American Society of Hematology

2017 Education Spotlight Sessions

These sessions are intended to provide an in-depth review on specific scientific topics. This year, speakers will discuss current challenges and controversies in two exciting topics, addressing the current state of knowledge, translational and clinical applications, and future directions.

Each 90-minute session will be presented once in a small-venue format on either Sunday or Monday and will include ample time for audience questions and participation. These sessions are restricted to medical and research professionals only; no businesspersons or media will be admitted.

A Sticky Business: New Insights Into Neutrophil Extracellular Traps (NETs) in Physiology and Disease

Sunday, December 10, 2017, 4:30 p.m. - 6:00 p.m.
Georgia World Congress Center, Bldg B- Lvl 3- B302-B303

Neutrophils are the first leukocytes recruited to sites of infection or injury. A newly recognized component in their arsenal of responses is the release of nuclear DNA to generate neutrophil extracellular traps (NETs), which are web-like structures composed of decondensed chromatin coated with neutrophil nuclear, granule, and cytoplasmic proteins. Since first described in 2004 by investigators studying neutrophils activated in vitro, the regulation and clinical relevance of NETosis has attracted broad attention, yet many fundamental knowledge gaps remain. Mechanisms leading to NET formation are only partially understood, and include deimination of histones by peptidyl arginine deiminase 4 (PAD4). Released NETs can trap microbes and may contribute to host defense, but the importance of this function is controversial. NETs can also cause proinflammatory damage to host tissues, and the NETs themselves are highly proinflammatory and prothrombotic. 

Dr. Christian Yost will provide an overview of NETosis and its proposed beneficial effects and adverse consequences. He will present recent studies of human neonates leading to discovery of a family of peptide inhibitors of NETosis. Investigation of the activities of these inhibitors is relevant to the inflammatory biology of neonates and adults, and may lead to new therapeutic strategies to harness NET formation.

Dr. Denisa Wagner will discuss the evidence supporting an important role of NETs in thrombosis and inflammation. Mice lacking PAD4 or mice treated with deoxyribonuclease (DNase) I are protected from venous thrombosis and aging-associated fibrosis, and develop smaller post-ischemic cardiac infarcts. Dr. Wagner will propose why PAD4 and NETs will be an interesting drug target in thrombotic and cardiovascular disease.

Speakers:

Christian Yost, MD
University of Utah
Salt Lake City, UT
NETs as Friends or Foes: Lessons From Human Neonates and Translational Models

Denisa D. Wagner, PhD
Boston Children's Hospital/Harvard Medical School
Boston, MA
NETs: "Nuclear" Weapons of Inflammation

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Getting Patients to Transplant: Myths and Reality

Sunday, December 10, 2017, 4:30 p.m. - 6:00 p.m.
Georgia World Congress Center, Bldg B- Lvl 3- B304-B305

Allogeneic hematopoietic stem cell transplantation (alloHCT) remains the best treatment for a broad range of hematologic diseases. The field has seen remarkable advances in the past two decades, with improved outcomes and access to transplantation, especially for patients who are older or from minority communities historically underrepresented in transplant registries.

For the first time in history, nearly all patients who require alloHCT have one or more potential donors available, including matched related and unrelated donors, umbilical cord grafts, and haploidentical family members. Unfortunately, many primary hematologists and transplant specialists find this multiplicity of options confusing or intimidating, and they are finding it more difficult than ever to counsel patients about which transplant path is best.

The development of reduced-intensity and nonmyeloablative conditioning has also made it increasingly possible to perform alloHCT in older patients, with overall survival rates steadily improving. Most centers are now comfortable transplanting selected septuagenarians following comorbidity screening. Despite these advances, population studies demonstrate that even for widely supported indications (e.g., autologous HCT for myeloma and alloHCT for high-risk acute myeloid leukemia) only a minority of suitable patients ever reach a transplant. Thus, the issue of barriers to transplant remains a critical problem. This spotlight session will highlight these critical issues of donor graft selection and the barriers that limit transplant access and utilization.

Dr. Daniel Weisdorf will discuss the array of donor and graft choices available for alloHCT recipients and discuss principles that should govern clinical decision making.

Dr. Navneet Majhail will place recent advances in the context of remaining barriers to HCT that can be improved by coordinated efforts of referring hematologists and HCT clinicians.

Speakers:

Daniel J. Weisdorf, MD
University of Minnesota
Minneapolis, MN
Too Many Donors to Choose From: Which Way Do We Turn?

