Understanding BMT - Aplastic Anemia and MDS International

Definitions
• Stem Cell Transplantation (aka BMT)
Understanding BMT: Before, During,
and After Transplant
– The transfer of Hematopoietic Stem Cells from Donor
to Recipient
• What is a Stem Cell?
– Stem cells are defined by two characteristics:
• They can make copies of themselves, or self-renew
• They can differentiate, or develop, into more
specialized cells
(BMT 101)
Corey Cutler, MD MPH FRCP(C)
Associate Professor of Medicine
Harvard Medical School
Dana-Farber Cancer Institute
Boston, MA
Rationale for Transplantation
Definitions
• Are there different types of Stem Cells?
• Elimination AND Replacement of:
– Embryonic / Pluripotent Stem Cells
– Tissue Specific Stem Cells
• Hematopoietic Stem Cells – A stem cell capable of
giving rise to ALL cells in the blood and immune system
– Diseased marrow
– Poorly functioning marrow
– Immune compromised marrow
– Metabolically compromised marrow
• Protection against ultra-high doses of
chemoradiotherapy
• Establish immunologic platform for
immunotherapy
Types of Transplantation
Indications for Transplantation
Autologous
• Autologous
– High doses of chemotherapy and/or radiation
– Designed to kill tumor; overcome resistance with dose
intensity
– Requires stem cell rescue
– Not really a transplant
4
– Multiple Myeloma in remission
• Prolongation of remission
–
–
–
–
–
Allogeneic
– 2 mechanisms to cure:
• Immunologic: Donor vs. Host (Graft vs. Tumor)
• Chemotherapy and/or radiation
Decision to use autologous/allogeneic marrow
source is disease, stage and patient specific
5
Diffuse Large B Cell NHL in 2nd remission
Hodgkin Disease in remission
Mantle Cell NHL
Some Germ Cell Tumors
AML, in very rare circumstances
Curative Intent
Indications for Transplantation Allogeneic
Stem Cell Transplant Decision Tree
Type of Transplant
Autologous
Allogeneic
Conditioning
Intensity
• High (Myeloablative)
Related Donor (Total N=3,282)
Number of Transplants
2,500
Unrelated Donor (Total N=3,389)
• High (Myeloablative)
• Reduced Intensity
2,000
1,500
1,000
500
0
AML
ALL
MDS/
MPD
NHL
Aplastic CML Multiple HD
Anemia
Myeloma
Other Other NonLeuk Cancer Malig
Disease
8
What is Better? Myeloablative or RIC?
Conditioning Regimen
• Determined by:
CIBMTR, Age >50, 1998–2006
Primary tumor type
Stage of disease at transplantation
Graft vs. tumor effect in that disease
Performance status/comorbidity of recipient
100
Probability of Survival
–
–
–
–
• Large variety of regimens exist
• Differ in intensity and toxicity
– Ablative is Hard; RIC is pretty easy
100
90
90
80
80
70
70
60
60
50
50
Reduced-intensity conditioning, HLA-identical sibling
(N=232)
40
40
30
30
Myeloablative, HLA-identical sibling (N=318)
20
20
10
• We have “Recipes” for these regimens
0
0
9
BMT CTN 0901
10
0
1
2
3
4
5
6
Years
Overall Survival by Treatment Arm
Advanced MDS /
AML< 5% blasts
Randomize
RIC regimens
Bu/Flu
Flu/Mel
GVHD
Prophylaxis per
Institutional
practice
Centers will choose one
myeloablative and one
reduced intensity
regimen for each patient
at time of randomization
RIC 67.7%
P=0.07 (18 month pointwise)
9.7% difference (95% CI: -0.9%, 20.3%) MAC vs. RIC
MAC Regimens
Bu/Flu
Bu/Cy
Cy/TBI
18 Month Overall Survival
12
Stem Cell Transplant Decision Tree
Overall Survival by Disease Group
Survival Probability
Survival Probability
RIC 85.2%
RIC 63%
Type of Transplant
Autologous
Conditioning
Intensity
• High (Myeloablative)
• High (Myeloablative)
• Reduced Intensity
Donor Type
• Self
• Related
• Unrelated
• Perfect
• Matched
• Mismatched
• Highly Mismatched
Degree of Match
Months
MAC 27
RIC 27
25
26
25
26
23
25
Months
22
23
22
22
21
20
108
110
105
103
101
91
91
77
87
73
77
67
68
62
Allogeneic
13
Finding a Donor
14
The HLA System
• Goal is to MATCH donor-recipient pairs
– Not a problem in Autologous transplantation
– Identical Twins (Syngeneic Transplantation) not
commonly found nor used
• Matching performed for HLA (Human Leukocyte
Antigen) molecules, encoded by MHC complex
(Major Histocompatibility Complex)
• Matching at non-HLA loci also important, but not
done (yet).
