Geisinger Researchers Investigate Cluster of Rare Blood Cancer in Hazleton

RCesearch
onnections
Linking the Research Community
May 2010
Geisinger Researchers Investigate Cluster of
Rare Blood Cancer in Hazleton
A rare form of blood cancer appears to
occur more often in residents of Carbon,
Luzerne, and Schuylkill counties than
in residents of other Pennsylvania
counties. Thanks to the efforts of Sen.
Arlen Specter and the Centers for
Disease Control and Prevention (CDC),
Geisinger physicians and investigators
have initiated a coordinated series
of projects to scientifically study the
disease and its occurrence in our patient
population.
Polycythemia vera (P. vera) is a
myeloproliferative disorder (MPD)
characterized by both an abnormal
increase in red blood cells and a specific
mutation in JAK2V617F (JAK2), a
gene that signals blood cells to grow.
Paul Roda, MD, FACP, a hematologist/
oncologist at Geisinger - Hazleton
Cancer Center in northeast Pennsylvania,
is principal investigator for a series of
four interrelated projects investigating
P. vera and its increased prevalence in
Pennsylvania’s coal region. The four
projects are funded by the CDC.
“Harsh Gandhi, MD, (Medical
Oncology), Jose Castillo, MD,
(Hematology/Oncology) and I recognized
that P. vera seemed more common in the
Hazleton area,” Dr. Roda said, “but we
never had sufficient resources available
to begin to adequately address this issue.
With expert geneticists at the Weis
Center and genetic epidemiologists at the
Henry Hood Center for Health Research
working with us, we will hopefully be able
to understand the extent of the disease in
continued on page 2
Geisinger Joins National Research Consortium
Geisinger has recently joined the
Myeloproliferative Disorders Research
Consortium (MPD-RC). MPD-RC
investigators hail from approximately
28 institutions throughout the U.S.
and Europe and share a commitment to
enhancing research on MPDs, realizing
that clinical and basic research in this
area cannot flourish in isolation.
Funded by the National Cancer Institute
and the Centers of Disease Control,
the MPD-RC’s mission is to achieve an
understanding of these disorders and to
develop curative strategies. As a MPDRC member, Geisinger researchers
have the opportunity to participate in
Consortium studies to investigate new
treatment modalities as well as access to
the MPD-RC Research Tissue Bank for
laboratory studies.
Through the MPD-RC, three studies are
also opening for accrual:
1. A multicenter, Phase I/II study of
Lestaurtinib in adults with myelofibrosis
(led by Dr. Syed Karim);
2. An international, Phase II study to
estimate the difference in reduction of
leukocyte activation in high-risk MPD
patients randomized to clopidogrel
continued on page 3
System Stages Multi-Prong
Attack on Cancer
By T. Ravikumar, M.D.
Geisinger’s Cancer Program strives
to provide
personalized
cancer care of
unrivalled quality
to the citizens of
central and NE
Pennsylvania. Our
long-term mission
is to reduce the
cancer burden of the communities
we serve.
Our care delivery model is
multidisciplinary (multidisciplinary
clinics) and is comprised of 10 teams
of specialists, each focusing on specific
anatomic sites/diseases (“tumor study
groups”). The leukemia/lymphoma/
myeloproliferative neoplasm program
represents one such team nonpareil.
Stemming from astute observations
of Paul Roda, M.D., and his
colleagues that P. vera is more
continued on page 3
Clarifying Terminology
Myeloproliferative disorders (MPDs),
also known as myeloproliferative
neoplasms (MPNs), are a group of
bone marrow cancers that eventually
overgrow the normal marrow and
include chronic myelogenous
leukemia, P. vera, essential
thrombocythemia and primary
myelofibrosis.
Studies to Look at Possibility of Environmental Role in P. Vera Cluster
Although current studies are not
designed to answer questions about an
environmental role, they may open the
door for further studies that would look
at the environment as a contributing
factor. Tamaqua, Hazelton and
surrounding areas are known for many
sources of hazardous material, including
waste-coal power plants and the U.S.
