminary data analysis, prior to and upon admission
and 3 months follow up, was done with emphasis on transplantationrelated oral mucositis. Fisher’s exact test and Correlation test were used
to analyze data.
Results
Overall, 46 patients from only Vancouver site were evaluated in this
interim analysis. The mean age was 58.3 years. Twenty two patients
underwent autologous stem cell transplant and twenty four patients
underwent allogeneic stem cell transplant. In total, 30% of patients
presented with oral mucositis. The most common sites of involvement
were the buccal mucosa and ventrolateral tongue. There was a strong
relation between Mucositis and teeth with plaque visible (P=<.001).
There were no statistically significant differences in oral mucositis
among different conditioning regimens (P=0.306), donor (P=0.741),
gender (0.825) or type of transplant (0.425). Dry mouth and altered
taste sensation were the most common oral complications (85%, 83%
respectively) followed by throat pain (68%).
Conclusions
31. MULTICENTER CLINICAL STUDY TO ASSESS ORAL
COMPLICATIONS OF CONDITIONING THERAPY AND STEM
CELL TRANSPLANTATION - ORASTEM STUDY
Samim F1 , Aluck A 2, Brennan M.T.3, von Bültzingslöwen I4, Williams
P.M. 1, 2 .
University of British Columbia, Faculty of Dentistry, Vancouver, BC 2BC
Cancer Agency, Vancouver, British Columbia, Canada2, 3Department of
Oral Medicine, Carolinas Medical Center, Charlotte, NC, 4Sahlgrenska
Academy, Göteborg, Sweden.
1
Objectives
The overall aim of this prospective international observational
multicenter study is to establish the nature, incidence, severity and
temporal relationship of oral complications related to high dose
48
Level of oral hygiene has a strong relationship with oral mucositis and its
severities. This study is in progress and interim result will be presented.
32. MYELOABLATIVE BUSULFAN CONDITIONING
REGIMENS: SINGLE CENTER EXPERIENCE OF PATIENTS
WITH MYELOID NEOPLASMS
Raj R V, Dozeman L, Button A, Silverman M, University of Iowa, Iowa City
Background
The use of Busulfan with Cyclophosphamide (BuCy) as a myeloablative
conditioning regimen for allogeneic stem cell transplantation (alloSCT) is limited by significant regimen-related toxicity. Several reports
suggest that the combination of Busulfan and Fludarabine (BuFlu)
in ablative doses may provide effective control of myeloid neoplasms
with less toxicity. The aim of the study was to compare outcomes of
two myeloablative Busulfan-containing regimens in a cohort of 83
consecutive patients (pts) who received allo-SCT for myeloid disease
Methods
Retrospective analysis of pts with myeloid neoplasms (AML, MDS or CML)
who underwent allo-SCT after myeloablative conditioning with BuFlu or
BuCy between 2006 and 2012 was done. Forty-five pts received BuFlu
and 38 received BuCy. Median age at transplant was 58 (range 22-68) in
the BuFlu group and 53 (range 19-68) in BuCy. Disease risk by CIBMTR
classification was high in 27 (60%) pts in BuFlu group and 10 (26.3%)
in BuCy. GVHD prophylaxis consisted of tacrolimus and methotrexate
in all pts in the BuFlu group and 82% in the BuCY group. Seven pts in
BuCy received cyclosporine and mycophenolate. Thymoglobulin was
administered in unrelated and mismatched donor transplants.
Results
All pts engrafted except 1 in the BuCy group. Mortality at day 100 posttransplant was 4.4% in BuFlu and 21% in the BuCy (p=0.038). Grade
3 or 4 GVHD was diagnosed in 6.6% in BuFlu and 21% in BuCy. After
a median follow-up of 554 days the risk of relapse or death for pts in
the BuCy group was 2.17 times (95% CI 1.082-4.35, p=0.028) higher
than for pts in BuFlu. The trend for overall survival was better in the
BuFlu group compared to BuCy (HR -1.97, 95%CI 0.97-3.97, p=0.059).
Relapse-free survival was also favored in BuFlu pts.
Conclusions
With the caveats of not being a randomized study, we found that
conditioning with BuFlu is better tolerated, has better 100-day mortality,
improved time to progression and overall survival, in spite of the fact
that the pts in the BuCy group had a higher CIBMTR risk score.
33. PROFILING STUDY CHARACTERISTICS IN ALLOGENEIC
HEMATOPOIETIC CELL TRANSPLANTATION: A LIMITED
SCOPING REVIEW
Sophie Pilon1, Daniel Jedrysiak1, Jason Tay1,2,3, Dawn Sheppard1,2,3,
Christopher Bredeson1,2,3, David Allan1,2,3
Blood and Marrow Transplant Program, The Ottawa Hospital; 2 Department of Medicine,
University of Ottawa and 3 Ottawa Hospital Research Institute, Ottawa, ON.
and other characteristics, comparing the study characteristics for
specific aspects of care related to allogeneic HSCT to identify trends and
areas in need of greater study.
Results
A total of 116 articles were reviewed in detail by 2 investigators. 39%
of the papers in our study were conducted in North America. 42% of
the papers analyzed adult patients, 7% analyzed pediatric patients,
and 51% analyzed both. 46 studies were prospective, including 4
RCTs. 75 articles were retrospective studies with 36 involving multiple
centers. Areas that have been studied with RCT include conditioning
regimen (n=1), graft-versus-host- disease (n=1) and infections (n=2).
Multi-center observational studies (registry-based) have emerged as
a powerful tool in the study of care related to allogeneic HSCT and
36 studies were identified (31% of studies). The most studied areas in
this study type involved donor selection, source of cells (BM vs PB) and
conditioning regimens while transfusion practices and management of
infections or GVHD were rarely addressed.
Conclusions
Our findings suggest retrospective observational studies performed
through cooperative registries represent a feasible and informative
method of studying various aspects of care in allogeneic transplantation
such as donor selection, source of cells, and conditioning regimens.
However, interventions for the management of infections or GVHD
may be best addressed using prospective RCTs, which remains scarce.
Moreover, our limited scoping review provides a potential tool for the
comparison of concordance between RCTs and observational studies.
34. PROJECT COBRA: COMPENDIUM OF BEST EVIDENCE
FROM RCTS IN ALLOGENEIC HEMATOPOIETIC CELL
TRANSPLANTATION
Abhinav Iyengar1, Risa Schorr2, Nicholas Scrivens3, David Moher4, Dawn
Sheppard1,3,4, Christopher Bredeson1,3,4, Jason Tay1,3,4 & David Allan1,3
Division of Hematology, Department of Medicine, University of Ottawa; 2Library and
Information Services and 3Blood and Marrow Transplant Program, The Ottawa Hospital; and
4
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa ON Canada.
1
1
Background
Evidence-based practice patterns in allogeneic hematopoietic cell
transplantation (HCT) is reliant on observational clinical studies and
randomized controlled trials (RCTs). The extent to which specific aspects
of care in allogeneic HCT have been studied and the types of studies
that have been performed remains incompletely documented.
Methods
Studies in allogeneic HSCT were systematically identified from selected
journals between 2010–2011. We assessed these articles for design
Background
Allogeneic hematopoietic cell transplantation (AHCT) represents a
multi-faceted and complex health care intervention. The strength of
evidence from randomized controlled trials regarding specific aspects of
care in AHCT remains imprecise. Through a systematic scoping review of
the literature, we sought to create a compendium of best evidence from
randomized controlled trials (RCTs) addressing aspects of AHCT (coined
COBRA). The chief goal of Project COBRA is to provide a foundation of
evidence that can allow us to identify areas of transplant care that are
understudied, assess the quality of evidence that underpins intuitional
practice in AHCT and to plan future trials.
49
Methods
A systematic scoping review of published studies was performed by
searching multiple electronic databases (Medline, EMBASE, Cochrane
Reviews) using the following search concepts: RCTs and AHCT. Relevant
articles were reviewed in full and trial level data extracted accordingly
Results: We identified over 11,000 articles. After screening for relevance
and removing duplicates, 627 articles were included in the compendium
and were classified into specific aspects of AHCT care. RCTs were
identified for the following aspects of care in AHCT: collection and/or
harvesting of cells (n=46), conditioning regimens (n=50), prevention
and/or treatment of GVHD (n=106), transfusion-related interventions
(n=20), prevention and/or treatment of infections (n=228), prevention
and/or treatment of sinusoidal obstruction syndrome (n=15), prevention
and/or treatment of bronchiolitis obliterans (n=11), and others that
included studies of exercise, anti-emetics, mucositis and nutrition
(n=151).