Klein and Sato, NEJM 2000
Histocompatibility
Histocompatibility – Unrelated Donors
HLA-A -B -C
-DR -DP -DQ
2132 2798 1672 1196 179 158
HLA-A -B -C
-DR -DP -DQ
2132 2798 1672 1196 179 158
Nearly Infinite Possible Combinations!!!
“Perfect” Match Rates in the Adult
Donor Registry
“Perfect” and “Pretty Good” Match
Rates in the Adult Donor Registry
19
20
Courtesy Martin Maiers, NMDP Bioinformatics
Courtesy Martin Maiers, NMDP Bioinformatics
Stem Cell Transplant Decision Tree
Does the Degree of Match Matter?
Weisdorf, BBMT 2008
Bone Marrow
Peripheral Blood
Stem Cells
Umbilical Cord
Blood
Hard
Easy
Very Easy
18-21 days
12-15 days
21-40 days
Immune
Reconstitution
Good
Better
Very Poor
GVHD Rates
Average
Perhaps Higher
Low
Graft-vs.Tumor
Average
Perhaps Higher
??
Engraftment
Autologous
Allogeneic
Conditioning
Intensity
• High (Myeloablative)
• High (Myeloablative)
• Reduced Intensity
Donor Type
• Self
• Related
• Unrelated
Degree of Match
• Perfect
• Matched
• Mismatched
• Highly Mismatched
Stem Cell Source
• Bone Marrow
• PBSC
• Bone Marrow
• PBSC
• Umbilical Cord Blood
22
Umbilical Cord Blood – A New Alternative
Stem Cell Source
Ease of Collection
Type of Transplant
• Medical waste – Procured at the time of delivery
• Contains hematopoietic stem cells – Can be
used for transplantation
• Immunologically “immature” – Can be used with
less stringent matching
“Perfect”, “Pretty Good” and UCB Match
Rates in the Adult Donor Registry
Haploidentical Transplantation
AB
E F
AD
CD
X
BC
BD
NIPA mm
AF
AE
AC
NIMA mm
DF
25
Courtesy Martin Maiers, NMDP Bioinformatics
Preparing for Transplantation
27
Preparing for Transplantation
28
• Pre-Transplant Testing
–
–
–
–
Blood tests: Kidney, Liver function, Infectious disease
Functional tests: Heart, Lung
Psychosocial interviews
Financials
• Pre-Transplant Teaching
• Consent Session
– Should be VERY thorough
– At least an hour
– Ask a lot of questions
– Be prepared to be offered participation in Research
studies
– Restrictions / Safety
– Nutrition
– Medication
Other Things To Do Pre-Transplant
Grand Overview of Transplantation
29
•
•
•
•
Go see a bunch of movies
Go out to eat
Gain some weight
Have a party
Conditioning
Transplantation
Engraftment
Recovery
Complications
30
Transplantation Timeline
Post-Transplantation
Discharge
Recovery
GVHD
Infection
Admission
Transplantation
Line Placement
• A lot of ‘alone’ time
– Designed to PROTECT you
• Frequent visits to the clinic (big social outing of
the week)
-7
-1
0
10-18
Conditioning
Await Engraftment
Chemotherapy, Radiation
Infection
Mucositis
Bad Complications
• Lots of medications
• Complication time
• You won’t feel great. Yet.