Environmental Protection Agency
Superfund sites – those identified by the
government for toxic waste clean-up.
In a recent publication, Use of Molecular
Testing to Identify a Cluster of Patients
with Polycythemia Vera in Eastern
Pennsylvania (Seaman V, Jumaan A,
Yanni E et al. ATSDR, CDC. 2009,
Cancer Biomarker PREV 2009: 18 (2).
Feb 2009) molecular tools were used to
estimate the occurrence of P. vera in the
region.
To better understand whether there really
is a higher incidence of P. vera in this
area, the JAK2 Prevalence Study (Glenn
Gerhard, MD principal investigator and
David Carey, PhD, co-investigator) will
evaluate the prevalance of an acquired
mutation.
This three-year study funded by
the CDC (September 2009 through
September 2012) to evaluate the
prevalence of an acquired mutation
(referred to as JAK2V617F) that is
associated with P. vera. JAK2V617F will
be measured in “healthy” individuals
(those not currently diagnosed with
an MPN) in Pennsylvania’s tri-county
coal region, as well as in patients from
other counties with lower rates of P.
vera. Approximately 6,000 Geisinger
patients will be studied using samples
from the Geisinger MyCode Project,
a biorepository of blood and DNA
samples. Samples and data from the two
groups will be compared to determine if
there is a higher rate of JAK2V617F in
the coal region. It will be important to
determine if these individuals have MPN
symptoms and, if not, to follow them to
see if the disease appears years later.
Genetic studies suggest that a relatively
common variant in the JAK2 gene
predisposes susceptible individuals
to the JAK2V617F mutation and an
MPN. As part of this research study, the
frequency of this genetic variant will
also be determined and compared to the
occurrence of JAK2V617F in regional
populations.
“Given this known cluster of disease
prevalence in our community and
Geisinger’s substantial support in
establishing a fully integrated electronic
health record and a data repository to
link patients to genetic predisposition,”
notes Gerhard, “a unique opportunity
exists to make seminal findings in the
possible link between environment and
disease and influence future research and
clinical applications.”
Geisinger Researchers Investigate Cluster of Rare Blood Cancer in Hazleton
continued from page 1
the Hazelton area and to learn more about
the disease and possible treatments.”
Experts believe the environment may
be a contributing factor. Hazelton and
surrounding areas have numerous sources
of hazardous material, including wastecoal power plants and U.S. Environmental
Protection Agency Superfund sites
earmarked for toxic waste cleanup. The
P. vera studies may shed light on the
environment’s role and help delineate
future studies. Dr. Roda is personally
motivated because the disease cluster is
“literally outside the door of the GeisingerHazleton Cancer Center,” where he has
practiced for more than 30 years.
The three CDC-funded research projects
are:
1. Patterns of Diagnosis and Reporting,
undertaken by Dr. Roda and Geisinger
Henry Hood Center for Health Research
researcher Porat Erlich, PhD, involves
reviewing patient charts to determine if
physicians are using the readily available
genetic test for JAK2 and identifying
specific barriers to its use.
2. The Natural History of P. vera,
conducted by Dr. Roda, will help
characterize the latency and progression
of the disease and its symptoms by
following carriers of the JAK2 mutation
who have participated in a CDCsponsored screening program.
3. JAK2 Prevalence, conducted by David
Carey, PhD, and Glenn Gerhard, MD,
will use molecular diagnostic tools and
RESEARCH CONNECTIONS
-2-
Geisinger’s MyCode program to identify
the prevalence of the JAK2 mutation
in a sample Hazleton cohort as well as
in a similar population from a different
geographic area.
CDC funding is also supporting physician
education that revolves around increasing
primary care physicians’ knowledge of P.
vera and appropriate patient screening for
the disorder, and collaborations between
hematologists/oncologists, epidemiologists,
basic science researchers, statisticians, etc.
to determine any link between the disorder
and the environment.
