Annual Meeting-American Society of Hematology

48th ASH™ Annual Meeting and Exposition
December 9-12, 2006

Orange County Convention Center
Orlando, Florida

Education Program

Education Program
Co-Chairs:

Charles Linker, MD, University of California, San Francisco, CA

Charles A. Schiffer, MD, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI

The 2006 Education Program will be held Saturday, December 9, and Sunday, December 10. Each session will be offered twice unless otherwise noted. Chapters based on these sessions will be published in the Education Program Book, Hematology 2006.

Iron in Hematology

Chair:

Mark Fleming, MD, DPhil, Children’s Hospital, Boston, MA

Speakers:

Tomas Ganz, MD, PhD, David Geffen School of Medicine at the University of California – Los Angeles, Los Angeles, CA
Hepcidin and Iron Metabolism

Pierre Brissot, MD, University Hospital Pontchaillou, Rennes, France
Current Approach to Hemochromatosis

Alan R. Cohen, MD, Children’s Hospital of Philadelphia, Philadelphia, PA
Iron Chelators: Recent Advances

Nearly two-thirds of the iron in the body is present in heme in hemoglobin, and while most hematologists confront iron deficiency anemia on a weekly, if not daily, basis, the pathogenesis and treatment of iron overload disorders, which largely affect the liver – the primary site of iron storage – are more obscure. This session will focus on recent advances in the basic science of iron metabolism, the genetics and treatment of genetic iron overload disorders, and the clinical pharmacology of iron chelation therapy for the treatment of iatrogenic iron overload, with a particular emphasis on the liver.

Dr. Tomas Ganz will review the molecular mechanisms of iron metabolism, concentrating on the central role of hepcidin, a peptide hormone produced by the liver that regulates cellular iron export. He will discuss physiologic factors, such as hypoxia, iron stores, and inflammation, which regulate hepcidin production and their downstream effect on systemic iron metabolism, as well as how dysregulated hepcidin gene expression contributes to the pathogenesis of hereditary iron overload and the anemia of inflammation.

Dr. Pierre Brissot will briefly review the diverse genetic causes of primary, genetic hemochromatosis syndromes, touching on clinically important distinctions between each of them. He will then discuss practical aspects of the laboratory diagnosis, treatment, and measurement of response to therapy of primary hemochromatosis and how the approach differs from that to secondary iron overload.

Dr. Alan Cohen will describe the indications for chelation therapy in patients with transfusional iron overload. He will briefly review the long-term benefits of deferoxamine and will describe the appropriate use of intravenous chelation therapy and the data supporting the use of oral iron chelators recently approved for clinical use.

Sickle Cell Anemia

Chair:

Marilyn J. Telen, MD, Duke University Medical Center, Durham, NC

Speakers:

Paul S. Swerdlow, MD, Wayne State University, Detroit, MI
The Role of Exchange Transfusion in Sickle Cell Anemia

Orah S. Platt, MD, Harvard Medical School, Boston, MA
Management of Cerebrovascular Disease

George F. Atweh, MD, Mount Sinai School of Medicine, New York, NY
Induction of Fetal Hemoglobin in the Treatment of Sickle Cell Disease

Hemoglobinopathies, and specifically sickling hemoglobinopathies, constitute a large percentage of inherited hemolytic anemias in the United States and worldwide. While patients with hemoglobin S syndromes are living longer, their increasing accumulation of end-organ complications requires ever more efficacious and finely tuned medical management. This session will address management strategies that are part of our present as well as perhaps future armamentarium for combating the sequelae of sickle cell disease.

Dr. Paul Swerdlow’s talk will contrast exchange transfusions with simple transfusions, exploring the physiology of red cell exchange and the reasons why exchange transfusions are required in certain circumstances. Practical methods of exchange, both manual and automated, will be reviewed, along with potential complications. Appropriate target values of hemoglobin level and percentage hemoglobin A and hemoglobin S will be discussed, as will issues related to iron overload. Current, controversial, and possible future indications for exchange transfusion will also be explored.

Dr. Orah Platt will discuss how, as the overall health of patients with sickle cell disease improves and diagnostic techniques become more sensitive, physicians are seeing patients with an increasingly wide range of subtle and not-so-subtle brain injury. While emphasizing strategies to prevent the most devastating brain injury, stroke, Dr. Platt will also draw on lessons from pathophysiology to discuss potential options for patients who don’t fit easily into the typical stroke paradigm designed for children.

Dr. George Atweh will discuss the pharmacological induction of fetal hemoglobin in the treatment of sickle cell disease. He will provide a brief background on the history of this field and the seminal studies that led to the approval of hydroxyurea in the treatment of patients with this disease. He will provide some insights into the mechanisms of induction of fetal hemoglobin that are being acquired through the study of the epigenetic effects of these agents on histone acetylation and DNA methylation in the globin gene clusters. He will also discuss the effects of the inducers of fetal hemoglobin on the hemoglobin composition of red blood cells and the effect of the changes in hemoglobin composition on the pathophysiology of sickling. He will conclude with a discussion of where this field is today and where it has to go in the future in order for these pharmacological therapies to make a larger impact on the natural history of sickle cell disease.

Acute Lymphoblastic Leukemia in Adults and Children

Chair:

Charles Linker, MD, University of California, San Francisco, CA

Speakers:

Stephen E. Sallan, MD, Dana-Farber Cancer Institute, Boston, MA
Lessons from Treatment of Acute Lymphoblastic Leukemia in Adolescents and Young Adults

Nicola Goekbuget, MD, J.W. Goethe University Hospital, University of Frankfurt, Frankfurt, Germany
Treatment of Adult Acute Lymphoblastic Leukemia

Ching-Hon Pui, MD, St. Jude’s Children’s Research Hospital, Memphis, TN
Prophylaxis and Treatment of Central Nervous System Disease in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most important malignancy in childhood, and most of the information regarding treatment has been learned from the pediatric experience. ALL is also an important disease in adults, and physicians treating adult patients have much to learn from their pediatric colleagues.

Dr. Stephen Sallen will discuss the current status of treatment of pediatric ALL from the perspective of the Dana-Farber Consortium, with particular emphasis on the treatment of adolescents and young adults. Recent retrospective analyses have demonstrated a superior outcome for adolescents treated with pediatric rather than adult protocols, and Dr. Sallen will discuss the lessons that can be applied from the pediatric experience. He will review the role of asparaginase, which is used more aggressively in pediatric programs than in adults.

Dr. Nicola Goekbuget will discuss the current status of treatment of adult ALL from the perspective of the German ALL Study Group. She will focus on treatment of the younger patient. Important biologic differences exist among the group of T-phenotype ALL, which comprise 20 percent of adult ALL, and these factors can be used to direct treatment choices. She will explore the extent to which modifications of current chemotherapy can improve outcomes.

Dr. Ching-Hon Pui will discuss the important area of Central Nervous System (CNS) disease in pediatric ALL, with conclusions that may be applied to adult disease as well. He will discuss the diagnosis of CNS disease and prognostic factors for the development of CNS relapse. He will discuss regimens for prophylaxis of CNS disease and give practical tips for patient management. Lastly, he will discuss treatment of overt CNS relapse.