Navneet S. Majhail, MD, MS
Cleveland Clinic
Cleveland, OH
Getting Patients to Transplant: Barriers and Bridges

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Emerging Pathogens from A to Zika and Their Impact on Transfusion Safety

Monday, December 11, 2017, 10:30 a.m. - 12:00 p.m.
Georgia World Congress Center, Bldg B- Lvl 2- B211-B212

Serological assays, which have been implemented over the past five decades, have proven to be effective for screening out donors who are chronically infected with the classic transfusion-transmitted infectious diseases (TTIDs), such as syphilis, hepatitis B virus, human immunodeficiency virus, hepatitis C virus, and human T-cell leukemia-lymphoma virus types I and II. However, over the past 15 years nucleic acid amplification technology (NAT) screening has proven to be the preferred option for detection of many emerging infectious diseases (EIDs) that generally cause acute infections. These EIDs include parvovirus B19, hepatitis E virus, babesia, and multiple transfusion-transmitted arboviruses, such as West Nile, dengue, chikungunya, and Zika. Such infections are effectively interdicted by NAT, whereas serological testing is ineffective and would detect high rates of donors with resolved infections. This session will review the evolution of responses to TTIDs, with a focus on the global Zika virus epidemic, and will highlight why ongoing surveillance for and rapid response to EIDs, optimally with sensitive multiplexed NAT assays, is critical to maintaining global blood safety.

Speakers:

Lyle R. Petersen, MD, MPH
National Center For Emerging and Zoonotic Infectious Diseases
Fort Collins, CO
Emerging Infectious Diseases: Clinical Significance and Implications for Transfusion

Susan L. Stramer, PhD
American Red Cross
Washington, DC
Prevention of Pathogen Transmission via Blood Transfusion

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Debate: Patients With Acquired TTP in Remission Should Be Treated to Prevent Relapse

Monday, December 11, 2017, 10:30 a.m. - 12:00 p.m.
Georgia World Congress Center, Bldg B- Lvl 2- B206

Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13 that result in severe ADAMTS13 deficiency. TTP usually remits when treated with plasma exchange, however, patients tend to relapse if the autoantibodies persist. Immunosuppression with rituximab can prevent most of these relapses, whether given to all patients at the time of presentation or reserved for disease that is refractory to plasma exchange. The efficacy of rituximab in these settings raises the question of whether patients with asymptomatic severe ADAMTS13 deficiency should be treated preemptively to prevent future relapses. Answering this question depends on understanding both the risk of relapse associated with persistent severe ADAMTS13 deficiency and the risk of adverse events associated with rituximab or other immunosuppressive regimens. Most patients with severe ADAMTS13 deficiency relapse fairly quickly, but some remain asymptomatic for years. Most patients tolerate rituximab well, but rare patients experience serious adverse events that can be fatal, such as progressive multifocal leukoencephalopathy. Some hematologists believe that the data available already justify preemptive treatment to restore ADAMTS13 activity, but others believe that more clinical research is needed before a well-informed decision can be made. Speakers in this session will review the evidence on both sides of the question and consider how to reach a definitive answer.

Speakers:

Paul Coppo, MD, PhD
Saint-Antoine Hospital
Paris, France
The Case For

James N. George, MD
University of Oklahoma
Oklahoma City, OK
The Case Against

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Identification and Management of Toxicities Induced by Immunotherapies

Monday, December 11, 2017, 2:45 p.m. - 4:15 p.m.
Georgia World Congress Center, Bldg B- Lvl 2- B206

Over the past few years, immune checkpoint inhibitors that can reverse tumor-induced T-cell suppression mediated by inhibitory ligands have produced impressive clinical responses in a broad spectrum of cancers, including several hematologic malignancies. Similarly, T cells genetically modified with chimeric antigen receptors (CARs) to confer specificity for surface antigens such as CD19 have produced extremely high response rates in acute lymphocytic leukemia and have also shown promising activity in B-cell lymphomas and chronic lymphocytic leukemia. However, both of these promising immunomodulatory strategies have toxicities. Checkpoint inhibition may cause autoimmune toxicities such as pneumonitis, pancreatitis, and colitis, while cytokine release syndrome (CRS), neurologic toxicities, and hypersensitivity reactions to CAR constructs have all been observed after CAR T-cell infusions.

Dr. Daniel Lee will discuss identification grading and management of toxicities occurring in patients receiving T cells genetically modified to express CARs.

Dr. Suzanne Topalian will discuss immune-related side effects of checkpoint inhibitors and outline how management can be guided by an understanding of the mechanisms.

Speakers:

Daniel W. Lee III, MD
University of Virginia
Charlottesville, VA
Toxicities of Chimeric Antigen Receptor T Cells

Suzanne L. Topalian, MD
The Johns Hopkins University
Baltimore, MD
Toxicities of Checkpoint Inhibitors

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