A Community Action Committee
provides area residents an opportunity
to play an integral role in addressing this
disease’s risk to their community.
In Search of Answers
Cancer Specialist/Researcher Paul Roda, MD, Explores Apparent Cancer Cluster
Geisinger cancer
specialist Paul Roda,
MD, FACP, wasn’t
satisfied treating
patient after patient
for a blood cancer
with a mysteriously
similar etiology.
Paul Roda, M.D.
“After observing for
years the high incidence of P.vera in our
region, I felt I needed to do more than
orchestrate the treatment – I wanted to
be part of orchestrating the solution,”
says Dr. Roda.
Dr. Roda is now principal investigator
on the P.vera study, working with
the Centers for Disease Control and
Prevention (CDC) (see lead story).
“It is intellectually challenging to be on
the research end of a disease. I enjoy
being able to take a day a week out of
my practice to work with experts in the
field to answer important questions about
P.vera,” he adds.
Attracted by the ability to participate in
clinical trials, Dr. Roda and his practice
colleagues Jose Castillo, MD, and Harsh
Gandhi, MD, joined Geisinger in 2007.
Dr. Roda says Geisinger’s advanced
and extensive electronic record has
been valuable to his investigation into
the pattern of P.vera in northeastern
Pennsylvania.
“Today, patients have greater
expectations about what the medical
field can do for them,” he notes. “When I
first started my practice, patients viewed
cancer as an incurable disease, now they
see it as more of a common cold —
something that should always be curable.
As physicians, we walk a tightrope
between hope and reality.”
Dr. Roda has been at his Hazleton location
for 28 years. A graduate of the Hahnemann
University School of Medicine, Dr. Roda
completed a residency at the Medical
College of Pennsylvania and a fellowship
at Hahnemann University Hospital.
Board-certified in medical oncology and
internal medicine, Dr. Roda specializes in
hematology and oncology.
Geisinger Joins National Research Consortium
continued from page 1
(and aspirin + hydroxyurea) compared
to patients randomized to placebo (and
aspirin + hydroxyurea);
3. An assessment of the safety for
patients treated with the combination
therapy and an estimate of the
prevalence of clopidogrel resistance in
high-risk P. vera patients.
Dr. Ravikumar
continued from page 1
ubiquitous in the Hazleton area than it
should be, our team of researchers have put
together a collaborative myeloproliferative
disorders (MPDs) program to understand
the root cause of this epidemic using
Geisinger’s unique resources: our biobank
with annotated clinical data, the electronic
health record, and the investigators and
resources of the Weis Center for Research
and Henry Hood Center for Health
Research. These efforts are augmented by
the research that we are now undertaking
as the newest member of the MPD
Research Consortium, which is funded by
the National Institute of Health and brings
together investigators from the U.S. and
Europe to focus on this rare form of bone
marrow cancer.
RESEARCH CONNECTIONS
-3-
P. Vera Project
Receives Noteworthy
Support
Vincent Seamen, PhD. ASTDR/CDC
Toxicologist, Centers for Disease Control
and Prevention
The CDC’s Agency for Toxic
Substances and Disease Registry
(ATSDR) P. vera research program
consists of over 15 projects at
seven different institutions. In
addition to Geisinger Clinic,
these include the Pennsylvania
Department of Health, the
Pennsylvania Department of
Environmental Protection, Mt.
Sinai School of Medicine (NY),
Drexel University, the MPDResearch Consortium and the
National Program for Cancer
Registries at CDC. The projects
involve epidemiologic studies in
the Hazleton-Tamaqua area and
in other parts of Pennsylvania,
environmental testing, genetic
and biomarker studies, physician
awareness and education, and
improvements in cancer registry
reporting. In addition, funds were
provided to support a Community
Action Committee to give the
local communities an organized
voice in communicating with
state and federal agencies and the
various research groups. A total of
$8 million was made available for
P.vera research through the 2009
($5.5 million) and 2010 ($2.5
million) federal budget process,
largely through the efforts of local
elected representatives such as
Sen. Arlen Specter and Rep. Paul
Kanjorski. Although hundreds
of suspected cancer clusters are
reported each year in the U.S.,
this level of financial support is
extremely rare.