GVHD
GVHD - Background
• After disease relapse, GVHD is the most
common cause of treatment failure after
transplantation.
• 2 syndromes:
– Acute GVHD
– Chronic GVHD
• Caused by the interaction between the
transplanted immune system (Graft) and recipient
tissues (Host)
Rejection
Transplanted Organ
• Previously defined by temporal relationship to time of
transplantation
• Now defined by clinical features
• Differences in pathobiology
Immune System
GVHD
Transplanted Organ
Target Tissues
Double-Edged Sword
Double-Edged Sword
Graft-vs.-Leukemia
Twins (N=70)
0.6
T Cell Depletion (N=401)
0.4
No GVHD (N=433)
Acute GVHD only (N=738)
0.2
Chronic GVHD only (N=127)
0.0
0
12
24 30
48
MONTHS
60
72
Both Acute and Chronic GVHD
(N=485)
INCREASE
FOLD DECREASE OR INCREASE IN RISK
0.8
TREATMENT
FAILURE
RELAPSE
4
P=.0001
3
2
1
P=.04
GVHD Grade
*
P=.02P=.009 P=.04
*
P=.02
III IV
I II III IV I II
2
DECREASE
PROBABILITY OF RELAPSE
5
1.0
GVHD Grade
3
4
5
Horowitz et al, Blood 1990
Horowitz et al, Blood 1990
Acute GVHD
Incidence:
– 35% after Related Donor Transplantation
– 50% after Unrelated Donor Transplantation
Despite prophylaxis
Risk Factors
for ↑Acute
GVHD
Condition That
Risk of Acute
GVHD
Factor
Donor-Recipient Factors
Major HLA Disparity (HLA Class I, II)
HLA Mismatched donor > Matched Donor
Minor HLA Disparity (mHA)
Unrelated Donor > Related Donor
Sex Matching
Mismatch > Match
Donor Parity
Multiparity > Nulliparity
Donor Age
Older donor > Younger Donor
ABO type
ABO Mismatch > ABO Match
Donor CMV Serostatus
CMV positive > CMV Negative
Cytokine Gene Polymorphisms
Numerous Associated with Acute GVHD
Stem Cell Graft Factors
– Current Standard: Tacrolimus/Cyclosporine and
Methotrexate
Stem Cell Source
PBSC > BM > UCB
Graft composition
Higher CD34+ count > Lower CD34+ cell count*
Higher T cell dose > Lower T cell dose*
Transplantation Factors
Conditioning Intensity
Myeloablative > Reduced-intensity Regimens
Infection
Acute GVHD
• Clinicopathologic syndrome
– Skin
Erythematous rash  Bullae  Desquamation
– Liver
Hyperbilirubinemia  Hepatic failure
– Gut
Host
Defense
Deficit
Neutropenia
Acute GVHD + Rx
Bacterial
Gram Negative Rods
Chronic GVHD + Rx
Mucositis
Central Venous Catheters
Encapsulated Bacteria/Listeria/Salmonella/Nocardia
Gram Positive Cocci
Aspergillus
Fungal
Aspergillus/Vasculotrophic Molds
Candida sp
Secretory diarrhea  Ileus
Pneumocystis jirovecii pneumonia
Respiratory and Enteric viruses - Epidemic
Viral
CMV
CMV
BK Virus
HHV 6
HSV / Resistant HSV
0
Marrow infusion
Engraftment
VZV
100
50
365
days
Days after allogeneic HSCT
Low Risk
Prophylaxis/preemptive/empiric
Post-Transplantation – Beyond 100 Days
• 2 Main issues
– Middle Term Complications
– Late Effects and Survivorship
Chronic GVHD - Background
• >50% of Related and Unrelated Recipients
– Incidence increasing as early transplant outcomes
improve
• Important cause of morbidity in the later posttransplant period
– Most have more than 1 organ system involved
• Median 2-3 years of treatment
• Associated with Quality of Life and functional
deficits
High Risk
SYSTEM
Organ Involvement
Chronic GVHD – Organ Involvement
SIGNS
SYMPTOMS
SKIN AND RELATED
STRUCTURES
Skin: Hyper/hypopigmentation,
lichenoid, sclerodermal,
papulosquamous, ichthyosiform and
psoriasiform changes. Atrophy,
poikiloderma and ulcers. Nails:
dystrophy, longitudinal ridging,
onycholysis, pterygium, destruction.