Conclusion
It appears there is a maldistribution of RCTs in AHCT with a
disproportionate number of studies addressing anti-infective strategies
and relatively few RCTs addressing other important aspects of care
such as transfusion practices. Project COBRA provides a powerful
compendium of best evidence that provides a foundation for performing
meta-analyses, assessing the quality of current evidence, the validity of
current institutional practices and for planning future trials in AHCT.
35. A SYSTEMATIC REVIEW OF PRECLINICAL STUDIES
ON THE THERAPEUTIC POTENTIAL OF MESENCHYMAL
STROMAL CELL-DERIVED MICROVESICLES
Celine Akyurekli1, Yevgeniya Le1,3, Richard B. Richardson3, Jason Tay1,2,
David S. Allan1,2
Regenerative Medicine Program, Ottawa Hospital Research Institute, and 2 Department of
Medicine, University of Ottawa, Ottawa ON Canada, 3 Atomic Energy of Canada Limited,
Chalk River, ON
1
Background
The therapeutic potential of mesenchymal stromal cells (MSCs) may
be largely mediated by paracrine factors contained in membrane
bound microvesicles released from endosomes. A systematic review of
preclinical studies was performed to identify strategic aspects that could
accelerate clinical translation of MSC-derived microvesicle therapy in
regenerative medicine.
Methods
Using the OVID interface, we performed an electronic database search
(MEDLINE, EMBASE, PUBMED) between 1946 and July 2013 using the
following search concepts: MSC-derived microvesicles, therapy and
animal models. Subsequently, articles were screened for relevance, with
50
relevant articles reviewed in full and study level data extracted using a
standardized extraction form. The results of this extracted was collated
accordingly.
Results
We identified 190 published articles and after screening for relevance,
a total of 17 controlled studies underwent comprehensive review and
data extraction. Thirteen studies addressed the regenerative potential
following organ injury (6 studies were included on acute kidney injury,
4 on myocardial infarction and reperfusion injury, 1 study of hind limb
ischemia, 1 study of liver injury, and 1 study of hypoxic lung injury)
and 4 studies addressed immunological effects of MSC-derived
microvesicles on inhibiting tumor growth. Therapeutic intervention
involved isolated exosomes (40 – 100 nm) in 8 studies, while 9 studies
tested microvesicles (< 1000 nm). The 13 studies of tissue regeneration
all reported that treatment with MSC-derived microvesicles improved
at least one parameter associated with organ dysfunction. Three of 4
studies addressing the inhibition of tumor growth reported benefit. Four
studies compared MSC-derived microvesicles with MSCs and reported
equivalent (2 studies) or improved (2 studies) outcomes with MSCderived microvesicles.
Conclusions
The use of MSC-derived microvesicles is strongly associated with
improved organ function following injury and may be useful for inhibiting
tumor growth in preclinical animal models. Progress towards clinical
trials is warranted to assess feasibility and safety of this therapeutic
approach in humans.
36. CHRONIC GRAFT-VERSUS-HOST DISEASE IS A
SIGNIFICANT RISK FACTOR FOR THE DEVELOPMENT OF
NOCARDIOSIS IN ALLOGENEIC HEMATOPOIETIC STEM
CELL TRANSPLANT RECIPIENTS: A MATCHED CASECONTROL STUDY OF RISK FACTORS, CLINICAL FEATURES
AND OUTCOMES
Nadia M. Bambace, MD, FRCPC¹, Louise Poirier, MD, FRCPC², Imran
Ahmad, MD, M.SC¹., Jean Roy MD, FRCPC¹ , Miguel Chagnon, M.SC.,
P.Stat ³ and Silvy Lachance, MD, FRCPC¹
1
Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont, Montreal,2Department
of Infectious Diseases, Hôpital Maisonneuve-Rosemont, Montreal, 3Biostatics Unit,
Université de Montréal, Montreal, Canada.
Introduction
Despite indisputable advances in supportive care, opportunistic
infections (OI) remain an important cause of morbidity and mortality
among hematopoietic stem cell transplant (HSCT) recipients. The
incidence of disseminated nocardiosis, a relatively infrequent infection
involving the airways, skin and the central nervous system (CNS) has
increased significantly among this population within the last decade.
The risk factors and outcomes of nocardial infection in HSCT recipients
remain undefined to date.
Methods
We performed a case-control study to identify the risk factors and
outcomes of infection with Nocardia among 433 allogeneic HSCT
recipients transplanted between January 2007 and December 2012 at
Maisonneuve-Rosemont Hospital. Fourteen cases of Nocardia infection
were identified. Control subjects were matched for age (+/- 5 years),
transplant type, and date of transplant (+/- 6 months).
Results
The 6-year cumulative incidence of nocardiosis was 3.2%. Fifty
percent had disseminated disease with documented CNS involvement
in 21% of cases. Infection clustered in autumn and occurred at a
median of 351 days after HSCT. N. farcinica was the most commonly
isolated strain (29%). Copathogens were detected in 71% of cultures.
Nocardia isolates were often resistant to several antimicrobials, with
the exception of amikacin, imipenem and linezolid, for which 100%
susceptibility was documented. The resistance rate to TMP-SMZ was
33%. Although there was no difference in overall survival (OS) (37%
vs. 51%, p = .05), the 2-year OS following HSCT was significantly
reduced in the Nocardia cohort (78% vs. 100%, p=.01) and better
captures the mortality associated with this infection. All case patients
had extensive chronic GVHD and had received treatment with high dose
corticosteroids and calcineurin inhibitors in the preceding 6 months.
Rituximab treatment within the last year was also associated with the
development of this infection (p = .001). On univariate analysis, steroidinduced diabetes mellitus (p= < .001), bronchiolitis obliterans syndrome
(BOS) (p= .008), lymphopenia (p = .043) and opportunistic infection in
the previous 6 months (p< .001) emerged as significant variables. We
observed no association with donor type, graft size, stem cell source,
type of GVHD prophylaxis, conditioning regimen/intensity, disease risk,
and engraftment time. Outpatient non-myeloablative transplant was
not associated with an increased probability of infection. Interestingly,
steroid-refractory chronic GVHD was not associated with increased risk
of nocardiosis, suggesting that steroid therapy and not GVHD severity
represents the most powerful predictor of infection.
Conclusion
Our study represents the only contemporary series of Nocardia infection
arising in HSCT recipients, and establishes chronic GVHD as the major
risk factor. Clinicians should have an elevated clinical index of suspicion
for nocardiosis in chronic GVHD patients receiving prolonged high doses
of steroids or rituximab, particularly between October and December.
Patients with BOS may represent a particularly vulnerable subpopulation in
which chemoprophylaxis may be considered. Lastly, our results challenge
the use of TMP-SMZ as initial therapy, given the elevated resistance rates
to this agent, which may have developed as a result of microbial selection
from current transplant prophylactic practices.
37. SERUM ALBUMIN LEVEL < 32 G/L ON DAY 30 CAN
PREDICT HIGHER RISK OF NON-RELAPSE MORTALITY
IN ACUTE LYMPHOBLASTIC LEUKEMIA FOLLOWING
ALLOGENEIC STEM CELL TRANSPLANTATION
Feras Alfraih,1,2 Jieun Uhm,1 Vikas Gupta,1 John Kuruvilla,1 Jeffrey H.
Lipton,1 Hans A. Messner1, Matthew Seftel1 and Dennis (Dong Hwan)
Kim,1*
1
Allogeneic Blood and Marrow Transplant Program, Department of Department of Medical
Oncology and Hematology, Princess Margaret Hospital, University Health Network,
University of Toronto, Toronto, Canada, 2 Adult Hematology and Bone Marrow Transplant
Program, King Faisal Hospital and Research Centre, Riyadh, Saudi Arabia
Introduction
It is extremely significant to predict hematopoietic stem cell transplant
(HSCTs) outcomes using a biomarker. In this study, we attempted to
evaluate the impact of post-transplant serum albumin on outcomes in
patients with acute lymphoblastic leukemia (ALL).
Methods
123 patients with ALL receiving HSCTs between year 1999 and 2012
at our center were evaluated for post-transplant serum albumin levels
and their correlation with transplant’s outcome. The level of serum
albumin was retrospectively retrieved in certain time point ± 3 days at 1
month pre HSCT and weekly after transplantation for first 3 months. 100
patients had available serum albumin levels. The ROC analyses were
used to determine the most statistically significant cutoff level of serum
albumin correlating with NRM at 1 year. Level of 32 g/l at 4 weeks
post HSCT was suggested as the best cutoff for further analysis. Patients
were stratified into low versus high albumin level group.
Results
Median age for all patients is 37 with range of (17-61). 35% were female.