Staff Publications
These publications (from October 2009 – January 2010) feature Geisinger employees as authors. Publications jointly authored by a Geisinger employee and
employee(s) of other institutions feature an asterisk after the Geisinger employee’s name. When a Geisinger employee is the sole author, no marking exists.
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2. Berger JS, Roe MT, Gibson CMl, Kilaru
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P, Harrington RA, Armstrong PW. Safety
and feasibility of adjunctive antiplatelet
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a direct-acting and reversible P2Y12
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3. Blankenship JC. Quality metrics for
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4. Boscarino JA*, Adams RE. PTSD onset
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5. Cardella JF. The development process
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6. Cardella JF. Consensus document
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7. Choi H, Carlino R, Heiman G, Hauser
WA, Gilliam FG*. Evaluation of duration
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8. Coppola, C. Coppola: a pediatric
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12. Elston DM. Fungal foes:
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13. Elston D. Nontuberculous
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14. Elston DM. Update on cutaneous
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15. Elston DM. What is your diagnosis?
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16. Graham J., Estes B. What Standards
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17. Knapp CFI, Elston DM*. Botanical
briefs: Garden A. Cutis. 2009
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18. Langer RD. Efficacy, safety, and
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in managing menopausal symptoms.
J Am Board Fam Pract. 2009 SepOct;22(5):563-73.
19. Lauver LS, West MM, Campbell
TB, Herrold J, Wood GC. Toward
evidence-based teaching: Evaluating the
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in an associate degree nursing program.
Teaching and Learning in Nursing. 2009
Oct;4(4):133-8.
20. Ledwich LJ, Harrington TM,
Ayoub WT, Sartorius JA, Newman ED.
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15;61(11):1505-10.
21. Lin Q, Wang J, Childress C, Sudol
M, Carey DJ, Yang W. HECT E3
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ACK and regulates EFG-induced
degradation of EGFR and ACK.
Molecular and Cellular Biology Epub
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22. Moore M, Kirchner HL, Drotar
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23. Ndrepepa GN, Schulz S, Keta D,
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after percutaneous coronary intervention
with Bivalirudin or unfractionated Heparin
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24. Nischan J, Gatalica Z, Curtis M, Lenk
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Recent External Awards
This list includes new awards and competitive renewals from external agencies and Geisinger’s Clinical Research Fund from October 2009 through January
2010. To protect sponsors’ confidential information, dollar amounts for clinical trials and industry-sponsored agreements and some clinical listings are omitted.
If an award is inadvertently overlooked, please forward the information to Shawna Seger ([email protected]) for inclusion in the next issue.
Catherine Berlot, PhD
Molecular and Cellular Analysis of G Protein
Function in T Cells
Administrative Committee for Research
$100,000
David Carey, PhD
System-Wide Expansion of Bio-Banking
Activities at Geisinger Clinic
Administrative Committee for Research
$70,000
John Boker and Adele Spegman, PhD
Hands on Quality Improvement-The
Physician Nurses Relationship
Josiah Macy Foundation
$194,533
William Difilippo, MD
FSGS Associated with Chromosome 11:
Identification of a New Translocation
Administrative Committee for Research
$2,000
Cardiovascular Genetics. 2009
Dec;2(6):565-72.
nailing of femur fractures. Orthopedics
[Internet]. 2009 Aug;32(8):581. Available
from: http://dx.doi.org/10.3928/0147744720090624-17
25. Padigala KK, Hartle JE, Kirchner HL,
Schultz MF. Renal cortical thickness as
a predictor of renal function and blood
pressure status post renal artery stenting
Angiology 2009 Dec-2010 Jan;60(6):719-24
26. Park AM, Storm DW, Fulmer BR,
Still CD, Wood GC, Hartle JE, 2nd.