Scalp: scaling, fibrosis, scarring and
non-scarring alopecia, papulosquamous
changes.
Pruritus, dryness, pain,
infection, rigidity,
decreased range of motion,
photosensitivity.
Nail and hair loss.
MOUTH
Lichenoid changes, erythema, ulcers,
xerostomia, fibrosis, leukoplakia. Dental
caries.
Pain, odinophagia,
dysphagia, dysgeusia,
dryness, sensitivity to food.
EYES
Keratoconjunctivis sicca, corneal
ulcerations.
Pain, dryness photophobia.
MUSCULOSKELETAL
Polymyositis, muscle weakness,
myalgias, arthritis, arthralgias, fasciitis.
Weakness, arthralgias,
myalgias, decrease ROM
GI TRACT
Upper: Abnormal motility, esophageal
fibrosis, ulcerations, strictures.
Lower: Mucosal
abnormalities/malabsorption,
submucosal fibrosis
Odynophagia and lower
dysphagia, pain, heartburn,
nausea, anorexia, vomiting,
abdominal pain,
diarrhea/malabsorption,
dehydration, weight loss
1
0.9
IBMTR-1 IBMTR-2 NMDP
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Cutaneous
Oral
Liver
Eye
Wt loss
Diarrhea
Lung
Esophagus Joint
Adapted from Lee et al, 2002
SYSTEM
SIGNS
SYMPTOMS
LIVER
Hyperbilirrubinemia, elevated Alk P,
elevated ALT/AST, fibrosis.
Fatigue, jaundice, pruritus.
LUNG
Obstructive (BO/BOOP) or restrictive
(scleroderma of the chest) dysfunction.
Air trapping, bronchiectasis,
pneumothorax, pneumomediastinum,
subcutaneous emphysema. Microbial
colonization or pneumonia.
Dyspnea, wheezing, productive or
non productive cough.
NEUROLOGIC
Neuropathy, myasthenic syndromes.
Pain, burning, dysesthesias,
paresthesias, muscle weakness
VAGINAL
MUCOSA
Erythema, lichenoid changes, dryness,
ulcers, strictures/stenosis.
Pain, burning, dryness,
Dyspareunia
SEROSAL
Serositis, pericardial, pleural and
peritoneal effusions.
Dyspnea, chest pain, pleuritic
pain, abdominal pain, ascites.
HEMATOPOIETIC
Isolated or combined cytopenias,
eosinophilia, hemolysis.
Fatigue, fever, infection, bleeding.
IMMUNOLOGIC
Repeated infections of various
etiologies, lymphopenia,
Hyper/hypogammaglobulinemia
Increased susceptibility to
infection.
Treatment Strategy
• Local Symptoms  Local Rx
– Early identification crucial
– Supportive vs. Local immunosuppressive
Treatment Strategy
• Systemic Symptoms / Multiple Local Sites  Systemic Rx
• Initial Rx:
– Prednisone 1 mg/kg/day
– Tacrolimus: 5-10 ng/ml or
– Cyclosporine: 200-400 µg/L
• Complete Response Rate: 50-55%
• Median Time to Discontinue Immune Therapy:
1.6 – 2.2 years!!
• Multiple Clinical Trials available – You should participate!!!
– www.clinicaltrials.gov
– National Institutes of Health Consensus
Development Project on Criteria for Clinical Trials
inChronic Graft-versus-Host Disease: The 2014
Ancillary Therapy and Supportive Care Working
Group Report.