Marrow Failure Syndromes

Chair:

Jeffrey M. Lipton, MD, PhD, Schneider Children’s Hospital, Albert Einstein College of Medicine, The Feinstein Institute for Medical Research, New Hyde Park, NY

Speakers:

Neal S. Young, MD, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
Biology of Aplastic Anemia

Akiko Shimamura, MD, PhD, Children’s Hospital Boston, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA
Inherited Bone Marrow Failure Syndromes

Judith Marsh, MD, St. George’s Hospital, St. George’s University of London, London, United Kingdom
Making Therapeutic Decisions in Adults with Aplastic Anemia

Acquired and inherited bone marrow failure is a heterogeneous group of diseases of differing pathophysiology. Recent advances in molecular and cellular biology have resulted in a more complete understanding of these disorders, leading to improved diagnosis and treatment.

Dr. Neal Young will review our understanding of the pathophysiology of acquired aplastic anemia, emphasizing three areas of current research. First, the immune basis of marrow destruction is now being analyzed at the molecular level. T-cell oligoclonality in most patients is strong evidence for an antigen-driven T-cell response and may be helpful in assessing the activity of immunosuppressive therapies. T-cell signal transduction pathways are abnormal in some patients with aplastic anemia. Second, genetic studies of the target hematopoietic compartment have implicated genes of the telomere repair complex as determinants of constitutional marrow failure syndromes and as risk factors for apparently acquired aplastic anemia. Third, in vitro studies have provided tentative pathophysiologic mechanisms for the evolution of cellular clones and the development of paroxysmal nocturnal hemoglobinuria and aneuploid myelodysplasia from marrow failure.

Dr. Akiko Shimamura will describe recent advances resulting from the identification of the genes responsible for the inherited marrow failure syndromes. The interpretation of genetic testing should be guided by an understanding of the limitations of such testing for each disorder. The possibility of an inherited basis for marrow failure must be considered for adults as well as children with aplastic anemia. Shared molecular themes are emerging from functional studies of the genes underlying the different inherited disorders. Genomic instability may result from impaired DNA repair in Fanconi anemia or telomere dysregulation in dyskeratosis congenita. Mutations affecting ribosome assembly or function are associated with Diamond-Blackfan anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome. These findings raise new questions about the molecular mechanisms regulating hematopoiesis and leukemogenesis.

Dr. Judith Marsh will review the current results of immunosuppressive therapy (IST) and bone marrow transplantation (BMT) in adult patients with aplastic anaemia, discussing reasons for the improvement in outcome with time. Distinguishing acquired aplastic anemia from the inherited bone marrow failure syndromes is vital and straightforward in most cases. The finding of telomerase gene mutations in some adult patients with apparent acquired aplastic anemia will also impact on therapeutic planning, since a lack of response to IST typifies such patients. Critical barriers to successful outcome after allogeneic BMT will be discussed, and the management of patients with acquired aplastic anemia who have no HLA-compatible donor and who fail to respond to IST will be reviewed. Because overall survival is similar between IST and BMT, the need for comparative quality-of-life studies in future treatment strategies for BMT and IST will be emphasized.

Acute Promyelocytic Leukemia

Chair:

Bob Löwenberg, MD, PhD, Erasmus University Medical Center, Rotterdam, The Netherlands

Speakers:

Francesco Lo-Coco, MD, University Tor Vergata, Rome, Italy
The Biology of Acute Promyelocytic Leukemia

Miguel A. Sanz, MD, PhD, University Hospital La Fe, Valencia, Spain
Current Treatment of Acute Promyelocytic Leukemia

Raul C. Ribeiro, MD, St. Jude Children’s Research Hospital, Memphis, TN
The International APL Protocol: A Model for Collaborative Clinical Research in Developing Countries

Acute promyelocytic leukemia (APL) represents a molecularly defined entity of acute myeloid leukemia (AML) with unique diagnostic and therapeutic requirements. The pathobiology of APL serves as a role model for transcriptional deregulation as a central mechanism in leukemogenesis. It has provided insights that are directly relevant to developmental diagnostics and therapeutics in this disease. The disease is more prevalent in certain geographic areas. The therapeutic approach to the patient with APL has evolved to one that is based upon an increasing arsenal of therapeutic options applied on a more and more rationalized and individualized basis. This session will highlight recent advances in our understanding that are directly relevant to the treatment algorithm in patients with APL.

Dr. Francesco Lo-Coco will review the molecular pathobiology of APL. He will also discuss how the genetic and biologic features of APL impact diagnostic distinctions as a basis of tailored treatment, and he will discuss the clinical utility of molecular monitoring of residual disease throughout treatment.

Dr. Miguel Sanz will review the treatment options for this highly curable subtype of acute leukemia, which still has particular subsets of patients failing. His presentation will highlight management issues commonly encountered in clinical practice and will include a review of recent results of large multicenter studies using various combinations of retinoic acid and anthracycline-based chemotherapy as well as the current role of stem cell transplantation. Dr. Sanz will also discuss the place of the newer agents in front-line therapy, which include arsenicals and gemtuzumab ozogamicin, and subsequently he will discuss the therapeutic approach in the patient following relapse.

Dr. Raul Ribeiro will describe the clinical epidemiology of APL in selected developing countries and also describe the most common causes of treatment failures in patients with APL in these countries. Finally, he will present the efforts of the International Members Committee of the American Society of Hematology to transfer the implementation of an effective treatment regimen and uniform supportive care guidelines to institutions in Brazil, Mexico, and Jordan.

Myelodysplastic Syndromes

Chair:

Stephen D. Nimer, MD, Memorial Sloan-Kettering Cancer Center, New York, NY

Speakers:

Pierre Fenaux, MD, Hôpital Avicenne, Université Paris, Bobigny, France
Therapy of the 5q-Syndrome

James W. Vardiman, MD, University of Chicago, Chicago, IL
Myelodysplastic Syndromes: Hematopathologic Concepts and Controversies

Charles A. Schiffer, MD, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI
A Practical Case-Based Approach to Myelodysplastic Syndromes

Within the past two years, two therapies have been approved by the FDA for the treatment of patients with myelodyplastic syndromes (MDS). Thus, this is an opportune time to better understand the biological basis of these disorders and the basis for the variable response to therapeutic inventions. These disorders are not only heterogeneous pathologically, but they vary greatly in their clinical presentation. The goals of this Education Session are to discuss areas of controversy in the pathologic diagnosis and classification of the myelodysplastic syndromes and guidelines for their treatment, including several specific clinical syndromes.

The clonal hematopoietic cells that characterize the myelodysplastic syndromes commonly have cytogenetic abnormalities, such as 5q-, 7q-, or 20q-. Perhaps 10 percent of MDS patients may have the 5q-syndrome (which can be defined using diagnostic criteria from the World Health Organization), whereas other MDS patients may not have this syndrome but may have a 5q-abnormality, either alone or in conjunction with other cytogenetic abnormalities. Yet, the 5q-abnormality is also seen in patients with AML. This session will include a discussion of the clinical features of MDS with an interstitial deletion of chromosome 5q and cover new developments in its treatment, such as the drug lenalidomide, which was FDA approved for treating lower-risk, transfusion-dependent patients with 5q-MDS.

