PROCEEDINGS FROM
ASBMT CORPORATE COUNCIL MEETING
September 23-24, 2012
Hyatt Carmel Highlands
Carmel, CA
Corporate
Participants:
Tara Clark (Miltenyi Biotec), J. Frank Glavin (Fresenius Biotech), Jim Holmes (Millennium),
John Jarrett (Amgen), Dr. Richard Kadota (Sanofi), Dr. Kai Pinkernell (Miltenyi Biotec),
Marina Rajenova (Celgene), Sharon Roell (Otsuka) and Stephen Van Komen (Bristol-Myers
Squibb)
ASBMT
Participants:
Drs. Armand Keating (Chair), Linda Burns, Corey Cutler, Marcos de Lima, Robert Korngold,
Keith Sullivan and Daniel Weisdorf
Guests:
Drs. Dennis Confer (NMDP), David Hoganson (Washington University, St. Louis), Jennifer Malin
(WellPoint), Mohamed Sorror (Fred Hutchinson Cancer Research Center)
Staff:
Thomas Joseph and Bob Krawisz
This report summarizes the information that was gathered at the ASBMT Corporate Council Meeting. Speaker
presentations are available on the ASBMT Website: www.asbmt.org.
I.
Bone Marrow or Peripheral Blood: When is the Evidence Enough?
Dr. Dennis Confer, NMDP (BM) and Dr. Corey Cutler, Harvard Medical School (PBSC)
Drs. Confer and Cutler presented data on usage trends and evidence to support the advantages and
disadvantages of each stem cell source.
Learning Objectives – Participants were able to understand:
1) Stem cell source usage trends.
2) Patient and donor preferences.
3) Issues pertaining to GVHD and relapse.
4) If GVHD is as bad as it seems.
5) The results of Marrow vs. PBSC in matched sibling transplants (9 randomized trials).
6) Considerations for determining the optimal stem cell source.
Considerable discussion ensued and in response to a question from the moderator, Dr Keating,
leaders/representatives of several transplant programs indicated that they would change practice by using
bone marrow instead of mobilized peripheral blood grafts. Interest was expressed in a questionnaire to
be sent to the ASBMT membership (possibly via eNews) after the publication of the manuscript by
Dr. Claudio Anasetti regarding a change in practice at his center.
Dr. Dennis Confer is Chief Medical Officer of the National Marrow Donor Program
Dr. Corey Cutler is Assistant Professor of Medicine at the Harvard Medical School and a member of the
ASBMT Board of Directors.
II.
Tissue Engineered Lung Technology
Dr. David Hoganson, Washington University, St. Louis
The clinical need for tissue-engineered organs is based on the dramatic shortage of organs for
transplantation. For all organs, this shortage continues to grow. The waiting list for organs in the United
States in 1989 was 19,095 patients; 20 years later the list has grown to over 100,000 patients.
Chronic lung disease affects nearly 750,000 Americans. The only treatment option for end stage lung
disease is lung transplantation, which is performed only 1,400 times a year due to organ shortage and
patient ineligibility due to medical comorbidities. For patients awaiting lung transplantation, the average
waiting time is over 14 months, with 11.3% of these patients dying before they receive an organ. The
quality of life for patients with end stage lung disease is often severely limited by their disease as the daily
activities of living constitute tremendous time and effort. There is a clear clinical need for a lung assist
technology that can serve as a bridge to transplantation or destination therapy and allow ambulation and
hospital discharge. Dr. Hoganson covered breakthroughs in development of lung assist device technology
with physiologic blood flow developed on a tissue engineered scaffold platform.
Learning Objectives – Participants were able to understand:
1) Introductory biomimetic design principles.
2) Developments of a tissue engineered lung with a vascularized scaffold approach (all approaches to
tissue engineering before 1998 were angiogenesis dependent).
3) The challenge of vascularization. How the architectural of the engineered lung approach mimics that
of the native alveolus where there are capillaries immediately adjacent to the alveolus and gas
exchange occurs across the respiratory membrane consisting of the lung epithelial cells, basement