Biology of Blood and Marrow Transplantation, 2015
• Can be accessed through ASBMT Website:
http://www.asbmt.org/?page=GuidelineStatements
Post-Transplant Transitions
• You will experience a number of transitions post
transplant
– Gaining more independence and freedom - welcomed yet
very stressful
– Relationships with family/friends/loved ones-going through a
time of adjustment
– Financial pressures – Going/not going back to work
• Acknowledge the enormity of your experience
–
–
–
–
The reality of your diagnosis
The trauma inherent in transplant
The loss of who you were and the security you previously felt
Seek help if you are stuck
Psychosocial Effects of BMT
Changing Emotions
•
•
BMT survivors generally experience a high global quality of life
Some problems may be persistent
•
Emotional or psychological distress can be common
•
Depression
– Low energy, sleep problems
–
–
–
–
• Recovery is a slow process
• Emotions some experience after transplant:
– Frustration: Lack of energy to do what you once did
– Anger: Why do I have GVHD? Why can't I just feel
normal?
– Guilt: Being a burden to caregiver/family/loved ones
– Mood Changes: "up and down"--caused by
medications (steroids)
– Depression/Anxiety
Frequently observed
Exact prevalence rates unknown
Depression before and after transplant can affect morbidity and mortality
Treatment is important
– Women more likely to have current depression (75% v 25%, p=.007)
– Women more likely to receive antidepressants (92% v 50%, p=.02)
– People with treated depression are similar to those without depression
DeMarinis et al., European J of Cancer Care
Quality of Life
Cognitive Changes
• Fatigue: Patients give up being as they were
• Work: full-time, part-time, permanent disability
• Recreation: This can change too. Figure out
what you CAN do.
• Relationships: Transplant can take a toll
Physical
• Chronic Graft vs. Host Disease
Spiritual
Social
•
Clinical evaluation for neurologic dysfunction is warranted
• Neuropsychological testing
• Additional tests may be indicated
•
What we know
– Pre HSCT deficits are common
– Post HSCT deficits are even more common
•
Complication rates
•
Types of complications
– Late CNS infections
– Cerebrovascular complications
– 20% will report impaired memory, attention span, verbal fluency
– Allogeneic (Unrelated > Related) >> Autologous
Psychological
Sexuality after Transplant
•
•
•
•
•
Important QoL issue
Sexual dysfunction is a common, enduring consequence of
systemic cancer treatment
Changes in body image, decline in perceived attractiveness
Infertility for both men and women
Majority of survivors say they were not prepared for changes in
sex life
Coping Strategies
• Recognize the impact has been physical, emotional,
psychological and spiritual
• Go at your OWN pace, not an 'expected' pace
• Your situation, coping style may be different from others
- that's OK!
– Women: Ovarian failure  low estrogen levels and vaginal GVHD 
stenosis, mucosal changes  pain, irritation and sensitivity
– By 2 yrs, there is improvement compared to 6 months, but quantity and
quality still not what it was even 5 yrs later
• Be open, be honest about your feelings and needs
– Men: Gonadal and cavernosal insufficiency  ED and lower libido
– Rates of sexual activity improve by 1 year, but takes 2 years to see
improvement in quality and quantity. At 5 years still lower function
compared to no BMT group
• Ask what would be most helpful to me now?
• Try to process what you are experiencing with a loved
one or a professional
– Support group
– One on one counseling
– Reading
Taking care of yourself
•
•
•
•
•
•
•
•
Take your medications
Make your appointments
Respect your altered immune function
Mind your emotional well being
Get enough sleep
Pay attention, keep lists, make associations
Consider cognitive rehabilitation services
Keep your perspective
– Do not over-generalize
– Time heals all?
• Nutrition
• Exercise
Post-Transplant Diet
• Eat 5-10 servings fruits & veggies each day
– 1 serving = 1/2 cup cut, cooked or sliced; 1 piece
medium fruit; 1 cup leafy greens
• Re-shape your plate
– 1/2 veggies, 1/4 protein, 1/4 whole grains
• Emphasis on variety
• Look for richly colored plant foods
• Emphasize whole grains
– Reduce risk for certain cancers, diabetes and heart
disease
– Keep weight off
– Lower cholesterol levels
– Promote digestive health
• Reduce consumption of saturated and trans- fats, increase
monounsaturated and omega-3 Fats
Returning to Work
•
Up to 89% of BMT patients return to work or school within 5 years
after treatment.