Other presentations will focus more broadly on the pathologic and cytogenetic evaluation of MDS and on therapeutic approaches to these diseases. Several challenging cases will be presented to demonstrate how the classification and prognostic factor scoring systems influence the development of guidelines for the proper management of MDS patients. Because the diagnosis of myelodysplasia may rest on the subjective finding of dysplasia within the hematopoietic cells in the bone marrow, this session will provide objective insights into these disorders, which represent an important take-off point for studying the processes that underlie bone marrow failure and the progression toward acute leukemia.

Chronic Myeloid Leukemia

Chair:

Armand Keating, MD, Princess Margaret Hospital, Toronto, Ontario, Canada

Speakers:

Timothy Hughes, MD, MBBS, Institute of Medicine and Veterinary Science, Adelaide, Australia ABL Kinase Inhibitor Therapy for CML: Baseline Assessments and Response Monitoring

Michael J. Mauro, MD, Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR
Defining and Managing Imatinib Failure and Suboptimal Response

Jane F. Apperley, MBChB, Hammersmith Hospital, Imperial College School of Medicine, London, United Kingdom
Managing the CML Patient Through and After Transplantation

The management of chronic myeloid leukemia (CML) continues to undergo refinement with new developments in monitoring disease burden, assays for detecting Abl kinase mutations, the management of sub-optimal responses with imatinib, and the treatment of imatinib-resistant disease with new agents. In addition, the selection of patients undergoing allogeneic transplantation and their management after transplant needs to be considered in the context of recent developments.

Dr. Timothy Hughes will discuss the baseline assessments that are currently indicated for CML patients to determine the appropriate initial management and review newer assays that appear promising, but require further confirmation regarding their prognostic value. The optimal monitoring strategy to adopt for patients receiving imatinib therapy will also be discussed. Evidence supporting the value of regular, accurate, and reliable RQ-PCR assays will be reviewed. While RQ-PCR monitoring has many theoretical advantages as a primary monitoring strategy, its widespread use has been limited by the lack of access and lack of standardization between laboratories. Recent progress towards harmonization of the assay between laboratories and the adoption of an International Scale for BCR-ABL values will be summarized. Dr. Hughes will also cover the indications for cytogenetic studies and mutation screening.

Dr. Michael Mauro will discuss the key time points and thresholds of response during therapy with imatinib that are achieved or not, to help guide identification of the patient with suboptimal response or failure of therapy. Decision-making regarding changes in therapy will also be addressed and will include a review of pre-therapy risk, response to and tolerance of imatinib, feasibility of alternative therapies, and, in the case of clinical resistance, the data clarifying the underlying cause for resistance. The central role of Bcr-Abl kinase domain mutations in resistance to imatinib will be considered in the context of increasing availability of molecular testing for such mutations and the rapid development and studies of alternative Abl kinase inhibitors, in particular nilotinib and dasatinib, as well as other compounds. Dr. Mauro will also discuss the natural history of CML suboptimally responding or failing to respond to imatinib as well as review the influence of improved and novel molecular studies, complementary strategies to reduce or eliminate residual disease, alternative inhibitors of Bcr-Abl, and the continued availability and improved outcomes with stem cell transplant.

Dr. Jane Apperley will discuss the selection of patients for allotransplantation and review the role of reduced intensity versus myeloablative regimens. The effect of the use of imatinib pre-transplant will be evaluated, as will the frequency and interpretation of monitoring after transplant. The management of relapse with kinase inhibitors versus donor lymphocyte infusions will also be discussed, and the options for imatinib and transplant failures will be reviewed. Finally, Dr. Apperley will assess the utility of transplanting patients with advanced disease.

Myeloproliferative Disorders

Chair:

D. Gary Gilliland, MD, PhD, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA

Speakers:

Ross Levine, MD, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
The Role of JAK-STAT Signaling in the Pathogenesis of Myeloproliferative Disorders

Ayalew Tefferi, MD, Mayo Clinic, Rochester, MN
Clinical Practice in Myeloproliferative Disorders in the JAK2V617F Era

Tiziano Barbui, MD, Ospedali Riuniti di Bergamo, Bergamo, Italy
Myeloproliferative Disorders in Pregnancy and Other Management Issues

This session will focus on recent advances in our understanding of the molecular pathophysiology and treatment of myeloproliferative (MPD) diseases. Topics covered will include an overview of the molecular genetics of MPD, with a focus on the role of JAK2 mutations in polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IMF). Current strategies for clinical prognostication and therapeutic strategies in PV, ET, and IMF will be discussed. The approach to management of myeloproliferative diseases in pregnancy will be reviewed as well as the management of complications of MPD, including thrombosis and hemorrhage.

Dr. Ross Levine will summarize our current understanding of the role of JAK-STAT pathway activation in the pathogenesis of PV, ET, and myelofibrosis with myeloid metaplasia (MMM). The role of the constitutively active JAK2V617F kinase in the pathogenesis of these disorders will be discussed as well as new mutations in patients with MPD that activate the JAK-STAT signal transduction pathway. Experimental data that support a role for small molecule inhibitors of JAK-STAT signaling in therapy of PV, ET, and idiopathic myelofibrosis (IMF) will be reviewed.

Dr. Ayalew Tefferi will discuss the impact of the JAK2V617F discovery on the classification of myeloproliferative disorders as well as diagnosis, prognostication, and treatment of patients with polycythemia vera, essential thrombocythemia, and myelofibrosis. He will then summarize the information in diagnostic and treatment algorithms that are applicable in routine clinical practice.

Dr. Tiziano Barbui will discuss specific clinical management issues in patients with MPD, including the management of MPD in pregnancy. Strategies for diagnosis and treatment of thrombosis and hemorrhage in MPD will also be discussed.

Chronic Lymphocyte Leukemia

Chair:

Thomas J. Kipps, MD, PhD, University of California, San Diego, CA

Speakers:

Nicholas Chiorazzi, MD, The Feinstein Institute for Medical Research, Manhasset, NY
Biology of CLL

Emili Montserrat, MD, Hospital Clinic, Barcelona, Spain
New Prognostic Markers in CLL

William G. Wierda, MD, PhD, The University of Texas M.D. Anderson Cancer Center, Houston, TX
Current and Investigational Therapies for CLL

There have been exciting developments in our understanding of the biology and treatment of chronic lymphocytic leukemia (CLL). This session will cover these developments and provide for discussion of the state of the art and future therapies for this disease.

Dr. Nicholas Chiorazzi will review studies that are changing our concepts of this disease. Once considered “an accumulative disease of immunolgically incompetent lymphocytes,” recent studies have revealed CLL to be a much more dynamic process. Indeed, some patients with apparently stable disease actually may have leukemia cells that have a relatively high rate of proliferation that appears counter-balanced by cell turnover. In addition, insight into the biology of this disease has provided clues regarding the factors that may be responsible for leukemia-cell proliferation and/or cell-turnover, as well as markers that can help distinguish between patients who may have indolent versus aggressive disease.