membrane and endothelial cells of the capillaries.
4) Use of pediatric lung assist devices: how developments of neonatal total lung support devices are used
to treat Bronchopulmonary Dysplasia.
Issues Requiring Follow-up:
1) Evaluate lessons learned in biomimetic design principles that can be applied to blood and marrow
transplantation and cellular therapy.
2) Explore transplantation of groups of cells to treat diseases or complications.
Dr. David Hoganson is a Cardiothoracic Surgery Fellow, Washington University, St. Louis and was
previously a biomedical engineering researcher. He is renowned for his research on tissue engineered lung
technology.
III.
Comorbidities and Quality of Life
Dr. Mohamad Sorror, Fred Hutchinson Cancer Center
Dr. Sorror’s research is focused on studying the impacts of medical comorbidities on outcomes of
hematopoietic cell transplantation (HCT) for hematologic malignancies in order to improve decisionmaking and lessen the HCT morbidity and mortality. A new HCT-specific comorbidity index (HCT-CI)
was developed to capture comorbidities at time of HCT and to predict outcomes. Current research is
focused on validating the discriminative capacity of this index among patients transplanted at different
institutions. The index is being modified by adding biomarkers and objective laboratory data to further
improve its prognostic value. The index is also used to investigate the biologic link between pre-transplant
comorbidities and post-transplant toxicities, graft-versus-host disease, causes of death and quality of life.
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Dr. Sorror’s research also involves new methods to maximize the benefits of nonmyeloablative
conditioning and allogeneic HCT for older and medically infirm patients diagnosed with chronic
lymphocytic leukemia or lymphoma. One approach is investigating whether the addition of anti-CD20
monoclonal antibody (rituximab) to the nonmyeloablative conditioning could improve survival. Another
approach is combining high-dose myeloablative autologous HCT, for disease debulking, with allogeneic
HCT from HLA-haploidentical donor using nonmyeloablative regimen, for continued graft-versus disease
consolidation.
Learning Objectives – Participants were able to understand:
1) A new method of classifying prognostic comorbidity and longitudinal studies.
2) If age matters anymore for HCT eligibility with comorbidity information available.
3) The outcomes of two multi-institutional validation studies (Seattle Consortium and CIBMTR).
4) Issues pertaining to the quality of life (QOL) after allogeneic HCT.
5) The impact of comorbidities on QOL among long-term survivors after allogeneic HCT
Issues Requiring Follow-up:
1) Impacts of specific organ comorbidities on QOL.
2) Impact of HCT-CI/comorbidities on early QOL after HCT.
3) Different approaches to comorbid survivors?
4) Prospective studies are warranted:
o
Trajectories of QOL.
o
Pre-transplant assessment of comorbidities + QOL.
o
Post-HCT assessment of QOL: 6, 12, and 24 months.
5) Payers are not asking about the comorbidity index. Additional communication may be required.
6) Determining the impact of comorbidities on institutional acceptance of patients.
Dr. Mohamed Sorror is a member of the Fred Hutchinson Cancer Research Center and an expert on
comorbidities and quality of life.
IV.
Transplants in Older Patients
Dr. Keith Sullivan, Duke University Medical Center
Hematopoietic stem cell transplantation (HCT) for treatment of hematologic malignancies has traditionally
been offered as curative therapy to children and young adults while, ironically, these diseases are more
prevalent in older patients. Decisions to place age limits on HCT have been driven by evidence of higher
morbidity and mortality in older age groups based on regimen-related toxicity, higher risk of short-and
long-term complications of therapy and higher incidence of comorbidities which may increase transplant
risk.
Advances in hematopoietic cell transplantation have reduced mortality by reducing the period of
