• ASH Leadership Election Results
• ASH's Alternative to NIH Policy on Public Access Removes Burden on Blood Authors
• ASH™ Updates COI Requirements for AM Speakers
• Bleeding Disorders in Women: A Damsel in Distress
• New Orleans: One Year Later
• ASH Honors Hematology Leaders
• CMS, P4P, PIMs, ABIM, ASH, and You
• Discover New Possibilities at the ASH Booth
• Annual Meeting Advance Registration Available Online

ASH Leadership Election Results

Vice-President Nancy Berliner, MD		Treasurer Linda J. Burns, MD
Councillor Brian J. Druker, MD		Councillor D. Gary Gilliland, MD, PhD

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ASH's Alternative to NIH Policy on Public Access Removes Burden on Blood Authors

Kanti Rai, MD

Dr. Rai is the President of ASH.

ASH™ has developed an agreement with the National Institutes of Health (NIH) that creates a new option for authors to comply with the NIH policy on enhanced access. All Blood authors that publish NIH-funded articles from May 2005 forward have no obligation to submit manuscripts to the NIH archive. Blood will do this on their behalf. ASH estimates that approximately 800 articles (from May 2005 to September 2006) will be deposited into the archive in this manner.

The new option, the PMC (NIH Portfolio) Archive Program, is the result of efforts by ASH and a group of nonprofit publishers to help authors improve compliance with the current NIH public access policy while maintaining the publisher-mandated access embargoes. The pilot project will provide NIH with final articles representing NIH-funded research for an internal-use archive at NIH.

The new program will achieve NIH’s goals of managing its research portfolio and developing a digital research archive, as well as increasing compliance with its submission policy, which was previously less than 4 percent. The program will also protect the integrity of the journal article of record, maintain business models that enable the Society to fund numerous educational and research programs, and, significantly, relieve Blood authors from the burden of submitting manuscripts to NIH.

ASH believes the PMC Archive program provides a better alternative for authors and journals than a mandated policy with a shorter embargo period. For more details, visit the Blood Web site.

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ASH™ Updates COI Requirements for AM Speakers

Armand Keating, MD

Dr. Keating is the Secretary of ASH.

This year, ASH has updated its conflict-of-interest requirements for annual meeting speakers and poster session presenters to remain in compliance with guidelines set forth by the Accreditation Council for Continuing Medical Education (ACCME), the accrediting body that allows ASH to provide continuing medical education (CME) credits to its attendees. The ASH leadership feels that it is imperative to continue to offer CME opportunities to physicians, and therefore finds it necessary to strengthen the Society’s policy on conflict of interest.

The Society now requires that all annual meeting speakers, session chairs, and moderators (including both invited speakers and abstract presenters) provide an oral disclosure and display a disclosure slide at the start of their presentations. If the speaker has no conflicts to report, a statement to that effect will be included on the conflict-of-interest disclosure slide. To make sure that the audience has time to absorb this information, disclosure slides must be shown for a minimum of five seconds. To ensure compliance, an audio-visual technician will advance both the title slide and disclosure slide for each presentation; after this, the technician will return control of the slides to the speaker for the rest of the presentation.

Beginning this year, all poster presenters must list conflict-of-interest information for themselves and all co-authors at the bottom of their poster. Again, if there are no conflicts to report, that will be indicated on the poster. In order to offer CME credits for the ASH Poster Sessions, all posters must include this conflict-of-interest disclosure.

The Society would like to thank all those presenting at the annual meeting for their understanding of the need for these updated conflict-of-interest requirements.

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Bleeding Disorders in Women: A Damsel in Distress

Margaret Ragni, MD, MPH

Dr. Ragni receives research support from Wyeth Pharmaceuticals.

Dr. Ragni is Professor of Medicine in the Division of Hematology/Oncology at the University of Pittsburgh.

Von Willebrand disease (VWD) is the single most common congenital bleeding disorder — it is also probably the single most difficult to diagnose. The problem is that the variability of symptoms and the lack of a single diagnostic test lead to underdiagnosis, significant morbidity, and poor quality of life, thereby constituting a major public health problem.

Type 1 VWD, which constitutes over three-fourths of all cases, occurs in up to 1 percent of the population and in up to 20 percent of women with menorrhagia. It is caused by a partial quantitative deficiency of von Willebrand factor (VWF), a multimeric protein that plays a key role in hemostasis — specifically platelet adhesion in platelet plug formation and factor VIII binding to prevent its degradation in the circulation. An autosomal disorder with variable penetrance, type 1 VWD is characterized by mucosal bleeding of variable severity and frequency, including menorrhagia, epistaxis, postpartum, and postoperative bleeding. Although genetic defects have been identified in some severe forms of type 1 VWD (usually these are primarily single-amino-acid substitutions leading to defective VWF secretion or clearance), the genetic defects underlying most forms of type 1 disease are less well defined than in more severe type 2 and 3 disease.