Dr. Emili Montserrat will review our current understanding of markers that can distinguish indolent versus relatively aggressive disease. Validation of the relative strength of these prognostic markers in predicting disease outcome is allowing for a risk-based stratification of patients that soon may be incorporated into novel treatment algorithms, including those involving non-myeloablative allogeneic stem cell transplantation.

Dr. William Wierda will review current and evolving treatments for this disease. The advent of passive immune therapy for patients with this disease has been associated with significant improvements in survival, ushering in the use of “chemo-immunotherapy” as front-line and salvage therapy. Metabolic pathways have been identified that appear distinctive for the leukemia cell, providing insight into use of novel agents that could be used to treat CLL more selectively than standard chemotherapy. Finally, clinical trials of vaccine strategies, using either recombinant idiotype protein vaccines or whole-cell vaccines modified via gene transfer, may allow for development of clinically effective host anti-leukemia immunity, similar in some respects to the graft-versus-leukemia effects noted for some patients following allogeneic stem cell transplantation.

Anti-Thrombotic Therapy: Problems and Issues

Chair:

Charles S. Abrams, MD, University of Pennsylvania, Philadelphia, PA

Speakers:

Lawrence L. Leung, MD, VA Palo Alto Health Care System, Stanford University School of Medicine, Palo Alto, CA
Perioperative Management of High-Risk Patients

William H. Geerts, MD, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Preventing Venous Thromboembolism in High-Risk Patients

Brian F. Gage, MD, Washington University Medical School, St. Louis, MO
Pharmacogenetics of Coumarins

Anti-thrombotic therapy in hospitalized patients can be fraught with hemorrhagic sequelae. The objective of this session will be to discuss common but difficult coagulation issues faced by consultative hematologists.

Dr. Laurence Leung will review common coagulation issues in perioperative patients. Hematologists are frequently asked to assess the risk of bleeding or thrombosis in these patients, and are often relied upon to interpret the operative risk of patients with prolonged prothrombin and activated partial thromboplastin time. Dr. Leung will speak on the appropriate evaluation of abnormal coagulation tests in pre-operative and post-operative patients, determination of operative risk, and the approach to the patient with post-operative bleeding.

Dr. William Geerts will discuss difficult issues related to the prevention and treatment of thrombotic diseases in high-risk patients. Intensive-care-unit patients, as well as patients who have had recent major trauma, spinal cord, or brain injuries, are simultaneously at high risk for both thromboembolic disease and hemorrhage. Dr. Geerts will discuss risks and benefits of anticoagulation and fibrinolytic therapy in these high-risk patients. He will also discuss the appropriate indications for mechanical devices, such as inferior vena cava filters in patients at high risk for thrombosis.

Dr. Brian Gage will explain the recent advances in the pharmacogenomics of anticoagulation therapy. Determination of the correct warfarin dosage remains problematic. Over the past few years, polymorphisms of several genes have been found to contribute to the sensitivity of some patients to warfarin. Genetic variations in the hepatic cytochrome P450 2C9 (CYP2C9) isoenzyme that inactivates warfarin contributes to some of the seeming unpredictability in warfarin sensitivity. Gene polymophisms in the gene encoding vitamin K epoxide reductase complex 1 (VKORC1) can also affect the patient’s response to warfarin. Dr. Gage will present retrospective and prospective data that demonstrates the importance of these genetic polymorphisms in warfarin therapy. He will also comment on the implications of these genetic variations on clinical practice.

Bleeding Disorders

Chair:

Donna DiMichele, MD, New York Presbyterian Hospital, Weill Cornell Center, New York, NY

Speakers:

David Lillicrap, MD, Queen’s University, Kingston, Ontario, Canada
The Role of Immunomodulation in the Approach to Factor VIII Inhibitors

W. Keith Hoots, MD, The University of Texas M.D. Anderson Cancer Center and Health Science Center and the Gulf States Hemophilia and Thrombophilia Center, Houston, TX
Challenges in the Therapeutic Use of a “So-Called” Universal Hemostatic Agent: Recombinant Factor VIIa

Alice D. Ma, MD, Harold R. Roberts Comprehensive Hemophilia Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
Acquired Factor VIII Inhibitors: Pathophysiology and Treatment

The hemostatic management of severe life- or limb-threatening bleeding can pose a significant therapeutic challenge for the hematologist. Such bleeding emergencies are frequently encountered in children and adults with severe congenital hemophilia who develop anti-factor VIII or IX inhibiting antibodies; in patients with major intracranial hemorrhage, trauma-related bleeding, or bone marrow failure with or without an acquired coagulopathy; and in individuals with the abrupt onset of acquired hemophilia A. This education session will focus on both state-of-the-art and emerging therapeutic approaches to each of these problems.

Dr. David Lillicrap will review the mechanisms underlying the development of factor VIII inhibitors and the role of immunomodulation in the clinical management of this complication. Approximately 25 percent of hemophilia A patients develop factor VIII inhibitors, and this presentation will address the various pathogenetic factors that contribute to this propensity. The clinical management of patients with inhibitors involves two main strategies, the use of hemostatic agents that can prevent or treat bleeding in spite of the inhibition of factor VIII co-factor activity and the induction of immunologic tolerance to factor VIII. This presentation will review current and potential future approaches to immune tolerance induction with reference to the ways in which these strategies might alter the balance from a productive to a tolerogenic immune response.

Dr. Keith Hoots will review the results of clinical trials focused on the non-hemophilia uses of activated recombinant factor VIIa (rFVIIa), including intra-cranial hemorrhage, bone marrow transplant, pulmonary hemorrhage, and obstetrical trauma. These results will be discussed in the context of what is now known about the tissue factor-dependent use of rFVIIa in hemophilia as well as the tissue factor-independent activity of higher dosing. The thrombotic adverse event profile for each of these clinical uses will be discussed in detail and compared to that for factor VII deficiency and hemophilia inhibitors, licensed treatment indications for rFVIIa. Specific recommendations will be presented concerning the need for and proposed nature of coagulation testing that should precede all off-label use. Finally, institutional experience with “gatekeeper” monitoring of rFVIIa off-label use, including outcomes and adverse events, will also be reviewed.

Dr. Alice Ma will review acquired inhibitors to factor VIII. An update on the pathophysiology of these inhibitors will be provided, and their clinical features and diagnostic evaluation will be discussed. The safety and efficacy of novel therapeutic options will also be examined, including rituximab for antibody eradication and recombinant activated factor VII for the treatment of inhibitor-related bleeding.

