Special Scientific Symposia
View the final 2020 program below. Please check back in July 2021 to view the preliminary schedule and program for the 63rd ASH Annual Meeting and Exposition.
|Sunday, December 6, 2020, 9:30 a.m. - 10:15 a.m. Pacific time|
The importance of the intestinal microbiome for graft-versus-host disease (GvHD) after allogeneic hematopoietic cell transplantation (allo-HCT) was initially demonstrated both in preclinical and clinical studies several decades ago. Since then major advances in microbiome research have resulted in a better understanding of the interplay between microbiome and host in health and disease. This session will address various aspects of the role of the intestinal microbiome in patients with hematological malignancies (especially allo-HCT recipients), including novel methodologies to study interactions between microbiome and host, preclinical and clinical studies regarding the intestinal microbiome and GvHD and the clinical potential of fecal microbiota transplant in allo-HCT patients.
Dr. Ami Bhatt will discuss how alterations in the human gut microbiome are correlated with disease prognosis, treatment response, and complications of therapy in patients with hematologic disorders. Recently developed technologies and bioinformatic approaches have enabled us to understand the mechanisms that might underlie these interactions. By understanding microbes at the strain level and defining the macromolecules that microbes use to communicate with one another and the host, her lab hopes to characterize the rich signaling interface between microbes in humans. In so doing, it is anticipated that modifying and eventually controlling this type of signaling could help improve patient outcomes.
Dr. Marcel van den Brink will discuss preclinical and clinical studies demonstrating the role of changes in the intestinal microbiota of recipients of allo-HCT and its effects on GvHD, as well as infections, relapse and engraftment.
Dr. Mette Hazenburg will discuss how disruption of the intestinal microbiome is a key element of GvHD pathophysiology. This has led to the hypothesis that with fecal microbiota transplantation (FMT) the damaged microbiome can be repaired by FMT, and that reparation of the microbiome may cure GvHD. By inference, it can be hypothesized that reconstitution of a healthy microbiome before or shortly after allogeneic HCT by FMT could prevent severe GvHD. In this presentation, both hypotheses will be addressed, based on the literature available and also including Dr. Hazenburg’s own data on FMT in steroid-refractory patients.
Marcel van den Brink
Memorial Sloan- Kettering Cancer Center
New York, NY
Ami S. Bhatt
Basic Biology of the Microbiome Universe
Marcel van den Brink
Memorial Sloan- Kettering Cancer Center
New York, NY
The Microbiome and Graft Versus Host Disease
M.D. D. Hazenberg
Fecal Microbiota Transplants
|Sunday, December 6, 2020, 2:00 p.m. - 2:45 p.m. Pacific time|
Hematologists are often asked to weigh-in on the risks and benefits of exogenous hormone administration for non-hematologic indications. Meanwhile, aberrant hormone signaling pathways contribute to common and unusual hematologic conditions. This unique session explores the hematologic significances of exogenous hormone administration to transgender individuals, how estrogen-platelet signaling pathways contribute to sex-differences in platelet function and thrombotic risks, and the role of steroids in erythropoiesis.
Dr. Jean Connors will discuss the impact of exogenous hormones on the individual patient, reviewing both physiologic changes and effects on risk profiles for adverse events important for hematologists to understand. Unique risks and benefits of the use of specific hormones in cisgender and transgender patients will be explored using a case-based presentation format.
Dr. Dale Abel will present on data that demonstrates how OPA1 expression in platelets is increased in females and correlates with increased risk of thrombosis. Platelet OPA1 levels are regulated by estrogen. In female mice, genetic deletion of OPA1 in platelets reduces platelet function and in vivo thrombosis. In contrast, in male mice, genetic deletion of OPA1 in males leads to increased thrombosis and is reversed by increasing circulating levels of estrogen. The mechanism and potential impact of this novel estrogen regulated pathway will be explored in various thrombosis models and clinical contexts.
Dr. Robert Richard will address the role of steroids in erythropoiesis. The important role of steroids in red blood cell development was described over 50 years ago. Recent studies remind us that steroids have a central role in erythropoiesis as well as continuing therapeutic potential. Androgens have been the most studied steroid, but other steroid dependent pathways play an equally important role. Studies using corticosteroids in Diamond-Blackfan Anemia (DBA) point to signaling pathways that synergize with the glucocorticoid receptor. Identification of erythroid progenitors with increased sensitivity to glucocorticoids could lead to improvements in steroid based therapies for DBA and perhaps other underproduction anemias.