A prospective study of risk factors
for nephrolithiasis after roux-en-Y
gastric bypass surgery. J Urol. 2009
Nov;182(5):2334-9.
27. Pellitteri PK, Kennedy TL. Surgical
management of recurrent cancer in
the neck. In: Ferlito A, Robbins KT,
Silver CE, editors. Neck dissection:
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and neck cancer. San Diego: Plural
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28. Qian Z*, Lin HM, Chinchilli VM,
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29. Quinlan NP*, Kolotkin RL,
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30. Riehl JT, Widmaier JC. Techniques of
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32. Shah NR, Ogedegbe G. ACP Journal
Club. Review: first-line low-dose thiazides
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33. Sharma D, Bitterly TJ. Buffalo hump
in HIV patients: Surgical management
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34. Smith AL*, Pareja R, Ramirez
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Aug;61(4):339-46.
35. Smith JL, Lengerich EJ, Wood GC.
Injuries due to falls from hunters’ tree
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2009 Nov;37(5):433-6.
36. Stecker MM. The EEG as an
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2009 Oct;120(10):1777-81.
37. Stewart WF, Wood GC, Manack
A, Varon SF, Buse DC, Lipton RB
Employment and work impact of chronic
migraine and episode migraine. JOccup
RESEARCH CONNECTIONS
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Edward Gorak, DO
An Open-Label, Randomized, Parallel-Group
Study of Bendamustine Hydrochloride
and Rituximab (BR) Compared With
Rituximab, Cyclophosphamide, Vincristine,
and Prednisone (R-CVP) or Rituximab,
Cyclophosphamide, Doxorubicin,
Vincristine, and Prednisone (R-CHOP)
in the First-Line Treatment of Patients
continued on page 6
Environ Med. 2010 Jan;52(1):8-14.
38. Stone GW, Martin JL, de Boer M,
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BS, Weiner BH, Lansky AJ, Krucoff MW,
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Investigators. Effect of supersaturated
oxygen delivery on infarct size after
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39. Tromp G, Kuivaniemi H.
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40. Vijayaraman P*, Netrebko P*,
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K, Ellenbogen KA. Esophageal fistula
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41. Walgran, K. Don’t drunk-dial HR:
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42. Wood GC, Spahr R, Gerdes J, Daar
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Geisinger-New York University Collaborative Awards
Geisinger and the NYU Langone Medical Center are collaborating on joint research in personalized health care, including health services research, comparative effectiveness, genetic epidemiology and biomarkers, predictive modeling and behavior change. Each institution contributed $200,000 for a total of $400,000 to fund a group of
seed grants for the development of pilot data to support applications for extramural funding. The following projects were awarded funding under this program:
co-led by Geisinger investigator JB Jones, PhD, and New York
University investigators Gbenga Ogedegbe, MD, Antoinette
Shoenthaler
GHS $18,030; NYU $15,542
• Population-Based Evaluation of Primary Care Patients with MRSA in
Relation to Animal Feeding Operations in Pennsylvania, co-led by
Geisinger investigator Brian Schwartz, MD, PhD, and New York
University investigator Bo Shopsin, MD, PhD
GHS $33,284; NYU $ 2,500
• A Retrospective Study to Evaluate the Effect of Trends in Pain
Management Prescribing Behaviors on Falls and Hip Fractures in the
Elderly, co-led by Geisinger investigator Adele Spegman, PhD, and
New York University investigator Lydia Rolita-Metelsky, MD
GHS $25,689; NYU $522
• Predicting Congestive Heart Failure Using Casual Analysis of EHR
Data Geisinger Health System & New York University, co-led
by Geisinger investigator Walter Stewart, PhD, and New York
University investigator Bud Mishra, PhD
GHS $6,100; NYU $20,979
• Comparison of Obesity Alleles among Diverse Demographic Patient
Populations Geisinger Health System & New York University, coled by Geisinger investigator Christopher Still, DO, and New York
University investigator Manish Parikh, MD
GHS $10,000; NYU $0
• A Pilot Study of Predictors of Prescription Opiod Dependence
among NYU-Bellevue Hospital Outpatients: A Geisinger-NYU
Collaborative Study, co-led by Geisinger investigator Joseph
Boscarino, PhD, and New York University investigator Stephen
Ross, MD.