Molecular Pharmacogenomics

Chair:

James Downing, MD, St. Jude Children’s Research Hospital, Memphis, TN

Speakers:

Stella M. Davies, MBBS, PhD, Cincinnati Children’s Hospital and Medical Center, Cincinnati, OH
Pharmacogenomics and Cancer Therapy

James Downing, MD, St. Jude Children’s Research Hospital, Memphis, TN
Tumor-Specific Genetic Lesions and Their Influence on Therapy

Garry P. Nolan, PhD, Stanford University School of Medicine, Palo Alto, CA
Profiling Signaling Pathways at the Single Cell Level: Implications for Therapy

Pharmacogenomics has traditionally focused on the identification of inherited genetic differences that influence a patient’s response to a specific therapeutic agent. These differences can range from inherited variability in the genes affecting drug absorption, distribution, intracellular transport, metabolism, and elimination, to variability in the genes that encode either the target of the drug or components of the pathway affected by the drug. Understanding how these variations, either individually or collectively, influence a patient’s response to therapy constitutes the major questions pursued in the field. In addition, the genetic differences inherent within cancer cells constitute the other major variable in a patient’s ultimate response to therapy. In this session, recent advance made in the applications of molecular pharmacogenomic principles to the treatment of hematopoietic malignancies will be presented. The presenters will also describe the development of new methodologies that will help to better understand the differences in the molecular pathophysiology of cancer cells that affect their response to therapeutic agents.

Dr. Stella Davies will present an overview of the recent advances in pharmacogenomics, including how these advances affect therapeutic decisions and how some findings may provide insights into a patient’s predispositions to developing cancer.

Dr. James Downing will provide an overview of high-throughput genomics methods that are used to identify genetic lesions within cancer cells. Moreover, he will explore how differences in the collection of somatically acquired genetic lesions within cancer cells can profoundly influence their response to chemotherapy.

Dr. Garry Nolan will provide a description of the application of single-cell signal pathway analysis and its implication for assessing therapeutic effects and modern protocol design.

Supportive Care of Infections in Patients with Hematologic Malignancies

Chair:

John R. Wingard, MD, University of Florida College of Medicine, Gainesville, FL

Speakers:

Eric J. Bow, MD, University of Manitoba, Winnipeg, Manitoba, Canada
Of Yeasts and Hyphae: Medical Mycology for the Hematologist

James C. Wade, MD, MPH, Medical College of Wisconsin, Milwaukee, WI
Viral Infections in Patients with Hematologic Malignancies

David R. Nelson, MD, University of Florida College of Medicine, Gainesville, FL
Viral Hepatitis: Manifestations and Management Stategies

Infections are serious complications of the treatment of hematologic malignancies due to compromises in host defenses both from the underlying disease and its treatment. Infections not only pose life-threatening risks, but they also may necessitate alteration of anti-neoplastic treatment approaches.

Dr. Eric Bow will review the changing epidemiology of and risk factors for invasive fungal infections in patients with hematological malignancies as a function of innovations in the management of hematologic cancers as well as changes in antimicrobial prescribing practices. He will provide a review of various antifungal agents and describe the spectrum of treatment strategies ranging from prophylaxis, presumptive, and empirical therapy to treatment of documented invasive fungal infection.

Dr. James Wade will discuss the various viral infections that occur in patients with hematologic malignancies. He will describe the clinical manifestations of and risk factors for the herpes viruses and respiratory viruses. He will review what treatment options exist and strategies to mitigate their sequelae.

Dr. David Nelson will provide a review of the various viral hepatitis agents, mechanisms of reactivation, and clinical manifestations. He will discuss management strategies to minimize acute and chronic morbidity.

Acute Myeloid Leukemia

Chair:

Hillard M. Lazarus, MD, Case Comprehensive Cancer Center, Case Western Reserve University and Ireland Cancer Center, University Hospitals of Cleveland, Cleveland, OH

Speakers:

Clara D. Bloomfeld, MD, The Ohio State University Comprehensive Cancer Center and the Arthur G. James Cancer Hospital and Solove Research Institute, Columbus, OH
Gene Expression and Mutation and Prognosis in Acute Myeloid Leukemia

Donald Small, MD, PhD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, Baltimore, MD
FLT3 in Acute Myelogenous Leukemia: Biology and Treatment

Wendy Stock, MD, University of Chicago, Chicago, IL
Controversies in Treatment of Acute Myeloid Leukemia: A Case-Based Discussion

Acute myeloid leukemia (AML) represents a disease that formerly was uniformly fatal. Because of painstaking laboratory and clinical investigations, the vast majority of affected patients now attain considerable benefit as a result of newer diagnostic testing and therapeutic intervention, and many patients are cured of this malady. Investigators and practitioners continue to focus on identifying the biologic behavior of this heterogeneous disease using sophisticated testing in order to improve upon available therapies and develop new treatment approaches. This session will focus on several of these efforts.

Dr. Clara Bloomfield will discuss the prognostic significance of gene expression and mutation in adult AML. Molecular dissection of the 40-45 percent of AML patients with normal cytogenetics at diagnosis has shown that mutations or expression levels in a number of genes have prognostic significance, as does gene expression profiling. Molecular dissection of the core-binding factor leukemias is also identifying prognostic significance of specific genetic mutations and expression profiling. While this session will focus on these two areas, the prognostic significance of selected specific gene mutations (such as RAS) and genetic profiling of AML globally will be presented where definitive data exist.

Dr. Donald Small will speak about the role of FLT3 mutations in AML. Participants should learn about the different types of FLT3 mutations as well as their incidence and prognostic significance in adult and pediatric AML. The signaling pathways by which FLT3 mutations contribute to alterations in myeloid biology will be discussed. Finally, the audience will hear about the development of drugs to molecularly target FLT3 as a new therapeutic in the fight against AML.

Dr. Wendy Stock will use case-based presentations to highlight current controversies and potential advances in the treatment of two very challenging populations: AML in the elderly and therapy-related AML (t-AML). Assessment of disease biology and co-morbid conditions may now, more than ever before, guide the choice of therapy for these challenging patients. Discussion will focus on novel epigenetic and immunologic experimental approaches that will move the field beyond standard induction chemotherapy for older AML patients or myeloablative allogeneic transplant for patients with t-AML.

Thrombocytopenia

Chair:

James N. George, MD, University of Oklahoma Health Sciences Center, Oklahoma City, OK

Speakers:

Diana S. Beardsley, MD, PhD, Yale University School of Medicine, New Haven, CT
ITP in the 21st Century

Theodore E. Warkentin, MD, McMaster University, Hamilton, Ontario, Canada
Think of HIT

J. Evan Sadler, MD, PhD, Washington University School of Medicine, Howard Hughes Medical Institute, St. Louis, MO
Thrombotic Thrombocytopenic Purpura: A Moving Target

Disorders of thrombocytopenia are common problems, often with difficult evaluation and management problems. This session will cover current knowledge on pathogenesis, evaluation, and management of three of the most important disorders: immune thrombocytopenic purpura (ITP), heparin-induced thrombocytopenia (HIT), and thrombotic thrombocytopenic purpura (TTP).

Dr. Diana Beardsley will describe the current understanding of the mechanisms of thrombocytopenia in ITP. Immune-mediated platelet destruction has been considered to be the most prominent cause of thrombocytopenia, but diminished – or less than optimal – platelet production may also be important. Understanding the mechanism of thrombocytopenia is important for understanding different management options. Anti-CD20 is increasingly used in both children and adults; what is the current best practice for anti-CD20 treatment in ITP? Recent clinical trials have documented that thrombopoietic agents can increase platelet counts in patients with ITP. What is their potential role in the management of these patients?