According to the VWD Subcommittee of the International Society of Thrombosis and Hemostasis, diagnosis is based on the presence of bleeding symptoms and low VWF activity (based on ristocetin platelet aggregation, VWF:RCoF, or collagen binding, VWF:CBA), low VWF antigen (VWF:Ag), low F.VIII activity (FVIII:C), and normal VWF multimers. These laboratory assays, however, may be variable and may also be affected by extragenic factors (hormones, exercise, ABO blood group). Further, they are difficult to perform and affected by sampling and storage conditions. Although in general the lower the VWF activity the greater the bleeding tendency, the diagnosis is difficult in those (the majority) with mildly decreased or borderline VWF levels that overlap with those in the normal control group. Further, the natural history of the disease is not well known and treatment remains suboptimal. Current therapies are invasive, of short-duration, and, if plasma-based, costly and subject to potential infectious agent risk. Among VWD women with menorrhagia, hormonal therapy is the treatment of choice, but it is nonspecific and ineffective in the majority.

Because of the clinical and laboratory variability, it has been argued that VWD is not truly a disease but rather a marker of bleeding tendency. Although the specificity of symptoms and laboratory assays for type 1 VWD are low, the lack of a test of sufficiently high specificity is not sufficient to deny the existence of type 1 VWD. According to Webster’s unabridged dictionary, type 1 VWD fulfills the definition of a disease, as “an impairment …that interrupts or modifies the performance of the vital function…being a response to…genetic anomalies…” Denying the existence of a disease on that basis is potentially dangerous for the female patient and the health care system caring for her. Without a diagnosis, which constitutes the focal point of prescribing medical therapy and communicating with physicians and affected patients, management would be difficult at best. Shepherding a patient through the current health care system without a diagnosis could severely jeopardize her health care, leading to delays in treatment, difficulty in obtaining insurance, refusal of medical reimbursement, and potentially alternative incorrect diagnoses — in a word, chaos in her health care.

Yet there is room for hope. First, a new quantitative bleeding scoring system has been recently developed with high sensitivity and specificity for VWD. The application of such a scoring system in, for example, the preoperative clinic could identify individuals who require VWD testing and hematology consultation, potentially averting bleeding complications. Secondly, several large multi-center phenotype-genotype studies of VWD kindreds in Europe and the U.S. are seeking to determine the relationship of clinical and genetic markers of VWD. This will hopefully improve our understanding of the pathophysiology and diagnosis of VWD. Finally, clinical trials of new hemostatic agents are underway, including a phase II study of interleukin-11, which has shown promise in the VWD dog model.

Future research studies to determine the optimal diagnostic and management algorithms for VWD are essential. Better approaches to the diagnosis of VWD in children, who have not yet developed bleeding symptoms, are greatly needed. Recombinant VWF should be a treatment option for individuals unresponsive to standard therapy and should not be dictated by the size of the affected population requiring it. Finally, optimization of patient-physician communication and empowerment of those with bleeding disorders is essential to assure their success in navigating a health-care system that doubts not only their symptoms, but also their diagnosis.

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New Orleans: One Year Later

Marc Kahn, MD

Dr. Kahn is Associate Dean of Admissions and Student Affairs at Tulane University Health Sciences Center.

August 29, 2005, the day that Hurricane Katrina made landfall, is a day that no New Orleans resident will ever forget. It was the day that changed lives forever. Within three-and-a-half weeks following the storm, the Tulane School of Medicine administration, with the help of Baylor College of Medicine and an alliance of Texas medical schools including Texas A&M, UTMB Galveston, and UT Houston, re-established the school 350 miles from home. Unfortunately, this was just in time for Hurricane Rita, which delayed the school’s opening by an additional week.

ASH has been terrific in the face of these disasters. Though the hurricane forced ASH to relocate its 2005 annual meeting from New Orleans to Atlanta, the Society remained committed to New Orleans. Through the ASH Katrina Relief Fund, the Society supported the city's convention bureau, restaurant, and tourism workers, and supported our fellowship program financially. They also provided funding to Louisiana State University Health Sciences Center. Importantly, they replaced books lost in the flood waters, waived dues for folks in affected areas, and provided financial assistance to attend the annual meeting.

It has now been more than a year since Hurricanes Katrina and Rita. New Orleans remains a “tale of two cities.” Parts of the city, including the French Quarter, remain unscathed and look like they did before the storms. Other parts have not changed since the storms and look as desolate and damaged as postwar cities. Many patients are finding doctors, but health care for the poor remains fragmented. We are seeing patients with more advanced malignancies as they have not been able to find health care providers. There is also a severe shortage of mental health providers in town. The number of available hospital beds is increasing each day, but Charity Hospital remains closed (although it is due to reopen this fall) and there are no mental health beds in the city.