•
Influences that impact the ability to return to work are:
•
–
–
–
–
–
Influences that impact the INability to return to work:
–
–
–
–
–
•
Age
Gender
Education
Personal values
Perceived advantages of work
Physical demands
Job Lock
Employer accommodation
Fear of disclosure
Perceived discrimination
Data suggests BONE MARROW recipients more likely to return
to work than PBSC recipients (Lee, ASH 2015)
Dietary Challenges after Transplant
• Weight gain or loss
• Appetite changes
–
–
–
–
–
Small, frequent meals
Avoid eating snacks too close to meal times
Choose nutrient dense foods
Fortify foods to boost calories
Try new recipes
• Lack of interest in food
• Taste alterations / Dry Mouth
–
–
–
–
Drink plenty of fluids, at least 8 cups per day
Moisten foods with gravies, sauces, or broth
Limit caffeine
Artificial saliva products
• Steroids, GVHD
Focus on Physical Activity
Physical Activity + Proper Diet = Healthy Weight
• Create an individualized fitness plan
– Always talk with your doctor first
– Schedule time for activity each day, remember every
bit counts
– Ensure intensity appropriate
– Choose activities you enjoy
– Find a workout “buddy”
• Incorporate key components
– Cardiovascular exercise, strength, flexibility and
relaxation
Employer Accommodation
Accommodation: Aiding an employee to perform
their job by providing modifications.
“Reasonable” accommodations
–
–
–
–
–
–
Change in duties
Change in work hours
Flexible work hours
Periodic rest breaks
Allow employees to work from home
Modify dress code
Caregivers
Survivorship in BMT
•
Acknowledge the long haul of BMT caregiving
– Physical demands
– Feelings of loss, anger, fatigue, resentment, hope
•
Change has been difficult, you have HAD to adapt to the changeshift in roles
•
Sometimes paddling in the same direction as your loved one is
difficult
•
Every relationship/family functions differently
•
•
As a caregiver, must adapt to what works best for you
Make time for yourself
•
Rely upon others (transportation, child care, meals)
•
Say NO to non-essential needs – Prioritize!
After 1998
• 2 components:
– Surviving Malignancy
– Surviving Transplantation
Donor-recipient matching
GVHD prophylaxis anfd treatment
Supportive care
Majhail et al. Recommended screening and
preventive practices for long-term survivors after
hematopoietic cell transplantation.
Biology of Blood and Marrow Transplantation, 2012
• Different sets of risks and complications need
to be considered
Medical Monitoring
Antin JH. Long term care after hematopoietic –cell
transplantation in adults.
New England Journal of Medicine, 2002
Medical Monitoring
Organ
Risk
Outcome
What To Do?
Mouth
Radiation, cGVHD
Dryness, Caries
Regular dental exams
Monitor for oral cancers
Eyes
Radiation, cGVHD,
steroids
Dryness, Cataracts
Regular eye exams
Schirmer test for dryness
Bones
Radiation, steroids, Osteoporosis, fracture
low estrogen/testost.
Radiation, Immune
suppression
Endocrine Radiation, Chemo,
steroids
•
•
•
Medical Monitoring after BMT
Survivorship in BMT
Lungs
Before 1998
Outcome
Risk
What To Do?
Infection
cGVHD, Immune Suppression
Prophylaxis
Second Cancers
Radiation, Chemotherapy,
cGVHD, Immune Suppression
Screening exams
Bone Densitometry
Calcium/Vitamin D
Hormone replacement
Cardiovascular
Steroids, Hypogonadal state,
Medications, Glucose
Intolerance
Routine BP monitoring
Routine Glucose monitory
Pneumonitis
Quit smoking
Regular lung function test
General Health
Survivorship
See your PCP !