Dr. Theodore Warkentin will address the continuing complex problems surrounding heparin-induced thrombocytopenia (HIT). This disorder can present in many ways, ranging from common complications, such as isolated thrombocytopenia, venous thromboembolism, or acute limb ischemia, to less common but specific presentations, including skin lesions at the heparin injection site, post-bolus acute systemic reactions, and hemorrhagic necrosis of the adrenal glands. HIT that begins after stopping heparin treatment is increasingly recognized. Since timely diagnosis and treatment may reduce the frequency of bad outcomes, this presentation will focus on clinical circumstances that should prompt the clinician to “think of it.”

Dr. Evan Sadler will describe the remarkable progress in understanding the pathophysiology of TTP. Most patients with idiopathic TTP have acquired autoantibody inhibitors of ADAMTS13, a plasma protease that normally cleaves von Willebrand factor within platelet-rich thrombi and thereby limits thrombus growth. Since severe deficiency of ADAMTS13 identifies a specific mechanism of TTP, measurements of plasma ADAMTS13 and the anti-ADAMTS13 antibody titer may be useful biomarkers of disease. Thrombotic microangiopathy that is not associated with a measurable deficiency of ADAMTS13 may have a different etiology and may benefit from interventions other than plasma exchange. Two important clinical questions will be addressed. First, by emphasizing TTP caused by ADAMTS13 deficiency, are we in danger of neglecting other causes that should be treated with plasma exchange? Second, should we treat apparently asymptomatic patients who have severe ADAMTS13 deficiency to prevent future disease, and, if so, how?

Updates in Transfusion Medicine: DLI, Platelets, and TRALI

(This session is jointly sponsored with AABB.)

Chair:

Christopher D. Hillyer, MD, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA

Speakers:

John D. Roback, MD, PhD, Emory University School of Medicine, Atlanta, GA
Vaccine Enhanced DLI

Richard M. Kaufman, MD, Brigham and Women’s Hospital, Harvard University School of Medicine, Boston, MA
Platelets – Testing, Dosing, and the Storage Lesion: Recent Advances

Darrell J. Triulzi, MD, Institute for Transfusion Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
TRALI: Current Understanding and Future Directions

Historically, “blood banking” was the term commonly employed to describe the collection of blood from human donors for the purposes of transfusion and its manufacture, processing, and storage. With technical advances in the “blood bank” ranging from component compatibility testing to irradiation and leukoreduction, newer terms have evolved, including “transfusion medicine,” notably used to describe the provision of optimal and specific care to often complex and specialized patients. Then, the broader and more commonplace use of blood-, marrow-, and tissue-derived therapeutic cellular components and the focus on good manufacturing and laboratory processes and quality systems often made the blood bank or transfusion medicine service a logical choice for the collection, processing, and storage of what is now being referred to as “HCT/P,” or “human cells, tissues, and cellular- and tissue-based products.” Finally, hematologists and transfusion medicine physicians often provide consultation and component therapy from what are often called “related biological therapies,” which include blood-derived and recombinant proteins, such as albumin, IvIg, ATIII, FVIII, and more recently, FVIIa. Though the boundaries of the field of transfusion medicine are clearly both expanding and not as yet well-defined, this term, from a practical perspective, can be used to cover all of the elements listed above.

In this session, three important and emerging areas in transfusion medicine will be examined in detail.

Dr. John Roback will discuss the use of vaccine-enhanced donor lymphocyte infusions (DLI) as a novel way to deliver immunotherapy to immunocompromised individuals for protection against opportunistic infections, including CMV post-HSCT.

Dr. Richard Kaufman will explore advances in the understanding of the biological basis of the platelet storage lesion, platelet cryopreservation, and the residual risk of bacterial contamination and its mitigation in platelet components for transfusion.

Lastly, Dr. Darrell Triulzi will discuss our current understanding of the pathophysiology of transfusion-related acute lung injury (TRALI) and potential ways to abrogate this serious hazard of transfusion.

Hodgkin Lymphoma

Chair:

Ralph M. Meyer, MD, National Cancer Institute of Canada Clinical Trials Group, Queens University, Kingston, Ontario, Canada

Speakers:

Mary Gospodarowicz, MD, FRCPC, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada
Management of Patients with Limited-Stage Hodgkin Lymphoma

Malik E. Juweid, MD, University of Iowa College of Medicine, Iowa City, IA
The Utility of PET Scanning in Managing Patients with Hodgkin Lymphoma

Andreas Engert, MD, University Hospital of Cologne, Koln, Germany
Biology, Clinical Course, and Management of Nodular Lymphocyte Predominant Hodgkin Lymphoma

As opportunities for long-term outcomes continue to increase for patients with Hodgkin lymphoma, evolving priority topics include selection of treatments that will maintain curative potential and reduce risks of late toxicities, optimum incorporation of new imaging technologies into practice, and management of patients with distinct disease subtypes.

Dr. Mary Gospodarowicz will review recent trials comparing treatment alternatives in patients with limited-stage classical Hodgkin lymphoma. These patients exemplify the attention that must be paid to risks of long-term late effects, in addition to traditional aspects of disease control. Current debate regarding the specifics of radiation therapy, the role of chemotherapy as a single modality, and the concept of response-adapted therapy will be reviewed.

Dr. Malik Juweid will discuss the evolving role of positron emission tomographic (PET) scanning with and without CT scanning in the management of patients with Hodgkin and non-Hodgkin lymphoma. Topics will include the role of this technology in pre-treatment staging, determination of prognosis during therapy, and of response post-therapy. New classification schemes of response assessment that incorporate PET scanning criteria will be reviewed.

Dr. Andreas Engert will discuss nodular lymphocyte predominant Hodgkin lymphoma and will review the biologic and clinical rationale for considering this disorder as a distinct entity separate from classical Hodgkin lymphoma. Aspects of the clinical course, including optimum management strategies, will be presented.

Non-Hodgkin Lymphoma

Chair:

Jane N. Winter, MD, Northwestern University, Chicago, IL

Speakers:

Laurie Sehn, MD, MPH, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
Optimal Use of Prognostic Markers in Non-Hodgkin Lymphoma

Myron S. Czuczman, MD, Roswell Park Cancer Institute, Buffalo, NY
Current Controversies in Treatment of Follicular Lymphoma

Lisa DeAngelis, MD, Memorial Sloan-Kettering Cancer Center, New York, NY
Advances in the Treatment of Central Nervous System Lymphoma

More than ever, the heterogeneity of the non-Hodgkin lymphomas is apparent. We are challenged to understand its complex and diverse pathobiology and to translate the newest developments into clinical advances to benefit our patients.

Dr. Laurie Sehn will provide a critical update on prognostic markers in the non-Hodgkin Lymphoma and help to integrate our evolving knowledge of biomarkers and gene expression patterns into clinical practice.