neutropenia following transplantation, and by reducing the toxicity of conditioning regimens. In light of
these advances, physicians are now more likely to consider 'older' patients on an individual basis, and to
consider physiological age, rather than chronological age in making decisions about suitability of
individual patients as transplant candidates.
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Learning Objectives – Participants were able to gain insights on:
1) Trends in life expectancy and cancer cases.
2) Progress in reducing cancer deaths.
3) Trends in transplantation by age.
4) Allogeneic transplantations by conditioning regimen intensity and patient age.
5) Older age (60-75 years) risk factors for adverse outcomes following NMA allogeneic HCT.
6) Cost of BMT.
7) Life, but at what cost?
8) Medical services that are not worthwhile.
Issues Requiring Follow-up:
1) Determine if age has a negative impact on prognosis because of:
a.
Referral bias
b. Under-treatment
2) Explore if age should impact treatment decision?
3) Explore developing a better risk stratification for older patients based on:
a.
Comorbidity
b. Performance status
c.
Social support
d. Not on age alone
4) Explore development of a National Policy to eliminate procedures without evidence of benefit.
5) Explore local innovations to discover care that is faster, cheaper and better.
6) Considerable discussion ensued and interest was expressed in having ASBMT and the BMT
community consider establishing a list of 3 to 5 things/procedures that BMT clinicians should NOT do
based on the patient, situation and/or evidence of benefit
Dr. Keith Sullivan is a Past-President of ASBMT and serves as the James B. Wyngaarden Professor of
Medicine at Duke University Medical Center where he served as Chief, Division of Medical Oncology and
Transplantation. Dr. Sullivan also serves as the Director of Long-term Follow-up and Information Research
Program, in the Division of Cellular Therapy. He has extensively published in the area of bone marrow
transplantation with over 400 peer-reviewed publications and book chapters.
V.
Hematopoietic Cell Transplantation in 2020: A System Capacity Initiative
Dr. Dennis Confer, NMDP
Hematopoietic cell transplantation (HCT) is the only known curative therapy for many patients with lifethreatening malignant and non-malignant hematologic diseases. More than 20,000 transplants are
performed in the United States yearly and the NMDP estimates that the demand for unrelated donor
transplantation will double over the next decade.
In September 2009, the NMDP organized a three-year program called the System Capacity Initiative (SCI)
to figure out how our healthcare system could accommodate the growing number of patients in need of
HCT. As survival for transplant has improved, more patients are eligible than ever before. The NMDP is
leading the SCI, which involves representatives of many disciplines coming together to address issues such
as workforce shortages, space constraints, patient access barriers, and other pressing issues that prevent
appropriate access to transplantation now and in the future.
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Learning Objectives – Participants were able to understand:
1) The growth of BMT transplants in the United States.
2) The overall physician shortage – what are the root causes?
3) Factors driving physician demand.
4) BMT Physician supply and demand projections through 2020.
5) Factors attracting Fellows to the field.
6) Strategies to increase the supply of BMT physicians.
7) NMDP Working Group recommendations.
8) Potential replication of the study in other fields.
Issues Requiring Follow-up:
Implement the recommendations of the SCI working groups.
VI.
Should ASBMT Develop a BMT Board Certification?
Dr. Linda Burns, University of Minnesota
The ASBMT Task Force on Board Certification, chaired by Dr. Linda Burns, was charged with
evaluating and making a recommendation to the Executive Committee on whether to pursue certification
of BMT as a subspecialty. To accomplish this assignment, the Task Force took the following steps:

Conducted a survey of ASBMT members to gauge interest in and opinions about certification.

Reviewed factors that potentially favor certification – such as enhanced professional stature and
recognition by patients, other physicians and third-party payers of acquired skill sets.

Reviewed factors that potentially disfavor certification – such as costs, administrative burden and
impact on recruitment.

Explored with the American Board of Internal Medicine (ABIM) and the American Board of Pediatrics
(ABP) the steps that would have to be taken to seek certification.
A summary of the conclusions reached were the following:

There was no clear consensus.

There were strong sentiments for and against board certification.

The majority of members agreed with need for additional training (6-12 months) for a BMT career

Discussions with ABIM revealed the need for valid/reliable test questions and an adequate number of
test takers to justify the cost and maintenance of the exam.
Learning Objectives – Participants were able to gain an understanding of:
1) The potential benefits and barriers of BMT Board Certification.
2) Subspecialties with certifying Boards.
3) Results of the ASBMT membership survey (32% response rate).
4) The preliminary conclusions of the Task Force.
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Issues Requiring Follow-up:
1) Continue implementation of new guidelines for training (pediatrics and adult):
a.
Approved by ASBMT Board and published in BBMT.
b. Categorized within ACGME six core competencies.
c.
Will be presented at Tandem 2013.
d. Could be used as basis for establishing ACGME or ASBMT accredited programs.
2) Continue implementation of Practice Improvement Modules (PIMs)
a.
20 ABIM Maintenance of Certification (MOC) credits.
b. Chronic Graft Versus Host Disease.
c.
Infections.
d. Addresses need for Quality Improvement.
3) Secure a final decision on the question: Should Blood and Marrow Transplantation become a
recognized subspecialty of internal medicine and pediatrics with ACGME accredited training programs
and certifying board examinations.
Dr. Linda Burns is a Professor in the Department of Medicine, Division of Hematology, Oncology and
Transplantation at the University of Minnesota. She is also a member of the ASBMT Board of Directors.
VII.
Should ASBMT Develop a BMT Board Certification?
Dr. Jennifer Malin, WellPoint, Inc.
Dr. Malin provided an overview of the Blue Distinction Program to explain how physician board
certification is used as one of the selection factors for hospitals and medical facilities. Blue Distinction is a
national designation awarded by Blue Cross and Blue Shield companies to hospitals and medical facilities
that have demonstrated expertise in delivering quality healthcare in the areas of bariatric surgery, cardiac
care, complex and rare cancers, knee and hip replacement, spine surgery and transplants. The designation
is based on objective, evidence-based selection criteria established in collaboration with expert physicians
and medical organizations.
Learning Objectives – Participants were able to gain insights on:
1) The framework for measuring quality care.
2) The Blue Distinction selection criteria.
3) Market factors driving program change.
4) Importance of physician Board Certification from a payer perspective.
Issues Requiring Follow-up:
Additional payers should be contacted to obtain their views on BMT physician Board Certification.
Dr. Jennifer Malin is the Medical Director Oncology for WellPont, Inc.
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VIII.
Challenges of Outcomes Reporting and Analysis
Dr. Daniel Weisdorf, University of Minnesota
CIBMTR holds the contract for the Stem Cell Therapeutic Outcomes Database (SCTOD), awarded by the
Health Resources and Services Administration of the U.S. Department of Health and Human Services.
The SCTOD is part of the C.W. Bill Young Cell Transplantation Program (Program), authorized by the
Stem Cell Therapeutic and research Act of 2005 (Public Law 109-129).
As the contract holder, the CIBMTR is charged with collecting data on all allogeneic (related and
unrelated) hematopoietic cell transplantations (HCTs) performed in the United States, and on all HCTs
done with products procured through the Program but performed outside of the United States. The SCTOD
database allows analysis of Program use, center-specific outcomes, size of donor registry and cord blood
inventory, and patient access to HCT. Because of the collaboration and dedication of physicians and data
managers at transplant centers, the field of transplantation already had in place a tremendous voluntary data
submission mechanism. The SCTOD builds upon the existing CIBMTR infrastructure and expertise for
data collection, management and analysis.
In managing the SCTOD, the CIBMTR collaborates with transplant centers to:





Develop data reporting requirements for allogeneic transplants in the United States.
Manage a related donor-recipient research sample repository.
Design and maintain systems to collect data and make it publicly available.
Study center-specific outcomes.
Collect data on novel therapeutic uses of hematopoietic stem cells
Learning Objectives – Participants were able to gain insights on:
1) The challenges of outcomes reporting -- complex, imprecise and often misinterpreted.
2) Outcomes research.
3) Clinical versus outcomes research.
4) Methods for adjusting for survival risk factors.
5) Predictability of risks and survival.
6) The difficulties in reporting and interpreting outcomes: heterogeneity of patients, small sample sizes,
timeliness of the data and data collection.
7) Costs and cost-effectiveness in BMT – why is BMT so expensive?
8) Tips for outcomes research.
Issues Requiring Follow-up:
1) Improve data collection.
2) Improve data outcomes analysis.
3) Educate patients and payers on use of outcomes data.
Dr. Daniel Weisdorf is the Immediate Past-President of ASBMT and Director of the Adult Blood and
Marrow Transplant Program at the University of Minnesota. He serves as the Scientific Director of the
National Marrow Donor Program
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IX.
Getting Cellular Therapies into the Clinical Routine: Not Your Average FDA Approval
Dr. Kai Pinkernell, Miltenyi Biottec, Inc.
The FDA Cellular, Tissue and Gene Therapies Advisory Committee reviews and evaluates available data
relating to the safety, effectiveness, and appropriate use of human cells, human tissues, gene transfer
therapies and xenotransplantation products which are intended for transplantation, implantation, infusion
and transfer in the prevention and treatment of a broad spectrum of human diseases and in the
reconstruction, repair or replacement of tissues for various conditions.
The Committee consists of 13 voting members including the Chair. Members and the Chair are selected by
the Commissioner or designee from among authorities knowledgeable in the fields of cellular therapies,
tissue transplantation, gene transfer therapies and xenotransplantation including biostatistics, bioethics,
hematology/oncology, human tissues and transplantation, reproductive medicine, general medicine and
various medical specialties including surgery and oncology, immunology, virology, molecular biology, cell
biology, developmental biology, tumor biology, biochemistry, rDNA technology, nuclear medicine, gene
therapy, infectious diseases, and cellular kinetics.
U.S. Regulatory Framework is a 3-Tiered System
Statutes (Laws):
Passed by Congress and signed by the President
 Food, Drug & Cosmetic Act (FD&C Act)
 Public Health Service Act (PHS Act)
Regulations (details of the law):
Written by FDA and approved by the Executive Branch
 21 CFR (Code of Federal Regulations)
Guidance (FDA’s interpretation of the Regulations):
Written and approved within FDA
 Advice non-binding on FDA or sponsor
Approved Cellular Products in the U.S.
Cellular Therapy Product
Carticel®
Provenge® (Sipuleucel-T)
Laviv™ (Azficel-T)
Apligraf (Graftskin)
OrCel
Dermagraft
Dermagraft-TC
Epicel
Integra Artificial Skin
Manufacturing Company
Genzyme
Dendreon
Fibrocell Technologies
Organogenesis
Ortec
Advanced BioHealing
Advanced Tissue Science
Genzyme
Integra LifeSciences Corp.
Learning Objectives – Participants were able to gain insights on:
1) An overview of Miltenyi Biotec products and services.
2) The complexity of cellular therapeutics.
3) Differences in centralized (drug model) and campus manufacturing.
4) What is important to make cellular therapy successful?
5) Regulatory issues.
6) What the ASBMT should consider.
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Issues Requiring Follow-up:
1) Education of / interaction with the regulators about cell therapies.
2) Definition of standards.
3) Risk/benefit evaluation.
4) Simplification of treatment regulations that considers the “one patient one product” reality
(i.e. “manufacturing”.
5) Securing opinions from medical ethicists on having control groups for “last resort” therapies.
Dr. Kai Pinkernell is Global Head of Clinical Business for Miltenyi Biotec in Germany.
X.
Major Challenges Facing the Pharmaceutical Industry
Dr. Richard Kadota, Sanofi
Four major challenges facing the complex Pharma industry include the decline in the discovery, approval
and marketing of new chemical entities (NCE) with fewer and fewer blockbuster drugs making it to the
market, competition from generic drugs, regulatory pressures and the weak growth in the US market (the
largest market). In Addition, Dr. Kadota pointed to several challenges facing HCST:

Traditional drug development may require more than 10 years and up to a $1.8B investment.

Pharma does not have a sustainable business model: (especially challenging incentives for new
HSCT medications due to market size).

The factors to be considered one decade ahead: probability of technical success, regulatory
success, marketing approval and prescription by physicians.
Learning Objectives – Participants were able to gain insights on:
1) Life cycles of HSCT products.
2) Registration, trials and acquisition.
3) Regulatory approval and launches.
4) Challenging incentives to develop new HSCT medications
5) Regulatory issues.
Issues Requiring Follow-up:
1) Explore the feasibility of sponsoring a symposium/workshop on development of “end points.”
2) The new initiative funded by 10 large international pharmaceutical companies (Abbott, AstraZeneca,
Boehringer Ingelheim, BMS,GSK, J&J, Lilly, Pfizer, Roche/Genentech & Sanofi)
3) Five initial project goals of the Pharma initiative:
a. Shared user interface for easier access by investigators.
b. Mutually recognized trial site qualification and training.
c. Standardized site monitoring.
d. Uniform clinical data format.
e.
Model for supplying trials for comparator drugs.
4) Add academia, regulatory agencies, CROs and patient advocacy groups to the Pharma initiative.
Dr. Richard Kadota is Medical director of Oncology Transplant, global Medical affairs for Sanofi.
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XI.
Adjournment
It was agreed that a follow-up meeting should be scheduled during the 2013 BMT Tandem Meetings in
February in Salt Lake City. The meeting adjourned on Monday, September 24 at 4:00 p.m. (PDT).
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