GHS $29,895; NYU $29,983
• Proactive Health Management and Prostate Cancer: Is Managed Care
Helpful and are Genomic Biomarkers Useful in Reducing the Burden
of Prostate Cancer, co-led by Geisinger investigator Porat Erlich,
PhD, and New York University investigator Richard B.Hayes, DDS,
PhD.
GHS $29,047; NYU $2,500
• Genetic Control of Weight Gain Following Gastric Bypass
Surgery Geisinger Health System & New York University, co-led
by Geisinger investigator Glenn Gerhard, MD, and New York
University investigator Harry Oster, MD
GHS $0; NYU $ 60,000
• Expanding Comparative Effectiveness Research in Orthopedics
by Capturing Uniform Measures of Patient-Reported Functional
Outcomes at Two Institutions, co-led by Geisinger investigator Jove
Graham, PhD, and New York University investigator James Slover,
MD.
GHS $28,654; NYU $15,542
• Developing the Paradigm for the Science of Healthcare Delivery,
Recent External Awards
continued from page 5
with Advanced Indolent Non-Hodgkin’s
Lymphoma (NHL) and Mantle Cell
Lymphoma (MCL)
Cephalon, Inc.
John Nash, MD
W2009-0137 Evaluation of CA125 and
HE4 Assays to Estimate the Risk of Ovarian
Cancer in Patietns Presenting to a General
Surgeon of Obstetrician/Gynecologist with
an Adnexal Mass (ROMA)
Fujirebio Diagnostics, Inc.
Jess Oren, MD
St. Jude Medical SJ4 Post Approval Study
St. Jude Medical Company
Jodi Schucker, MD
Preclampsia as a Disease of Genetic
Intereation between Mother and Fetus
Administrative Committee for Research
$99,902
Thomas Scott, DO
A 2x2 Factorial, Randomized, Multicenter,
Single-Blind Evaluation of Intracoronary
Abciximab Infusion and Aspiration
Thrombectomy in Patients Undergoing
Percutaneous Coronary Intervention for
Anterior ST-Segment Elevation Myocardial
Infarction (INFUSE AMI)
Atrium Medical Corporation
Nirav Shah, MD
Development of a Cardiovascular
Surveillance System in the CVRN
Kaiser Permanente
$204,762
Evaluating Impact of Chantix Adherence
on Quit Rates in the Geisinger Clinics;
Leveraging Links between the Electronic
Health Records and Claims Data
Phizer
Paul Simonelli, MD
Long Term Oxygen Treatment Trial
Temple University
$36,445
Kim Skelding, MD
A Prospective , Multicenter, Randomized,
Double-Blind Trial to Assess the Effectiveness
and Safety of 12 Versus 30 Months of Dual
Antiplatlet Therapy (DAPT) in Subjects
Undergoing Percutaneous Coronary
Intervention (PCI) with either Drug-Eluting
Stent (DES) or Bare Metal Stent (BMS)
Placement for the Treatment of Coronary
RESEARCH CONNECTIONS
-6-
Artery Lesions.
Harvard Clinical Research Institute
Azadeh Stark, PhD
Cancer Screening Effectiveness and Research
in Community-Based Healthcare
Group Health Center for Health Studies
$78,274
Walter Stewart, PhD
A Prospective Study of NT-proBNP, SelfReported Symptoms and HER Data as
Predictors of Heart Failure (HF) Diagnosis
Roche
Manuscript: Economics of Progression
Publication Agreement
Vedenta
$15,000
Tamara Vrabec, MD
Effect of Bariatric Surgery on Obesity-Related
Retinopathy
Administrative Committee for Research
$78,192
Shiming Zhang, PhD
Heme as a Target in Prostate Cancer Therapy
Administrative Committee for Research
$90,477