Dr. Myron Czuczman will address the many controversies in the treatment of follicular lymphomas. When to treat, how to choose among therapies, and how to combine or sequence treatments will be some of the issues discussed.

Dr. Lisa DeAngelis will review the state of the art in the treatment of central nervous system lymphomas. Her presentation will include discussion of the appropriate role for radiation therapy and associated toxicities.

Multiple Myeloma

Chair:

Philip R. Greipp, MD, Mayo Clinic, Rochester, MN

Speakers:

Robert Z. Orlowski, MD, PhD, University of North Carolina at Chapel Hill, Chapel Hill, NC
Treating Patients Who Are Not Candidates for Transplant

Jeffrey Zonder, MD, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI
Thrombotic Complications of Myeloma Therapy

Bhoomi Mehrotra, MD, Long Island Jewish Medical Center, New Hyde Park, NY
Bisphosphonate Complications Including Osteonecrosis of the Jaw

Despite unprecedented progress in the development of new agents and advances in transplant for the treatment of multiple myeloma (MM), a predictably curative regimen remains to be found for this remitting, relapsing disease. Often the disease or its therapy may be chronic and debilitating. After an appropriate induction regimen including dexamethasone and thalidomide, or likely in the near future revlimid and dexamethasone, transplant produces complete response in one-third or more of patients. The gap between the effectiveness of transplant regimens and newer combinations seems to be narrowing. The role of transplant in myeloma will be discussed at other sessions.

For practice today, we increasingly rely on evidence-based or consensus-based best-practice guidelines that answer essential questions about the treatment of the non-transplant candidate or the patient who wishes to defer transplant:

For patients who are not candidates for early transplant: Is melphalan, prednisone, and thalidomide (MPT) the best regimen for newly diagnosed patients?
Will MPT be replaced by melphalan, prednisone, and revlimid (MPR) or a similar regimen? What other combinations offer promise?
Will new regimens replace transplant or will they enhance it? How important is high dose dexamethasone?
How should high-risk patients be defined? Should they be treated differently?
How much do new regimens, especially those which include thalidomide or revlimid and dexamethasone, increase the risk of thromboembolism complications? What should be done to minimize the risks of thromboembolism?
Based on existing evidence of the risks of renal insufficiency and osteonecrosis of the jaw (ONJ) as well as the perceived benefits of bisphosphonate therapy, what is the current best practice with regard to the use of pamidronate or zoledronic acid or other bisphosphonates?

Myeloma therapy requires the effective management not only of consequences of disease but also complications of treatment. Therapy that is evidence-based or consensus-driven is needed to reliably improve quality of life and outcome and to help us better understand how to approach such questions in this all-too-often fatal disease.

Hemolytic Anemia

Chair:

Edward J. Benz, Jr., MD, Dana-Farber Cancer Institute, Boston, MA

Speakers:

Philip C. Hoffman, MD, University of Chicago, Chicago, IL
Autoimmune Hemolytic Anemia

Morie A. Gertz, MD, Mayo Clinic, Rochester, MN
Cold Hemolytic Disorders

Robert A. Brodsky, MD, Johns Hopkins University School of Medicine, Baltimore, MD
New Insights into Paroxysmal Nocturnal Hemoglobinuria (PNH)

Dr. Philip Hoffman will review current concepts regarding the incidence and epidemiology of autoimmune hemolytic anemia (AIHA), including recent data associating AIHA with pyrimidine analogues and with bone marrow or solid organ transplantation. He will also provide an update on the mechanisms of red cell destruction. Thromboembolic complications of AIHA will be discussed briefly. Information on newer therapeutic options, including monoclonal antibody therapy, will be emphasized.

Dr. Morie Gertz will provide an overview of hemolytic anemia associated with cold reactive antibodies. Paroxysmal cold hemoglobinuria will be reviewed. Cold hemagglutinin disorders, including the polyclonal form in children, as well as the more ominous and treatment-resistant cold agglutinin disorders of adults, will be reviewed. Recent data on the association of the latter with low-grade lymphomas and Waldenström’s macroglobulinemia will be covered. New therapeutic interventions using monoclonal antibody therapy reported over the past 36 months will be covered. This presentation will be patient- and case-based. The clinical features of both syndromes and how to avoid overlooking the diagnosis will be covered.

Dr. Robert Brodsky will review the clinical presentation and laboratory methods available to diagnose paroxysmal nocturnal hemoglobinuria. The pathophysiology of the disease and the relevance of PIG-A mutations in health and disease will be discussed. Finally, rational therapies for paroxysmal nocturnal hemoglobinuria based on drugs that inhibit the terminal component of the complement cascade will also be discussed.

T-Cell Lymphoma

Chair:

Steven T. Rosen, MD, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL

Speakers:

Elaine S. Jaffe, MD, National Cancer Institute, National Institutes of Health, Bethesda, MD
Pathobiology of T-Cell Lymphomas

Steven T. Rosen, MD, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
Therapy of Cutaneous T-Cell Lymphomas

John P. Greer, MD, Vanderbilt University Medical Center, Nashville, TN
Therapy for Peripheral T-Cell/Natural Killer Neoplasms

T-cell non-Hodgkin lymphomas represent a spectrum of malignancies with distinct clinico-pathologic features. These disorders represent approximately 10-20 percent of the non-Hodgkin lymphomas with varying incidence rates noted in different geographic locations.

Dr. Elaine Jaffe will review the pathologic features characteristic of each entity. She will discuss the histologic, immunologic, and molecular alterations that are associated with the most common subtypes, emphasizing pathobiological features that influence clinical presentation and outcome.

Dr. Steven Rosen will discuss the cutaneous T-cell lymphomas. He will highlight the clinical presentation, prognostic features, and therapeutic approaches used to treat these diseases. His presentation will focus on mycosis fungoides, Sezary syndrome, lymphomatoid papulosis, and primary cutaneous anaplastic large-cell lymphoma.

Dr. John Greer will present an overview of the systemic T-cell lymphomas. He will discuss the current treatment strategies utilized for peripheral T-cell lymphoma, anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, and peripheral T-cell leukemias.

Reduced-Intensity Allo BMT

Chair:

Claudio Anasetti, MD, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

Speakers:

Brenda M. Sandmaier, MD, Fred Hutchinson Cancer Research Center, Seattle, WA
Outcomes with Myeloid Malignancies

Issa F. Khouri, MD, The University of Texas M.D. Anderson Cancer Center, Houston, TX
The Role of Reduced-Intensity Allotransplants for Lymphoma

Franco Locatelli, MD, University of Pavia, Pavia, Italy
Hemoglobinopathies

Engraftment of hematopoietic cells from closely HLA-matched donors can occur without recipient marrow ablation. Potent and selective immune suppressive drugs or low dose irradiation can facilitate donor hematopoietic and immune reconstitution and eradicate certain malignancies, with less toxicity and early mortality than historical regimes. This educational session will review transplant outcome data after the spectrum of reduced intensity regimes, and show which regimes are powerful enough to achieve donor engraftment and long-term relapse-free survival in myeloid malignancies and lymphoma, and which regimes are safe and effective for engraftment of highly sensitized patients with non-malignant disorders, including hemoglobinopathies.