Hypothyroidism
Hypoadrenalism
Hypogonadism
Screening
Slow steroid tapers
Hormone replacement
Allogeneic BMT Survivorship Clinic
• Target population
– Allogeneic recipients of high-dose myeloablative
conditioning
– Alive, without malignancy, 12 months after
transplantation
– May have evidence of chronic GVHD
– Total treatment considered
•
•
•
•
Chemotherapy to treat malignancy
Focal radiotherapy to treat malignancy
High-dose chemotherapy for transplant prep
Total body irradiation for transplant prep
Allogeneic BMT Survivorship Clinic
• Providers
– BMT Specialists: MD and NP – Endocrine,
cardiovascular, respiratory, bone, sexuality, cancer
screening
– Dermatology
– Oral Medicine
– Ophthalmology
– Exercise Physiology
– Nutrition
– Psychosocial Counselor
Allogeneic BMT Survivorship Clinic
• Multidisciplinary clinic
– 1x/month, capture all patients (voluntary) for a one
time consultative visit
• Goals of the clinic
– Develop wellness plan to address the needs of this
high risk group
– Develop an individualized follow up plan to address
the non-GVHD related risks of transplant survivors
Treatment summary
 Diagnostic tests performed and results
 Tumor characteristics (e.g. site, stage, grade, markers)
 Dates of treatment initiation and completion
 Surgery, radiotherapy, chemotherapy, including agents used
 Treatment regimen, total dosage, clinical trials (if any),
and toxicities experienced during treatment
 Psychosocial, nutritional, and other supportive services
 Contact information on treating institutions and providers
 Identification of a key coordinator of continuing care
• Patients will be followed annually by NP for their
survivorship needs, outlined in the wellness plan
• Research Agenda
More Resources in BMT
• National Marrow Donor Program
• Questions?
– www.bethematch.org
– Smartphone app (excellent)
• BMT InfoNet
– www.bmtinfonet.org
• nbmtLink
– www.nbmtlink.org
72
HSCT Outcomes - MDS
2001-2011
Transplant for MDS and AA
Timing of HCT for MDS
Summary of Decision Models
When?
Not too early, but not too late
Probably no single formula to fit all patients
Figure 1
Markov Models useful since there is NO randomized
data
Myeloablative, Sibling
Donor Cutler 2004
Low Risk IPSS
Int-1 Risk IPSS
Int-2 Risk IPSS
High Risk IPSS
MDS
RIC
Transplantation
Non-transplant
Therapies
Alive Post
Transplantation
Alive
RIC, Sibling or Matched, Unrelated Donor
Koreth 2013
RIC or Ablative, Sibling or Matched, Unrelated
Donor Allesandrino 2013
p < 0.001
Dead
Transplant
Non-Transplant
Age and Comorbidity
Donor Availability
Relative Risk (95% CI):
8/8 MUD vs. Sib
7/8 MUD vs. Sib
7/8 MUD vs. 8/8 MUD
100
Probability of Survival, %
90
100
1.12 (0.89-1.39)
1.43 (1.08-1.91)
1.29 (1.00-1.65)
90
80
80
70
70
60
60
Sib (N=176)
50
50
40
40
30
30
7/8 MUD (N=112)
20
20
8/8 MUD (N=413)
10
10
0
0
0
6
12
18
24
30
36
Months
McClune et al, J Clin Onc 2009
Sorror et al, J Clin Onc 2014
Saber et al, Blood 2013
Donor Availability
HSCT Outcomes - SAA
2001-2011
1994-1999
100
100
Probability, %
80
60
80
>20 y, Sibling Donor (N = 844)
60
> 20y, Sibling Donor (N = 845)
40
< 20 y, Unrelated Donor, (N = 244)
20
>20 y, Unrelated Donor, (N = 114)
Partially-matched UD (N=289)
Cord Blood (N=153)
40
20
Mismatched UD (N=65)
Haploidentical donor (N=95)
Log Rank p-value = 0.24
0
0
1
2
0
3
4
5
6
7
8
9
Years
Courtesy W. Saber
HCT for SAA
• This is an HCT EMERGENCY
• HLA type IMMEDIATELY
– Serologic family typing available often in 1-2 business
days
• Avoid Transfusion if possible
– Permissive anemia
– Permissive thrombocytopenia
Doney, Ann Intern Med 1997