We now see patients at several different hospitals that have not been used by Tulane before. There has also been a much smaller clinic volume than before the storms as a result of displaced folks. We did manage to keep all of our fellows in the program, but it is more difficult to recruit new fellows and residents.

At this point, New Orleans is not “better.” It will take years for health care to get back to where it was pre-Katrina. However, each day new businesses open, debris is removed, and storm damage is repaired. Importantly, people are returning home. To quote Dickens, “remember to the last, that while there is life, there is hope.” New Orleans is still alive; it is just a little under the weather.

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ASH Honors Hematology Leaders

Edward Benz, MD, and Ari Melnick, MD

Dr. Benz is President of the Dana-Farber Cancer Institute and Richard and Susan Smith Professor of Medicine, Professor of Pediatrics, Professor of Pathology, at Harvard Medical School.

Dr. Melnick is Assistant Professor, Department of Medicine (Oncology), and The Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Albert Einstein College of Medicine.

For over 30 years the American Society of Hematology (ASH) has recognized individuals in the field of hematology for their outstanding contributions. As two of the nominators of this year’s impressive awardees, we are pleased to highlight the winners of the Society’s Honorific Awards — the E. Donnall Thomas Lecture & Prize, the William Dameshek Prize, and the Henry M. Stratton Medal. These awards give the ASH membership a unique opportunity to step back and applaud great achievements that have lasting impacts on our field and the work we do.

In recognition of his fundamental contributions to science and his impact on the hematology field, Dr. Richard Stanley is the 2006 recipient of the E. Donnall Thomas Lecture & Prize. Dr. Stanley, the Renee and Robert A. Belfer Professor of Developmental Biology and Chairman of the Department of Developmental and Molecular Biology at the Albert Einstein College of Medicine, has made seminal discoveries in hematology research regarding the development and biology of macrophages, as well as regarding the nature of signal transduction through tyrosine kinase receptors. Specifically, Dr. Stanley isolated and identified colony-stimulating factor-1 (CSF-1) as the primary regulator of tissue macrophage and osteoclast production. He defined its receptor, physiology, and roles in development and neoplasia. He also identified and elucidated the function of several signaling molecules that act downstream of the CSF-1 receptor. Dr. Stanley has established several widely used mouse models to investigate the role of CSF-1 and the CSF-1 receptor in development and disease. These discoveries have taught us how monocytes and macrophages develop and grow, how they interact with their stroma, and how growth factors can direct the functions of hematopoietic cells. Dr. Stanley has also been an outstanding mentor to several generations of scientists. Dr. Stanley’s lecture, “Colony Stimulating Factor-1 in Development and Disease” will take place on Saturday, December 9, at 12:30 p.m. during the ASH annual meeting.

This year’s William Dameshek Prize will be awarded to Dr. Riccardo Dalla-Favera. Dr. Dalla-Favera, Director of the Herbert Irving Comprehensive Cancer Center of Columbia University and Jeremy and Percy Uris Professor and Director of the Institute for Cancer Genetics, has made seminal discoveries in the area of lymphoma biology. His discoveries in this area started with his central role in the identification of c-myc as the oncogene involved in the t(8;14) translocation characteristic of Burkitt’s and other lymphomas. More recently, Dr. Dalla-Favera discovered and cloned BCL6, a gene located on chromosome 3q27, which is the most frequently involved locus in diffuse large B-cell lymphomas (DLBCL). His subsequent work showing that BCL6 is a master regulator of B cell differentiation revealed a critical link between the normal functioning of the immune system and the development of DLBCL. Along these lines, Dr. Dalla-Favera found that the enzymatic machinery that generates high affinity antibodies by mutating the immunoglobulin loci in B cells often makes “mistakes.” These errors often result in the introduction of point mutations into other genes that can alter their function. Remarkably, the gene most commonly targeted in this way is BCL6, which as a consequence may become constitutively expressed. Dr. Dalla-Favera has gone on to show that this constitutive expression of BCL6 directly causes DLBCL. Taken together, much of what is known about the pathophysiology of aggressive lymphomas is due to Dr. Dalla-Favera’s seminal discoveries in this field. His impact on the field is even greater since, as a role model, he has inspired and encouraged many others. The William Dameshek Prize will be presented to Dr. Dalla-Favera on Tuesday, December 12, at 10:30 a.m. during the Presidential Symposium at the annual meeting.