Related donors were 57%. Matched donors were 83%. 71% were in 1st
complete remission. 37% were Philadelphia chromosome positive. GVHD
prophylaxis was CSA/MTX 60%, CSA/MMF 22%. Conditioning regimen
was myeloablative in 95%. 61% received peripheral blood stem cells.
With a median follow-up of 60 months for survivors (range 21 to 100
months), 61% patients showed albumin level ≥ 32g/l at day 30 while
39% showed dropped albumin level <32 g/l at day 30.
OS rate at 2 years was 61% in high albumin group versus 23% in low
albumin group (p < 0.001). NRM rate was 62% in high albumin group
versus 17% in low albumin group (p < 0.001). However, no difference
of relapse incidence was noted between the two groups.
Cumulative incidence of overall acute GVHD, grades 2/4, grades 3/4 at
day 120 and overall chronic GVHD at 2 years was 67%, 59%, 16% and
45% in high albumin group versus 72%, 70%, 49% and 39% in low
albumin group, suggesting higher incidence of grade 3/4 acute GVHD
in low albumin group.
51
In multivariate analysis, serum albumin level < 32 g/l at 4 weeks was
confirmed as an independent adverse risk factor for NRM (p=0.04,
HR 2.81) together with acute GVHD grades 3/4 (p 0.01, HR 3.79)
and chronic GVHD (p≤0.001, HR 0.21). For OS, albumin level was not
confirmed as an independent risk factor, but acute GVHD grade 3/4 (p<
0.001, HR 3.36) and chronic GVHD (p <0.001, HR 0.008) were found
to be independent factors. For relapse, chronic GVHD grade 3-4 was the
only independent prognostic factor (p <0.001, HR 0.27).
Conclusion
The present study suggested that 1) serum albumin level less than 32
g/l at day 30 can predicts higher risk of NRM and 2) dropped serum
albumin might be affected by in part the occurrence of severe acute
GVHD, and by independent mechanism of gut GVHD. Further study is
strongly warranted to confirm the prognostic role of serum albumin level
on transplant outcomes in a prospectively designed study.
Results
There were significant differences between original and replication
sets in baseline characteristics (age, underlying disease, conditioning,
GvHD prophylaxis, graft source, donor type, incidences of GvHD and
CMV viremia) in accordance to the changes over a decade in allo-HCT
procedures.
The cumulative incidence of LGL lymphocytosis at 3 years was 21.8%
in the original set and 11.7% in the replication set (P < 0.001). Median
onset of LGL lymphocytosis was 362 days after HCT in the original set
and 223 days in the replication set. Patients with LGL lymphocytosis
showed a persistent elevation of lymphocyte count compared to patients
without LGL lymphocytosis (P < 0.001).
Patients with LGL lymphocytosis showed a higher overall survival (OS)
(86.4% vs 46.1%, P < 0.001, Fig. A) and lower non-relapse mortality
(NRM) (10.5% vs 36.3%, P < 0.001, Fig. B) at 3 years. No significant
difference was found in relapse incidence according to the development
of LGL lymphocytosis (13.9% vs 19.6%, P = 0.25).
Multivariable analysis confirmed the favourable impact of LGL
lymphocytosis on OS (HR 0.30, P = 0.02) and a trend towards lower NRM
(HR 0.27, P < 0.001, original set; HR 0.50, P = 0.22, replication set). No
effect of LGL lymphocytosis on relapse incidence was demonstrated (HR
1.24, P = 0.37, original set; HR 0.53, P = 0.29, replication set).
Patients with LGL lymphocytosis showed a trend towards a higher
incidence of IST cessation after cGvHD: 63.6% at 7 years vs 53.4% in
patients without LGL lymphocytosis, P = 0.07.
38. VALIDATION OF FAVOURABLE IMPACT OF LARGE
GRANULAR LYMPHOCYTOSIS AFTER ALLOGENEIC
M Poch Martell1, J Uhm1, N Alam1, V Gupta1, J Kuruvilla1, JH Lipton1, M
Seftel1, HA Messner1 and D Kim1
Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre,
University Health Network, University of Toronto
1
Introduction
We previously reported on the incidence of large granular lymphocytosis
(LGL) following allogeneic hematopoietic cell transplantation (allo-HCT),
its favourable impact on outcome and the predictive factors associated
with its development (D Kim, BMT, 2013). In the current study we aimed
to validate our previous findings in an independent set of patients.
Methods
All 408 patients undergoing allo-HCT at Princess Margaret Cancer Centre,
Toronto, from 2007 to 2012 (replication set) were included retrospectively.
Data from the previously reported set of patients undergoing allo-HCT
from 2000 to 2007 (n = 418) (original set) were updated.
52
The previously identified predictive factors for the development of LGL
lymphocytosis were replicated: higher incidence of LGL lymphocytosis
with 1) CMV seropositive recipients (29.6% vs 5.1%, P < 0.001); 2)
CMV viremia (31.0% vs 8.9%, P < 0.001) and 3) chronic GvHD (28.2%,
vs 5.0%, P < 0.001).
Conclusion
The favourable impact of LGL lymphocytosis following allo-HCT in OS
and NRM, as well as the predictive factors for the development of LGL
lymphocytosis were successfully validated in an independent cohort
of patients. No impact of LGL lymphocytosis on relapse incidence was
noted. The difference in transplantation procedures between the two
cohorts, such as GvHD prophylaxis/T-cell depletion, may explain the
lower incidence of LGL lymphocytosis in the replication cohort. Patients
with LGL lymphocytosis showed a trend towards a higher incidence of
IST cessation after cGvHD, which may explain the lower NRM. Patients
with LGL lymphocytosis showed a persistent elevation of lymphocyte
count and had an indolent course.
OS and NRM according to the development of LGL lymphocytosis
transplant. One year after transplant he developed bilateral lower
extremity edema and was found to have nephrotic range proteinuria
of 24.5 g over 24 hours. He underwent renal biopsy which showed
minimal change disease. He was started on high-dose steroids with
good clinical response.
All three patients underwent workup for other causes of nephrotic
syndrome including hepatitis B and C serology which was negative.
Conclusion
39. NEPHROTIC RANGE PROTEINURIA AS A POSSIBLE
MANIFESTATION OF CHRONIC GRAFT-VERSUS-HOST
DISEASE
Raj R V, Silverman M M, Division of Hematology-Oncology & Blood and Marrow
transplantation, University of Iowa, Iowa City
Background
Nephrotic syndrome after allogeneic stem cell transplant is a rare
renal complication. There have been several case series of nephrotic
range proteinuria as a possible manifestation of chronic graft-versushost disease. The common pathological findings in a renal biopsy for
such patients are membranous glomerulonephritis and minimal change
disease. Nephrotic range proteinuria is not included as a manifestation
of chronic graft-versus-host disease in the NIH consensus criteria.
Methods
We report our clinical experience with three patients who developed
nephrotic range proteinuria after allogeneic stem cell transplantation.
Results
Patient 1: 55 year old male who underwent sibling matched peripheral
blood stem cell transplant for chronic myelomonocytic leukemia.
Eighteen months after transplant he developed disease relapse and
underwent donor lymphocyte infusion (DLI). Three months after DLI he
developed nephrotic range proteinuria of 14.5 g in 24-hour urine. There
were associated skin and eye manifestations of chronic GVHD at the
same time. Serum creatinine at the time of diagnosis was 1.5 mg / dl.
He was treated with high-dose prednisone with good clinical response.
Patient 2: 53 year old male who underwent sibling matched peripheral
blood stem cell transplant for multiple myeloma. Two years after
transplant he was on high-dose steroids for skin and liver GVHD. Six
months after his steroids were tapered and stopped, he developed
generalized edema and was found to have proteinuria of 8.4 g over 24
hours. He was restarted on high-dose steroids with complete resolution
of proteinuria.
Patient 3: 46 year old male with diagnosis of acute lymphocytic
leukemia underwent matched unrelated peripheral blood stem cell
Nephrotic range proteinuria appears to be a manifestation of chronic
graft-versus-host and it should be considered as a renal manifestation
of chronic graft-versus-host disease. Monitoring for proteinuria in postallogeneic stem cell transplant recipients is warranted. Inclusion of
nephrotic range proteinuria as a manifestation of chronic graft-versushost disease in the NIH consensus criteria may help for early diagnosis
and prompt treatment in allogeneic stem cell transplant recipients.