Lydia H. Pecker
Johns Hopkins University
Jean M. Connors
Brigham & Women's Hospital
Coagulation Issues in Transgender Individuals
E. Dale Abel
, MD, PhD
University of Iowa
Iowa City, IA
OPA1 A Novel Regulator of Sex-Dependent Differences in Thrombosis
, MD, PhD
Veterans Affairs Puget Sound Health Care System
Steroids and Erythropoeisis: We're Going to Pump You Up
|Monday, December 7, 2020, 1:30 p.m. - 2:15 p.m. Pacific time|
It has become increasingly evident that inflammatory processes are intimately linked with the hemostatic system. In this joint session, these interactions are highlighted in three talks focusing on recent progress in the field of coagulation, vascular biology and platelet research. Coagulation activation is a driving force for vascular dysfunction in sickle cell disease. Conversely, genetic predisposition leading to vascular dysfunction in cerebral cavernous malformations promotes hemorrhage by overactivation of the anticoagulant pathway. The autoimmune pathology of heparin-induced thrombocytopenia is moreover critically dependent on the activation of the humoral complement defense pathway. The session will discuss implications of these links for therapies of thrombotic and vascular disorders.
Dr. Rafal Pawlinski will discuss the interplay between coagulation and inflammation in sickle cell disease (SCD). Contribution of vascular inflammation and hypercoagulable state to the pathology of SCD has been recently recognized. Chronic activation of coagulation not only leads to the increased incidence of pro-thrombotic complications, but it is also an important mediator of vascular inflammation and end-organ damage observed in SCD. Preliminary data from Dr. Pawlinski’s lab indicates that inhibiting the activation of the intrinsic coagulation and/or contact pathways by targeting factor XIIa could provide benefits associated with reduced thrombosis, vascular inflammation and end-organ damage in SCD without increasing risk of bleeding complications.
Dr. Mark Ginsberg will discuss vascular signaling in the pathology of cerebral cavernous malformations (CCM). CCM are common brain vascular malformations prone to acute and chronic hemorrhage with significant clinical sequelae. Endothelial cell specific deletion of CCM susceptibility genes (Krit1, Pdcd10) in mice identified upregulation of transcription factors KLF2 and KLF4 as the cause for elevated expression of anticoagulant endothelial receptors. The resulting excessive generation of activated protein C(APC) contributes to CCM hemorrhage and blocking antibodies to anticoagulant endothelial receptors reduce CCM hemorrhage. Plasma levels of soluble thrombomodulin may represent a biomarker for hemorrhagic risk in CCMs and regulators of the Protein C pathway are potential targets for reducing hemorrhage in CCM.
Dr. Gowthami Arepally will discuss the role of complement activation in the pathogenesis of heparin induced thrombocytopenia (HIT). HIT is an aggressive thrombotic disorder initiated by ultra-large immune complexes (ULICs) containing IgG antibodies to a multivalent antigen composed of platelet factor 4 (PF4) and heparin (H). Patients with HIT remain at risk of death and major morbidity despite optimum anticoagulation. The mechanisms underlying thrombosis in HIT are only partially understood. HIT ULICs activate cellular FcgRIIA to initiate diverse cellular effector functions that engender a prothrombotic environment. However, ULICs also exert other biologic effects. HIT serum and IgG robustly activate complement leading to its deposition on endothelial cells and circulating platelets. To what extent these disparate activities of HIT ULICs contribute to the hypercoagulable state in HIT is not known. In this session, Dr. Arepally will review recent data showing that the complement activating effects of HIT antibodies essentially mediate FcgR-dependent cellular activation. Using in vitro and in vivo models, they demonstrate that HIT ULICs activate complement via the classical pathway, mediate cellular activation via FcgRIIA and support the procoagulant effects of HIT antibodies. These studies provide a rationale for developing non-anticoagulant interventions in HIT and insights into the contribution of complement to other immune-complex mediated thrombotic disorders.
Johannes Gutenberg University Medical Center
Mainz, CA, Germany
Angara Koneti Rao
University of North Carolina
Chapel Hill, NC
Hemostasis: Coagulation and Inflammation
Mark H Ginsberg
University of California - San Diego
La Jolla, CA
Thrombosis/Vascular Biology: Cavernous Malformations and Thrombosis
Gowthami M. Arepally
Duke University Medical Center
Complement Activation in Heparin Induced Thrombocytopenia
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna
Association of ABO Blood Group with Bleeding Severity in Patients with Bleeding of Unknown Cause