The Henry M. Stratton Medal is being awarded to Dr. Jack Hirsh. A former Chairman of the Department of Medicine and the Founding Director of the Henderson Research Center, Dr. Hirsh (currently Professor Emeritus in the Department of Medicine at McMaster University in Hamilton, Ontario) established a thrombosis program at McMaster University that has been pre-eminent in thrombosis research for over three decades. He has trained scores of scientists who now head up thrombosis units throughout the world. Dr. Hirsh’s investigation of heparin and warfarin set the standards for their dosing and clinical use internationally. He also pioneered the standardization of laboratory monitoring and dosing of warfarin, thereby increasing its safety and expanding its use to patients that had been denied the benefit of this oral anticoagulant. His work elucidated the unique characteristics of low-molecular-weight heparin and uncovered its clinical advantages. Dr. Hirsh will be presented with the Henry M. Stratton Medal on Tuesday, December 12, at 10:30 a.m. during the Presidential Symposium.

Visit the ASH Web site if you would like to nominate an ASH member for one these prestigious awards in 2007.

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CMS, P4P, PIMs, ABIM, ASH, and You

Steven L. Allen, MD

Dr. Allen practices at North Shore University Hospital, Manhasset, NY.

The writing was on the wall when the King of Babylon received an unusual e-mail informing him that he had been counted, weighed, found wanting, and would not be recertified (Daniel 5:1-30). Hematologists can sympathize. We are proud of our reputation for providing high-quality consultative and patient-care services, but there is growing pressure to provide quantifiable evidence of quality which demonstrates performance and stimulates improvement.

Last year, the Executive Committee of ASH recognized this trend and requested that the Society’s Committee on Practice, chaired by Dr. Robert Weinstein, develop hematology-specific metrics that would provide relevant and fair criteria to measure performance. These quality-driven metrics will impact hematologists both financially and professionally. “Metrics” are a system of parameters that can be periodically measured in order to monitor the subject of interest. Metrics must be specialized by subject area to be valid and therefore require appropriate expertise in that subject area to be properly designed.

ASH’s initial effort in this field was in response to a request from the Centers for Medicare and Medicaid Services (CMS) to develop hematology-specific Pay-for-Performance (P4P) metrics. A task force, chaired by Dr. Kenneth Adler and including Drs. Lawrence Solberg, Jr., Vincent Picozzi, Samuel Silver, Timothy Miley, and myself, was created. Metrics for several malignant and benign hematologic disorders were developed by the task force, and its proposal was well-received by CMS.

In the midst of the task force’s effort and highlighting the quantifiable evidence trend, the American Board of Internal Medicine (ABIM) announced new recertification requirements for physicians, including the need to secure 100 points (20 knowledge, 20 practice improvement, 60 elective) by completing self-evaluation modules. These modules must be a mix of medical knowledge and Practice Improvement Modules (PIMs). Capitalizing on the experience already gained in the P4P effort, the task force was designated to develop hematology PIMs. ABIM requires that the PIMs have the physician collect actual patient data measuring performance on at least five metrics for a minimum of 10 patients with the selected condition. The physician must then choose one metric, design a plan to improve in that area, and, at a designated future date, re-measure performance in that metric. Points are then awarded by the ABIM. While several PIMs are being finalized, a PIM for myelodysplasia has been approved and can be reviewed on the ASH Web site.

These metrics will now undergo further refinement through a collaborative arrangement with the American Medical Association (AMA). Congress has designated the AMA’s Physician Consortium for Performance Improvement, along with the National Quality Forum, to develop and approve performance measures which will have a major role in future Medicare programs. ASH is the lead organization in this process for hematologists, and members of the task force will be working with the Consortium.

Much has been accomplished in only one year, and the task force is now developing additional measures for multiple myeloma to be released within the next several months. In addition to the evaluation component, each set of measures will be accompanied by physician resources and educational materials. With these initiatives, the Society is doing its best to ensure that hematologists will not succumb to the fate of the King of Babylon.

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Discover New Possibilities at the ASH Booth

You know about the groundbreaking science at ASH’s annual meeting and you’ve read the world’s leading hematology journal, Blood, but have you explored all the opportunities that the Society has to offer? At the ASH booth, you can learn how to honor a mentor, nominate an institution for participation in the International Outreach Initiative, purchase a copy of the ASH-SAP, or apply for funding for a cross-cultural experience conducting research abroad. For more information on the ASH annual meeting, visit the ASH Web site.

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Annual Meeting Advance Registration Available Online

Avoid lines at on-site registration counters and benefit from a discount by registering for the meeting prior to November 6, 2006. ASH encourages meeting attendees to register online, but registration can also be made by faxing the ASH registration form with credit card payment to 888-273-5706 (U.S. and Canada toll-free number) or 703-631-6288. The registration form may also be mailed along with the appropriate fees to the ASH Registration Center. For more information, visit the ASH Web site.

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