40. IMPORTANCE OF MONITORING COMPLETE
MOLECULAR REMISSION IN PEDIATRIC ACUTE MYELOID
LEUKEMIA BEARING MLL REARRANGEMENTS: FOCUS ON
THE RARE AND NOT ALWAYS “GOOD PROGNOSIS” T(1;11)
(Q21;Q23) TRANSLOCATION
Pécheux L.1, Dormoy-Raclet V.2, Couture F.2, Bittencourt H.1, Cellot S.1,2
Pediatric Hemato-oncology and HSCT Unit, 2 Molecular Biology Laboratory, CHU-SaintJustine, Montréal
1
Abstract Body
MLL gene is frequently rearranged with various fusion partners in high
risk pediatric acute myeloid leukemia (AML). While the results of a
recent study have shown a particularly good prognostic when MLL is
rearranged with MLLT11 on 1q21 (previously called AF1q) compared to
other partners, some authors have also reported MLL-MLLT11 pediatric
AML cases with relapse and death, illustrating that all these MLLMLLT11 AML are maybe not equal in prognosis. Monitoring treatment
response through detection of remaining leukemic cells using highly
sensitive methods is already effective to improve patient outcome in
several leukemia subtypes.
Here we report the case of a young patient with MLL-MLLT11 AML of
FAB-M2 subtype and CNS involvement. While morphological remission
was documented after the second induction (presence of 7% of
blasts after induction 1 and less than 5% after induction 2) and while
absence of blasts was demonstrated after the first consolidation using
immunophenotypic analysis (kinetics of decrease in the percentage of
immunophenotypic blasts: 19% post induction 1, 1.3% post induction
2, and none after consolidation 1), the persistence of detectable MLLfusion transcript using specific reverse transcription polymerase chain
reaction (RT-PCR) after consolidation 1 justified treatment intensification
with allogeneic hematopoietic stem cell transplantation (HSCT). As
53
the MLL-fusion transcript was still detectable after HSCT despite full
hematologic recovery, 100% donor chimerism and maintenance of
morphological and immunophenotypic remission, the patient received
donor lymphocyte infusions (DLI) to achieve sustained complete
molecular remission. Five months after the second DLI, the patient is
well and the MLL-fusion transcript specific PCR remains negative.
In MLL-rearranged leukemia and other high risk leukemia, sensitive
detection of fusion transcripts using RT-PCR during and after completion
of planned therapy, is not only prognostic as persistence of MLL-fusion
transcript may be indicative of short-term relapse, but can also identify
patients that could benefit from additional treatment to achieve
complete molecular remission.
41. RELAPSE AFTER AUTOLOGOUS STEM CELL
TRANSPLANTATION FOR AGGRESSIVE NHL: CLINICAL
CHARACTERISTICS AND FACTORS PREDICTING OUTCOME
Shane Gangatharan1, John Kuruvilla1, Armand Keating1, Vishal Kukreti1,
Rodger Tiedemann1, Michael Crump1
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto
1
After relapse post-ASCT, management was palliative in 4 patients, IV
chemotherapy in 8 and oral in 7. Ten patients received a novel agent
most of which were as part of a clinical trial, the most common being
panobinostat (n=6). Two patients had further salvage chemotherapy
followed by allogeneic stem cell transplant. Radiotherapy was used in
22 (56.4%) patients which in 7 was the only treatment used.
With median follow-up 23 months after post-ASCT relapse, 25 patients
have died. Median overall survival (OS) after relapse was 8.5 months
(2-year OS 27.6%). Median OS according to second-line IPI: high 4.1 months, intermediate - 9.5 months, low – not reached (p=0.09).
Relapse within 1 year of primary therapy (p=0.42) and previous use of
rituximab (p=0.86) were not associated with OS. Time to relapse after
ASCT <6 months predicted survival after relapse (2-year OS 17.4% v
55.6%, p=0.03). At time of relapse post-ASCT, stage (p=0.43), bone
marrow involvement (p=0.69) and extranodal sites (p=0.53) did not
predict OS. No intervention after relapse significantly predicted OS.
Radiotherapy was associated with improved survival (median OS 9.46
months v 4.15 months) though not significant (p=0.07).
Conclusion
Background
High-dose chemotherapy and autologous stem cell transplantation
(ASCT) is the only curative therapy for relapsed/refractory aggressive
NHL. Despite this 30-50% will still relapse, predicted by second-line
IPI, initial therapy with rituximab and early relapse. There is no standard
of care for the management of patients who relapse post-ASCT, and
survival has been <1 year. We aim to review the patterns of relapse
post-ASCT and examine factors influencing outcome.
Methods
The transplant database at Princess Margaret Hospital was interrogated
for patients undergoing ASCT from 2007-2011 for relapsed/refractory
aggressive NHL. Retrospective chart review identified patients who
relapsed post-ASCT and data was collected on pre- and post-transplant
characteristics, therapies and outcome.
Results
39 patients were identified with relapse post-ASCT (29 DLBCL, 7
transformed, 3 T-cell). Median age 55 (range 32-67). Prior to ASCT,
second-line IPI: 0 – 7.7%, 1 – 15.4%, 2 – 46.1%, 3 – 28.2%. 59%
relapsed within 12 months after initial therapy. Of B-cell lymphomas,
86.1% received rituximab with primary therapy.
Median time to relapse after ASCT was 3 months (range 1-52). Stage at
relapse after ASCT: I – 17.9%, II – 23.1%, III – 7.7%, IV – 51.3%. Bone
marrow was involved in 12/39 (30.8%). Extranodal sites were involved
in 18/39 (46.2%); common sites being bone 6, skin 5, lung 2, adrenal
2, CNS 2, liver 2. Time to relapse after ASCT was not predicted by
second-line IPI, early relapse after primary therapy, or primary treatment
54
incorporating rituximab.
In patients who relapse post-ASCT, second-line IPI and early relapse
after ASCT predicts survival, while clinical presentation of stage, bone
marrow involvement and extranodal sites at relapse do not. Additional
agents with activity in this patient population are needed; where
feasible, radiotherapy should be considered for patients with localized
recurrence.
42. ISOLATED PENILE MEATAL CHRONIC GVHD IN A BOY
FOLLOWING ALLOGENEIC TRANSPLANT FOR JMML
Spicer C1, MacLellan D1,2, Fraser R1,3, Crooks BNA1,4, Fernandez CV1,4.
1
IWK Health Centre, 2Department of Urology, 3Department of
Pathology, 4Department of Pediatrics, Dalhousie University.
Background
Graft versus host disease (GVHD) is a major complication following
allogeneic hemaotopoietic stem cell transplant (HSCT). Chronic GVHD
can occur in any organ in the body. Genital GVHD is less commonly
reported than areas such as liver, gastrointestinal tract and skin. Genital
GVHD occurs in at least a third of women. Up to 20% of men have cGVHD
of the penis including balanoposthitis, lichen sclerosis-like lesions and
phimosis. It is very rarely described in pediatric male patients.
Case Report
A 10 year old male was diagnosed with juvenile myelomonocytic
leukemia (JMML). He underwent a living unrelated donor transplant
(LURD) with a preparative regimen of Busulfan, Cyclophosphamide
and Melphalan. He received Cyclosporin and Methotrexate as GVHD
prophylaxis. He developed grade III acute GVHD involving skin, liver
and GI tract, and subsequent extensive chronic GVHD (eyes, mouth,
skin, liver, GI tract) that required a variety of immunosuppression
including cyclosporine A, steroids, tacrolimus, sirolimus over a 2 year
period, including eventually Extracorpeal Photopheresis (ECP). The
ECP was given 2 days every 2 weeks, for one year. He was tapered
off systemic immunosuppressive medications 6 months into the ECP,
and there was no evidence of active cGVHD at completion of treatment
with ECP. Approximately 3 months after stopping the ECP he developed
genitourinary symptoms which included hematuria, urinary hesitancy,
straining to void, and narrowing of the urinary stream. The glans penis
was clinically normal except for meatal erythema and a pin-point urinary
meatus. He was diagnosed with meatal stenosis with an abnormal
uroflow study consistent with obstruction. Glans biopsy at the time of
meatotomy demonstrated active cGVHD. There were no other signs of
active GVHD in this patient, except for sequelae of ocular GVHD, for
which he is receiving topical Cyclosporin A and lubricant drops. He had
recurrence of his symptoms within several weeks after meatotomy and
recurrent meatal stenosis was confirmed on examination. He has been
successfully managed using topical steroid as lubrication on a urinary
catheter, with twice daily catheter dilations, without reinitiating any
systemic immunosuppression.
single agent, escalated dose TBI (ED-TBI) (18Gy) followed by an alloHCT.