Dr. Brenda Sandmaier will first introduce the principles of transplantation immunology that justify the use of reduced intensity regimes. Acute myeloid leukemias and myelodysplastic syndromes present the challenge of a large tumor bulk in most patients: the speaker will discuss how much disease burden is tolerable at the time of transplantation, when cytoreduction is indicated before referral for transplant, and what regimes have been associated with the best outcome. Patients with chronic myeloid leukemia are usually imatinib-refractory at referral, yet naïve to chemotherapy so that they have a large tumor burden and are at high risk for engraftment failure: the speaker will review the recent experience with reduced intensity regimes in these patients.

Dr. Issa Khouri will first discuss the indications for hematopoietic cell allografts versus autografts in subtypes of lymphoma and chronic lymphocytic leukemia. The speaker will update the M.D. Anderson Cancer Center outcome data of allografting after reduced intensity regimes in patients with follicular cell lymphoma and chronic lymphocytic leukemia. Results of allografting from other centers will be reviewed for the most common lymphoma subtypes, including mantle cell lymphoma.

Dr. Franco Locatelli will review the efficacy of reduced intensity regimes in securing engraftment in patients with nonmalignant disorders including hemoglobinopathies. These patients are most difficult to engraft, as they have been presensitized by blood transfusions. Therefore, results in this population offer a powerful benchmark to measure the potency of any regime for facilitating engraftment. Allografts from alternative donors are even more of a hurdle after reduced intensity regimes. Dr. Locatelli will review here the design of tolerable regimes that are effective in facilitating engraftment of unrelated donor grafts in patients with thalassemia.

Thrombophilia

Chair:

Andrew I. Schafer, MD, University of Pennsylvania School of Medicine, Philadelphia, PA

Speakers:

Agnes Y. Lee, MD, MSc, McMaster University and Hamilton Health Sciences, Henderson General Hospital, Hamilton, Ontario, Canada
Thrombosis and Cancer

Paula L. Bockenstedt, MD, University of Michigan, Ann Arbor, MI
Clinical Management of Hypercoagulable Disorders

Kenneth A. Bauer, MD, VA Boston Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
New Anticoagulants

Hematologists are increasingly engaged in the diagnosis and management of patients with thrombosis. There continues to be rapid progress in our understanding of acquired and inherited disorders of coagulation that lead to systemic hypercoagulable states. These advances are occurring in cancer with the development of novel antithrombotic strategies and clinical trials to provide clinicians with rational guidelines for therapy. This session will highlight some of the most important areas of progress in the field.

Dr. Agnes Lee will discuss the problem of thrombosis in cancer patients. Experimental studies have confirmed a strong biological link between activation of coagulation and tumor biology. Thrombosis is a common complication in patients with cancer and may be the first presentation of occult malignancy. Recent observational studies have shown that screening for underlying cancer in patients with unprovoked thrombosis does not improve clinical outcome. Management of thrombosis in oncology patients remains a challenge, but ongoing research is helping to identify prevention and treatment strategies that are safe and effective.

Dr. Paula Bockenstedt will discuss the initial and long-term management of hypercoagulable disorders. The presentation will highlight current concepts of anticoagulant bridging protocols, duration of anticoagulation for lower versus upper extremity venous thrombosis, treatment of less common sites of thrombosis, including retinal, cerebral sinus, visceral, portal vein, and organ graft thrombosis, and the management of prophylactic or therapeutic anticoagulation in the pregnant hypercoagulable patient.

Traditional anticoagulant drugs, such as unfractionated heparin and warfarin, have several limitations. Fondaparinux, a synthetic pentasaccharide that indirectly inhibits factor Xa, is a parenterally administered agent that is approved for the prevention and treatment of venous thromboembolism. Dr. Kenneth Bauer will review these anticoagulants as well as the current status and clinical development challenges faced by investigational oral direct factor Xa and thrombin inhibitors.

Pediatric Consultative Hematology

Chair:

Irene Roberts, MD, Hammersmith Hospital, Imperial College, London, United Kingdom

Speakers:

Reinhard Schneppenheim , MD, PhD, University Medical Center Hamburg - Eppendorf, Hamburg, Germany
Thrombosis in Infants and Children

Diane J. Nugent, MD, Children’s Hospital of Orange County, Orange, CA
Pediatric ITP and Neonatal Alloimmunization

Peter E. Newburger, MD, University of Massachusetts Medical School, Worcester, MA Neutrophil Disorders

Consultative pediatric hematology both provides a challenge to hematologists – that of making an accurate diagnosis with the minimum number of well-chosen investigations (since our patients are children rather than adults) – and also offers the exciting opportunity to unravel the mechanisms of complex, sometimes novel, inherited hematologic disorders.

Dr. Reinhard Schneppenheim will review the causes, clinical presentation, and management of thrombosis in newborns and older children. He will also discuss the indications for screening for inherited disorders in infants and children and interpretation of laboratory investigations in these age groups.

Dr. Diane Nugent will briefly outline the etiology and clinical presentation of acute and chronic immune thrombocytopenia purpura ( ITP) in children. She will focus on the ongoing controversies in management of childhood ITP, particularly when and how to treat and which treatment modalities to use. She will discuss the role of splenectomy and newer agents, including monoclonal antibodies. Management of neonatal alloimmune thrombocytopenia (NAIT) is also controversial. Dr. Nugent will summarise current views about the management of NAIT, as well as briefly outline the clinical presentation and diagnostic approach to neonates with severe thrombocytopenia.

Dr. Peter Newburger will provide a brief overview of normal neutrophil structure, function, and differentiation. He will then focus on inherited disorders of neutrophil production and neutrophil function. Several of these disorders, such as chronic granulomatous disease, have been investigated in great detail, not only providing fascinating insight into neutrophil function, but also leading to new developments in therapy. Elucidation of the molecular basis of other disorders, such as elastase mutations in severe chronic neutropenia (Kostmann disease), still leaves open many questions about their pathophysiologic basis. Advances in our understanding of the molecular and genetic basis of inherited neutrophil disorders will be discussed together with advice on management of affected children. As a balance to the rare disorders, Dr. Newburger will also discuss a pragmatic approach to the investigation of children with a suspected neutrophil disorder.

Hematology Grants Workshop

Saturday, December 9, 4:00 p.m. – 5:30 p.m.
This session will be offered only once.

Chair:

Bertram H. Lubin, MD, Children’s Hospital Oakland Research Institute, Oakland, CA

Speakers will include NIH Representatives from these Institutes:

National Cancer Institute
National Heart, Lung, and Blood Institute
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute on Aging

Securing funding from federal sources remains a challenge for many young researchers. The 2006 Hematology Grants Workshop explores a broad overview of funding mechanisms available and provides guidance on what federal agencies are looking for and what applicants need to do to be successful.

Representatives from NIH Institutes that support hematology and hematology-related research will highlight the specific funding requirements of their respective Institutes.

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