Methods
Patients (18-60 years old) with rAML and an HLA MRD or MUD received
an alloHCT after ED-TBI, 2.25Gy BID (days -4 to -1) x 8 fractions (total
18Gy). Donor cells were infused on day 0. Graft vs. host disease (GVHD)
prophylaxis consisted of tacrolimus (day -3 - 90) and mycophenolate
mofetil (MMF) (day 1 - 60). The primary end point, treatment related
mortality (TRM), was measured using the CTCAE v.4 and the LENTSOMA scales.
Results
Patients: Seven have undergone an alloBMT (d8 - >365). Two patients
had rAML following 2-4 inductions. One patient relapsed during
consolidation. Another patient had rAML (secondary) after one
induction attempt and three had relapsed (<6 months) rAML. Two
also had CNS disease, treated prior to transplant. All had persistent
leukemia at the start of ED-TBI, with 5 out of 7 having > 50% blast cells
in the marrow. Three patients required moderate doses of chemotherapy
(daunorubicin, cytarabine, azacitidine or hydroxyurea) to maintain their
disease prior to alloHCT.
Toxicity:
Conclusion
Isolated meatal cGVHD in a child has not, to our knowledge, been
previously reported. It is our hope that sharing this case report will
emphasize that genital GVHD is a potential complication among
pediatric and adult HSCT patients and the importance of regular
genitourinary assessment in males as well as females.
43. ESCALATED DOSE-TOTAL BODY IRRADIATION (18GY)
FOLLOWED BY AN ALLOGENEIC CELL TRANSPLANTATION
FOR THE TREATMENT OF REFRACTORY ACUTE MYELOID
LEUKEMIA: EARLY RESULTS
Sultan Altouri., Harry Atkins, David Allan, Jason Tay, Mai Le, Linda
Hamelin, Dawn Sheppard, Lothar Huebsch, Tim Ramsay, Christopher
Bredeson, Rajiv Samant, Mitchell Sabloff
Blood and Marrow Transplant Program, The Ottawa Hospital.
Introduction
Refractory AML (rAML) has a poor overall survival (OS) after a standard
allogeneic hematopoietic cell transplantation (alloHCT). Higher doses
of TBI (15.75 vs. 12Gy) have been shown to reduce AML relapse for
patients in complete remission (CR). Preliminary work, replacing
cyclophosphamide in the conditioning, with escalated doses of TBI
(16Gy), followed by an HLA matched related or unrelated donor (MRD
or MUD)-alloHCT has resulted in long-term remissions in 2 out of 4
patients. Based on these encouraging results we initiated and report on
the preliminary results of a prospective phase 2 ethics approved study of
Early (<30 days): Two patients had grade 3 mucositis. Two patients
required parenteral feeding. One patient experienced reversible venoocclusive disease. All patients developed diarrhea. All of them resolved.
Late (>30 days): Two patients suffered grade 3 dehydration, requiring
prolonged intravenous hydration (days 37-107). Two patients had CMV
reactivation at days 39 and 60 and were treated with ganciclovir. One
patient developed asymptomatic 250 cc reduction of lung volumes with
a restrictive pattern on PFT.
Engraftment: Neutrophil engraftment occurred between days 15-25 and
the patients were discharged from the hospital between days 19-30.
GVHD: Acute GVHD occurred in 1 patient <day 30, treated successfully
with prednisone. Chronic (cGVHD) occurred in all patients, involving the
GI tract (n=2) and liver (n=2). One patient had persistent cGVHD at
one year involving the mouth and skin. Four did not complete tapering
immune-suppression before relapse.
Response: Circulating blast cells, at the time to alloHCT, all were cleared
by day 1 in 5 patients. Two patients are in continuous CR on days 40
and 464. Four patients have relapsed at days 96, 110, 139 and 392 and
died on days 106, 145, 257 and 397 respectively.
Conclusion
To date, ED-TBI (18Gy) followed by an alloHCT has a toxicity profile
which is comparable to other alloHCT conditioning regimens. Safety and
efficacy are continuing to be assessed with a goal to recruit 20 patients.
55
44. PRE-TRANSPLANT REMISSION STATUS AND USE OF
PERIPHERAL BLOOD STEM CELLS CONTRIBUTE TO LONGTERM OUTCOME AFTER MYELOABLATIVE ALLOGENEIC
TRANSPLANT FOR MULTIPLE MYELOMA
in frontline reduced-intensity allogeneic HSCT. We speculate that MA
HSCT could carry a stronger anti-MM effect as an upfront approach
and could be revisited in young and fit patients, especially those with
refractory disease.
Imran Ahmad, Sandra Cohen, Silvy Lachance, Guy Sauvageau, DenisClaude Roy, Lambert Busque, Thomas Kiss, Jean-Sébastien Delisle, Léa
Bernard, Richard LeBlanc, Jean Roy. Blood and Marrow Transplant Program,
Hôpital Maisonneuve-Rosemont and Université de Montréal.
Objective/Rationale
Although myeloablative (MA) allogeneic hematopoietic stem cell
transplantation (HSCT) has cured a minority of patients with MM, it is
now seldom used because of the high transplant mortality. We sought to
describe various outcomes and their predictive factors in MA allogeneic
HSCT recipients at our institution.
Methodology
Data on all patients treated with MA sibling allogeneic HSCT at
Maisonneuve-Rosemont Hospital (HMR) were analyzed retrospectively.
Probabilities of overall survival (OS), progression-free survival (PFS),
relapse, nonrelapse mortality (NRM) and GVHD incidences were
estimated and multivariate analyses conducted on these outcomes.
Results
Between 1990 and 2001, 39 patients (median age 39 years) received
a sibling MA allogeneic HSCT at HMR; 68% had Durie-Salmon stage
III disease and more than half had received more than one line of
treatment. Cytogenetics was not available on these patients. Total
body irradiation-based conditioning was used in 77%; source of stem
cells was G-CSF mobilized peripheral blood (PB) stem cells in 46%.
Incidences of grade II-IV acute and extensive chronic GVHD were 29%
(95%CI: 16-44) and 40% (95%CI: 24-55), respectively. With a median
follow-up of 13 years, incidences of progression and NRM were 43%
(95%CI: 26-59) and 38% (95%CI: 22-54), respectively. Probabilities of
10-year OS and PFS were 33% (95%CI: 19-48) and 29% (95%CI: 1644), respectively. The probability of taking immunosuppressants at 10
years in survivors was 31% (95%CI: 13-58). In multivariate analysis,
PB stem cells and complete remission at transplant were protective for
relapse (HR 0.34, CI: 0.14-0.82), and PFS (HR 0.28, CI: 0.09-0.89),
respectively. Nevertheless, the effect of these variables on OS was nonsignificant. The time-dependent effect of chronic GVHD on various
outcomes was also inconclusive.
56
Figure 1 (left) shows the probability of progression-free survival from
allogeneic transplant, with 95% confidence interval. Figure 2 (right)
shows the stacked cumulative incidences of progression (light grey) and
nonrelapse mortality (dark grey).
45. AN EXPLORATION FOR A MINIMUM CD34+ DOSE
FOR MULTIPLE MYELOMA PATIENTS AGED 65 TO 71
BASED ON AN ASSOCIATION BETWEEN CD34+ DOSE AND
LONG-TERM PLATELET COUNTS FOLLOWING HIGH DOSE
THERAPY
R Martin1, M Ricci2, C Ross3, A MacDonald3 and R Foley.3
Department of Anthropology, University College London, London, United Kingdom, 2School
of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland, 3Department
of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
1
Background
Multiple myeloma is the most common current indication for autologous
stem cell transplantation (auto-SCT). Many centers employ an upper age
limit of 70 years as opposed to clinical trials that typically restrict patients
to 65 years and younger. Transplant is not curative and additional
post transplant therapies are increasingly utilized. The ability to safely
administer post transplant therapy depends on satisfactory blood counts
post auto-SCT. Assessment of platelet recovery may include: (i) time to
initial recovery, (ii) number of platelet transfusions and (iii) long-term
sustained engraftment. In patients 65 and younger platelet recovery
correlates with number of autologous CD34+ progenitor cells infused,
however less data is available for older patients.
Conclusion
Results
In our experience, one third of selected patients with MM are alive 10
years after MA allogeneic HSCT. Achievement of CR before HSCT and
the use of PB stem cells were protective. While being done later in the
course of MM treatment and well before the introduction of newer
therapies, the risk of relapse in our cohort is similar to published results
Our current study (N=113) shows that for a grouping of MM patients
under 65 (34 to 64 years of age) CD34+ dosage significantly correlates
with time to platelet engraftment (P = 0.000), the number of platelet
transfusions before platelet engraftment (P = 0.000), and platelet count at
30 days from CD34+ reinfusion (P = 0.003), but not with platelet counts
at 180 days (P = 0.106) or 360 days (P = 0.148). Conversely, for MM
patients 65-71 years of age CD34+ dose significantly correlates with the
number of platelet transfusions (P = 0.038), and platelet counts at 30
days (P = 0.000), as well as 180 days (P = 0.021), and 360 days (P =
0.005).
Conclusion
These data suggest for “older” MM patients the current minimum target
CD34+ dosage of 2.0×106 cells/kg may be inadequate for maintaining
an adequate platelet count up to 1 year post auto-SCT. Exploratory
analysis from this study suggests a minimum autologous CD34+ dosage
of approximately 3.85×106 cells/kg would be required for older MM
patients to sustain platelets ≥150×109/L at 360 days. The current
minimum dosage of 2.0×106 cells/kg appears to be adequate for longterm platelet engraftment in the under 65 age group.
46. WHEN AN UNEXPECTED EVENT CHANGES TRANSPLANT
INTO FAITH: THE UNTOLD STORY OF CBMTG 0601
Imran Ahmad, Robert Bélanger, Chantal Baron, Sandra Cohen, Jean
Roy and Silvy Lachance. Hematopoietic Cell Transplantation Program, Division
of Hematology and Clinical Oncology, Hôpital Maisonneuve-Rosemont, Université de
Montréal, Montreal, Quebec, Canada.
Introduction
Hematopoietic progenitor cell (HPC) collection in healthy donors carries
a small risk of death (1 in 10,000 donors). We report the case of a
61 year-old female patient with acute myeloid leukemia (AML) in first
remission, randomized under the CBMTG 0601 study, who received a
cadaveric bone marrow (CBM) graft from her 63-year-old brother, who
died before planned collection.
Procedure
On the day after G-CSF mobilization failure was recorded, the donor
became septic and presented cardiorespiratory arrest. Resuscitation
maneuvers were initiated promptly, but death was declared 50 minutes
later. His spouse was informed during resuscitation and consented
to last-resort BM collection. A total of 1 liter of BM was harvested
immediately after resuscitation was stopped. The collected product
was processed by centrifugation for red cell depletion (RCD), due to
bidirectional ABO incompatibility. Total nucleated cell recovery after
RCD was 56 %. (from 3.6 to 2.0 x108 /kg of recipient weight). CD34
count was 0.3 x106 /kg. Cell viability study was adequate. After graft
infusion sterility was established and BM culture yielded the following
results in terms of HPC colonies: 0.2 x104 CFU-GM, 0.0 x104 CFUGEMM and 1.07 x104 BFU-E /kg.
Results
The CBM graft was infused without complication. It was decided not to
infuse the back-up cord blood graft. The recipient was prescribed daily
G-CSF from day +5 and achieved a neutrophil recovery (≥ 0.5 x109/L)
on day +25 after transplantation. Full engraftment of polynuclear
and monuclear cells by short-tandem repeat chimerism study was
achieved on day +37 and remained unimpaired at last follow-up 37
months post-transplant. The recipient later developed de novo chronic
graft-versus-host disease (GVHD) on day +151 with muco-cutaneous
and lower intestinal involvement (biopsies both positive) successfully
treated with prednisone and tacrolimus. At +2 years post CBM
transplantation, the recipient remained ambulatory (Karnofsky score
80%), in continuous complete remission, with ocular, muco-cutaneous
and liver chronic GVHD. BM examination was undertaken several times
after transplantation. No feature of relapse or myelodysplasia could
be seen. Marrow cellularity varied between 5% on day +100, to 25%
at +18 months and up to 40% at +3 year when last evaluated. BM
megakaryocytes remained steadily low. The +3 year BM specimen
confirmed cytogenetic remission and complete donor chimerism.
Conclusion
HCT with CBM is feasible. The possibility of routine collection and
storage of BM from deceased individuals should be further studied,
especially in the wake of ex vivo stem cell expansion technologies. This
could become a novel source for hematopoietic transplantation and
further revive the interest of mixed chimerism induction at time of solid
organ transplant to induce tolerance and improve graft survival from
deceased donors. The most pertinent observation is the extraordinary
capacity of very few CBM stem cells to support long-term hematopoiesis
in our recipient. The most challenging issue is to define how many HPCs
are needed to secure complete and sustained engraftment. After more
than 50 years of hematopoietic transplantation, the definition of the
optimal graft (source and composition) is still open for debate.
47. HIGH PROGRESSION-FREE SURVIVAL AT 10 YEARS
AFTER TANDEM AUTOLOGOUS/NONMYELOABLATIVE
ALLOGENEIC TRANSPLANT FOR MULTIPLE MYELOMA:
IMPACT OF DISEASE STATUS AND CHRONIC GVHD
Imran Ahmad, Sandra Cohen, Silvy Lachance, Thomas Kiss, Guy
Sauvageau, Lambert Busque, Denis-Claude Roy, Jean-Sébastien Delisle,
Léa Bernard, Richard LeBlanc, Jean Roy. Blood and Marrow Transplant
Program, Hôpital Maisonneuve-Rosemont and Université de Montréal.
Objective/Rationale
Allogeneic hematopoietic stem cell transplantation (HSCT) remains
the only curative option for multiple myeloma (MM). However, factors
affecting long-term outcomes have not been clearly defined in tandem
transplant recipients; we sought to identify these in a large prospective
cohort of 93 recipients.
Methodology
Patients with Durie-Salmon stage II-III MM received induction therapy,
57
followed by upfront autologous HSCT and outpatient nonmyeloablative
(NMA) allogeneic HSCT. Conditioning consisted of fludarabine (30 mg/
m2 x 5 days) and cyclophosphamide (30 mg/m2 x 5 days), followed
by infusion of matched sibling donor G-CSF mobilized peripheral blood
stem cells. GVHD prophylaxis included mycophenolate mofetil 1000 mg
BID from day +1 to +50 (no taper) and tacrolimus from day -1 to + 50,
with complete taper by day +100. Probabilities of overall survival (OS)
and progression-free (PFS), relapse, non-relapse mortality (NRM) and
GVHD incidences were estimated, and multivariate analyses performed
on these outcomes.
Results
From May 2001 to March 2010, 93 patients (median age 52 years)
received a tandem HSCT; Durie-Salmon stage III was present in 76%.
Cytogenetics were available in only a minority of patients and could not
be used for analysis. A partial or better response was obtained in 84%
before tandem HSCT. After a median follow-up of 7 years, cumulative
incidences of grade II-IV acute and extensive chronic GVHD were 9%
(95%CI: 4-15) and 85% (95%CI: 75-91), respectively. Cumulative
incidences of NRM and progression were 10% (95%CI: 3-22) and 47%
(95%CI: 37-58). Probabilities of 10-year OS and PFS were 64% (95%CI:
50-74; Fig. 2) and 44% (95%CI: 31-56). In multivariate analysis, at least
stable disease (SD) prior to allogeneic HSCT was a protective factor for
progression and PFS (respectively, HR 0.18, CI: 0.05-0.64, and HR 0.12,
CI: 0.04-0.36). Extensive chronic GVHD was also correlated with a better
PFS (HR 0.39, CI: 0.19-0.80). The most significant protective factor for
OS was at least SD status before allogeneic HSCT (HR 0.15, 95%CI:
0.04-0.56). In survivors, the probability of taking immunosuppressants
was 15% (95%CI: 4-42) at 10 years.
Conclusions
We report an impressive PFS of 44% at 10 years in a large cohort of
93 NMA allogeneic HSCT recipients. Chronic GVHD and disease control
before allogeneic HSCT were both associated with better PFS. We believe
our survival to be superior to other published studies as a result of the
high incidence of chronic GVHD and associated graft-versus-myeloma
effect. Despite the increased risk of chronic GVHD, NRM and prevalence
of immunosuppression at 10 years were low. Agents active against both
MM and GVHD should be prospectively tested to improve long-term
remission rates while reducing the burden of GVHD.
Figure 1 (left) shows the probability of progression-free survival from
allogeneic transplant, with 95% confidence interval. Figure 2 (right)
shows the stacked cumulative incidences of progression (light grey) and
nonrelapse mortality (dark grey).
48. PSEUDOTUMOR CEREBRI ASSOCIATED WITH ALLTRANS RETINOIC ACID TREATMENT IN FEMALE PATIENTS
WITH ACUTE PROMYELOCYTIC LEUKEMIA: A CASE SERIES
Ali M1, 2, 3, Mutahar E1, Sagheir A1, Hashmi H1
1
King Fahad Specialist Hospital – Dammam, KSA. 2 Manitoba Blood and Bone Marrow
Transplant Program. 3 Health Science Centre, Winnipeg, MB
Abstract Body
All-trans retinoic acid (ATRA), a carboxylic acid form of vitamin A was a
revolutionary discovery in the treatment of acute promyelocytic leukemia
(APL) that was found largely by chance in late 80’s. The molecular
hallmark of APL is the presence of a balanced reciprocal translocation
resulting in the PML/RAR-α gene fusion, which represents the target
of ATRA therapy. ATRA is considered to be a safe drug. Pseudotumor
cerebri (PTC) is a rare neurological adverse event of ATRA that was
mainly reported in pediatric population .It is characterized by neurologic
and ocular signs and symptoms of increased intracranial pressure in
the absence of any intracranial pathology or secondary causes of
intracranial hypertension.
Herein we report four cases of young female patients who were
diagnosed with APL and experienced PTC with ATRA treatment. In
three cases fluconazole was taken concurrently. Symptoms completely
subsided with the temporary withdrawal of ATRA and discontinuation
of fluconazole. PTC symptoms did not recur after reintroducing ATRA.
In conclusion, we report a case series of young female patients that
is suggestive of young age, female gender and concurrent use of
fluconazole to be associated with increased risk of developing PTC with
ATRA treatment. Fluconazole should not be used concurrently with
ATRA. We also conclude that the drug could be safely reintroduced once
the symptoms had resolved.
58
49. POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME
ASSOCIATED WITH CYCLOSPORINE USE IN A CHILD
UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM CELLS
TRANSPLANTATION FOR FANCONI ANEMIA: A CASE REPORT
Ali M1, 2, 3, Al-Afghani S1
1
King Fahad Specialist Hospital – Dammam, KSA. 2 Manitoba Blood and Bone Marrow
Transplant Program. 3 Health Science Centre, Winnipeg, MB
Material and Methods
Electronic files were reviewed. Hematological, cytogenetic and molecular
responses were assessed according to blood count and clinical exam,
fluorescent in situ hybridization (FISH) and/or real time quantitative
polymerase chain reaction (RT-Q-PCR), respectively. Classification of
responses was done according to the European Leukemia Network
(ELN) Guidelines.
Results
Abstract Body
Posterior reversible encephalopathy syndrome (PRES) is a neuroclinical
and radiological syndrome that commonly consists of parietooccipital
and posterior frontal cortical and subcortical edema. The neurologic
manifestations are variable, but frequently include headache, altered
mental status, visual disturbances and seizures. Known associated
causative agents include calcineurin inhibitor immunosuppressives such
as tacrolimus and cyclosporine.
We herein report a case of 12 years old boy that was diagnosed
with fanconi anemia and underwent allogeneic Hematopoietic
Stem Cells Transplantation (HSCT) with Fludarabine (35 mg/m2/
day x 5), Cyclophosphamide (10 mg/m2/day x4) and Anti-thymocyte
Globulin (Rabbit ATG) (2.5 mg/kg/day x4). GVHD prophylaxis included
Cyclosporine (65 mg/m2/dose BID) starting day -3 and Mycophenolate
Mofetil 600 mg/ m2/dose BID) starting on day 0. Pre stem cells infusion
course was complicated with ICU admission due to ATG anaphylaxis
reaction. Post stem cells infusion, the patient had elevated blood pressure
and experienced seizure. MRI brain confirmed PRES. Cyclosporine was
discontinued. Patient was put on methylprednisolone 2 mg/kg for GVHD
prophylaxis. The patient did not experience any seizure afterwards.
PRES resolved based on follow up imaging. The patient was started on
tacrolimus with no further PRES episodes.
Although it is a rare complication, it can be concluded that PRES should
be suspected with neurological symptoms in children undergoing HSCT
and taking a calcineurin inhibitor. If confirmed by imaging, rigorous
control of arterial blood pressure and discontinuation of the offending
agent is recommended. We also conclude that it’s safe to rechallenge
the patient with a different calcineurin inhibitor once the PRES resolves.
50. FIRST LINE TYROSINE KINASE INHIBITORS (TKIS)
THERAPY IN CHRONIC MYELOID LEUKEMIA AT THE
CANCER PROGRAM OF WINDSOR REGIONAL HOSPITAL
(2001-2013)
D Sayegh, S Kanjeekal, J Mathews, R Gupta, C Hamm
Cancer Program, Windsor Regional Hospital, Windsor, Ontario, Canada
Objectives
To evaluate the overall response to first- line TKIs therapy in CML patients
and to examine opportunities for improvement in patients’ outcome.
Imatinib, nilotinib and dasatinib were the first line therapy in 86%, 5% and
2% of CML patients, respectively. Changes from imatinib therapy to other
TKIs and /or bone marrow transplant were seen in 55% of cases. Optimal
responses were seen in 97%, 95%, 86% and 67% at 3, 6, 12 and 18 months
on TKIs therapy, respectively. Overall survival was 92% at 5 years and 86% at
7 years, 75% of overall deaths occurred due to other co morbidities. Optimal
responses if alive at 5 years were, 94%, 90%, 90% and 63% at 3, 6, 12 and
18 months, respectively, and at 7 years were 90%, 83%, 83% and 50% for
same corresponding times. At 6 months 50% of suboptimal responders and
100% of the optimal responders were alive at 7 years.
Conclusion
High rates of optimal responses to TKIs therapy were reported at 3,
6 and 12 months. High survival rates were achieved at 5 and 7 years
and most of the mortalities were related to other co morbidities. The
18 months outcome did not predict the overall survival, while 3 and 6
months outcomes appear to predict survival at 7 years supporting the
new 2013 ELN guidelines.
51. ENHANCING HEALTHCARE PROFESSIONALS
AWARENESS AND UNDERSTANDING OF PSYCHOSOCIAL
DISTRESS AMONG SPOUSAL CAREGIVERS OF
HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: A
ROLE FOR DIGITAL STORIES AND ILLNESS NARRATIVES
Background:
Building on earlier research undertaken by BS, DM and SC, an innovative
approach to knowledge sharing was developed to enhance psychosocial
support for spousal caregivers of hematopoietic stem cell transplant
recipients. The use of digital stories and illness narratives provide
important insight into the meaning of phenomena such as caregiving.
With greater emphasis on patient/family or relationship-centered
care delivery, approaches to education that enhance awareness,
empathy and the meaning of existentially important experiences
become imperative. From a pedagogical perspective, stories can make
challenging information coherent, meaningful and easily understood by
situating complex concepts into practice and practical situations. Such
an approach may be transformative by challenging the HCP/student’s
existing world-view (values, beliefs) through self-reflection.
59
Method/Methodology
Three to five HSCT survivors and their spousal caregivers will take part
in a 3-day workshop to be held March 7-9, 2014. Caregivers will create
digital stories of the experience of caring for an HSCT recipient; illness
narratives will be collected from the HSCT survivor. An educational
module and workbook for HCPs/students will be created, implemented
and evaluated.
Results
Highlights from the workshop, educational module and workbook
along with its role as an educational tool will be presented.
Conclusion
Enhancing awareness, knowledge and understanding of the implications
of informal caregiving is a potentially effective approach to: 1) address
the needs of HSCT spouses whose health may be compromised as a
result of their role, 2) reduce the financial costs/burden to the healthcare
system, and 3) introduce HCPs/students to practice development
strategies that better support optimal healthcare delivery for this
underserviced population – spousal caregivers.
Conclusion
Conceptualizing waiting as a liminal space may offer an alternative
perspective to understanding this phenomenon by suggesting that
waiting is a time of transition and/or transformation where individuals
create and recreate the self as they bridge the gulf between their old
world and the new.
53. THE EXPERIENCE OF SEXUALITY IN INDIVIDUALS
WHO HAVE UNDERGONE HEMATOPOIETIC CELL
TRANSPLANTATION
Background
52. EXPLORING THE CONCEPT OF WAITING AMONG
SPOUSAL CAREGIVERS OF HSCT PATIENTS: THE BETWIXT
AND BETWEEN
Autologous and allogeneic hematopoietic cell transplantation (HCT) are
used as treatment for various hematological diseases. The modalities of
therapy that are part of HCT, namely high dose chemotherapy with or
without total body irradiation (TBI), may have a negative impact on an
individual’s sexuality. Research has revealed that altered sexual function
following HCT is common, affecting between 25-80% of patients. The
primary objective of this study was to identify patients’ experience of
sexuality following autologous or allogeneic HCT.
Background:
Methods
Few studies have explored the meaning of waiting within the context
of cancer beyond wait times, watchful waiting, or waiting for relapse.
Even fewer studies have explored the meaning given to the experience
of waiting and its emotional/psychosocial implications despite the fact
that waiting may be considered a universal experience. While a few
studies have focused on this phenomenon as it pertains to patients little
no to research exists on waiting from the spousal caregiver perspective
suggesting a taken-for-granted notion of waiting.
This study utilized a concurrent, mixed qualitative-quantitative design.
Participants completed the Functional Assessment of Chronic Illness
Therapy-BMT (FACT-BMT) as well as underwent semi-structured
interviews.
Results
Results
Eleven individuals participated in the study. The mean age at time of
transplant was 43 years (range: 17-62) and mean number of months
from transplant to time of study participation was 29 (range: 2-86).
Participants scored relatively high on the FACT-BMT (mean 106 [range:
56-134] out of a possible 148), where higher scores indicate better
quality of life. Regarding sexual function, the most common changes
experienced by the participants were: decreased libido (67% of female
participants; 63% of male participants), difficulties with erectile function
(88% of male participants), dyspareunia (67% of female participants),
vaginal dryness (100% of female participants) and not feeling desirable
(33% of female participants; 38% of male participants).
Waiting emerged as one of four key findings from this study. This
theme highlighted both the complexity and multiple interpretations
spouses assign to the experience of caregiving. In a healthcare
system that conceptualizes waiting within the context of linear time,
spouses struggled to make sense of their experience as both linear
Analysis of the qualitative data obtained from the interviews revealed
several themes pertaining to sexuality and HCT including: changes in
sexual function, coping with impaired fertility, the impact of the disease/
treatment on relationships, and the experience of discussing sexuality
with health care providers.
Method
A mixed method exploratory study examined the experience of caregiving
for spouses of hematopoietic stem cell transplant recipients. A narrative
analytic approach grounded in interpretative phenomenology was used
to analyze the interviews of 11 spouses across 4 points in time over
one year.
60
and embodied. I suggest that our understanding of waiting may be
enhanced by conceptualizing the phenomenon as having residency
within liminal space – the betwixt and between.
Conclusions
In this study, all participants reported changes in sexuality following
HCT. Further study is planned with a view to involve a larger cohort
of transplant recipients as well as to include the partners/spouses of
transplant recipients.
54. THE DEVELOPMENT OF AN ADULT BLOOD AND
MARROW TRANSPLANT SURVIVORSHIP CLINIC
Background
With the number of survivors of hematopoietic cell transplantation (HCT)
continuing to rise, questions abound regarding the optimal care of such
individuals. While the risk of relapse may abate over time, survivors
of HCT are faced with an array of additional potential health and
psychosocial challenges. Following the Institute of Medicine’s seminal
report on cancer survivorship in 2005, survivorship programs are being
established in many oncology centres throughout the world.
Methods
In June 2012, we launched the Adult Blood and Marrow Transplant
Survivorship Clinic at our tertiary oncology centre. The clinic model was
developed after review of existing survivorship clinic models in several
prominent oncology centres as well as after consultation with members
of the multidisciplinary team of care providers at our centre. The
survivorship care plan that is utilized in the clinic integrates components
of the published report on the recommended screening and preventive
practices for survivors of HCT.
The purpose of this presentation is to provide an overview of the clinic,
highlighting the planning and development of the clinic as well as
to discuss how the clinic operates, the clinical issues that have been
identified and review some of the successes and challenges that
have been encountered since the clinic’s inception. For this quality
improvement project, the charts of patients who had been seen in the
clinic from June 2012 until October 2013 were examined. Demographic
data and basic clinical data were reviewed retrospectively.
Results
Ninety patients were seen in the clinic between June 2012 and October
2013. All of the patients seen in the clinic had undergone at least one
allogeneic HCT; 3 patients had undergone 2 allogeneic HCTs while 4
patients had undergone prior autologous HCT. The mean age at time
of clinic visit was 49 years (range 23-69) with a mean time of 11 years
since time of transplant (range 2-28). The most common chronic health
issues reported were fatigue, hypertension, type II diabetes mellitus,
hypothyroidism and chronic pain. Two cases of hyperthyroidism were
picked up in the clinic; both patients went on to see endocrinologists
who diagnosed Graves’ disease. Few patients (n=5) had active chronic
graft versus host disease (GVHD); 4 of the 5 cases had been mild and
had involved the oral cavity. One case involved the skin and the patient
was referred back to the transplant physician for further management
of progressive sclerodermatous-type GVHD of the skin.
Many of the patients reported ongoing psychosocial concerns, including
the inability to return to work due to chronic health issues, financial
concerns and relationship distress. Difficulties with sexual function
were common with women reporting diminished libido, vaginal dryness
and dyspareunia and men reporting diminished libido and erectile
dysfunction.
Conclusions
As the population of cancer survivors continues to grow, so too will
the need for effective and timely survivorship care. We present the
preliminary findings from our Adult Blood and Marrow Transplant
Survivorship Clinic. Our clinic continues to evolve as we aim to help
survivors of HCT achieve the best possible quality of life.
61
Westin Nova Scotian Floor Plan
lobby level
ground floor
Service
Elevators
Harbour Suite
A
elements
on hollis
Tradewinds
Harbour Suite
B
Mens
Room
Elevator to
Pool/Fitness Centre
Foyer
Washrooms
Main
Elevators
Ladies Room
Catering & Reservations Offices
Spa
Front Desk / Reception
Seaport
Room
Retail Space
Roy’s Lounge
& Cafe
Business
Centre
Gift Shop
Main Lobby
Transportation
Meeting Space
To VIA Rail
Train Station
Sales Office
Concierge
Dining Facilities
conference level
first floor
Atlantic Ballroom
Boardroom
Service
Elevators
Elevator to
Pool/Fitness Centre
Commonwealth
Ballroom A
Room
Main
Elevators
Ladies Room
Atlantic Foyer
Mens
Room
Commonwealth
Foyer
Commonwealth
Ballroom B
Northumberland
Mezzanine
Lunenburg
Room
Coat Check
Maritime Room
Bedford Room
Fundy Room
Meeting Space
62
thewestinnovascotian.com
902.421.1000
Social Event
Information
1549 Lower Water Street, Halifax, NS
7:00pm onwards
About CBMTG
The Canadian Blood and Marrow Transplant Group (CBMTG) is a national, voluntary, and multi-disciplinary organization providing leadership and
promoting excellence in patient care, research, and education in the field of BMT.
CBMTG’s vision is that Canada will be the best place in the world to have a blood and marrow transplant. Furthermore, the mission of the association
is that the Canadian Blood and Marrow Transplant Group is the voice of experts working in the field of blood and marrow transplant.
The CBMTG’s values are: excellence, innovation, integrity, collaboration and professionalism in care, education and research in blood and marrow
transplant. While the association’s philosophy is: CBMTG believes that every patient has a right of equal access to the highest quality of life saving
care that can be provided by blood and marrow transplant professionals in Canada.
Based on this, our strategic priorities are as follows:
Education
Providing high quality educational programs that advance the practice of blood and marrow transplantation in Canada.
Research
Establish and organize an effective and sustainable research infrastructure for translational and clinical research.
Outreach
Increase the visibility and influence of CBMTG among members and the public.
Financial Capacity
To support, education, research and outreach initiatives through fundraising, partnerships and the establishment of a charitable organization.
CBMTG Membership:
The CBMTG membership is made up of national and international physicians, nurses, laboratory technicians, pharmacists, and coordinators
working in blood and marrow transplant.
For more information, please visit www.CBMTG.org
63
May 12-15, 2015
Le Centre Sheraton
Montreal Hotel
We invite all BMT health care professionals
to attend our conference in Montreal in 2015.
The 2015 conference planning committee, led by Dr. Silvy Lachance and the Montreal BMT team, will
work to create an exciting program that will feature presentations on the latest developments in
BMT patient care and clinical and laboratory research breakthroughs.
The format of the 2015 CBMTG conference will include scientific plenary sessions, keynote
presentations, multidisciplinary and discipline-specific sessions, oral research presentations,
committee and society meetings and corporate satellite symposia.
CBMTG Head Office: 375 West 5th Avenue, Suite 201 Vancouver, BC V5Y 1J6 T: 604-874-4944 F: 604-874-4378
E: [email protected] W: www.cbmtg.org
Annual Conference of the Canadian Blood and Marrow Transplant Group
An educational conference for professionals in the field of Blood and Marrow Transplantation

to view the Scientific Program

Transcription

Similar documents

The Importance of Routine Exercise for Dialysis Patients

Solid Organ Resource Guide v5

The Role of Outcomes Registries in Blood and Marrow

JD release, 8.16 - Gift of Life Donor Program

Hillel — UConn

President`s Message -Robert Golding

COMRADERY FROM COAST-TO

Starting a HSCT Program - front lines perspective

interactive session: management