Programs

Scientific Spotlight Sessions

Cellular Breakups: Transfusion and Hyperhemolysis in Sickle Cell Disease

Sunday, December 6, 2020, 12:00 p.m. - 12:45 p.m. Pacific time

Please view the pre-recorded presentations prior to attending the corresponding Live Q&A session. Access to the on-demand content will be available starting on December 2 and will continue through the duration of your meeting subscription. CME is available for participation in the corresponding Live Q&A.

Transfusions remain a cornerstone treatment for patients with sickle cell disease. However, patients can develop potentially fatal hyperhemolytic transfusion complications, estimated to account for 4% of all sickle cell patient deaths, but since the clinical symptoms mimic those of in sickle cell pain crisis, it is likely that this rate underestimates the true incidence. In addition, the occurrence and progression of such hemolytic reactions from mild to severe is unpredictable. Mechanistic insight into how this complication develops and its pathologic consequences can lead to better prevention and treatment options for this life-threatening condition which is mostly encountered in sickle cell disease. This session will present recent developments in our understanding of potential mechanisms that may account for increased red cell destruction, including heme-driven alternative complement activation pathways, autoantibody-mediated destruction of patient's own red cells, and altered innate immune activation including those of phagocytes, and describe promising therapeutic strategies to control the associated inflammatory response for this complication in sickle cell disease.

Dr. Lubka Roumenina will focus on mechanisms of overactivation of the innate immune inflammatory complement system in circulation and tissues innate in sickle cell disease. She will discuss recent work showing that dense erythrocytes as well as intravascular hemolysis-derived products, heme and erythrocyte microvesicles, are key activators of the complement cascade. In addition, she will describe how heme can render the vascular endothelium susceptible to complement attack in a TLR4/P-selectin-dependent manner. This work has implications for understanding the role of heme and complement in heme-driven pathology in sickle cell disease and also underscores the use of complement inhibition and heme scavenging as potential promising therapeutic strategies to control inflammation in hyperhemolytic conditions in sickle cell disease patients.
Dr. Karina Yazdanbakhsh will focus on the mechanisms of hemolytic transfusion reactions in sickle cell disease. Development of alloantibodies against transfused red cells account for hyperhemolytic reactions. Nevertheless, in about one third of cases, no antibodies can be detected, but the mechanisms for increased red cell destruction remain largely unexplained. Dr. Yazdanbakhsh will discuss the role of hemolysis and systemic inflammatory response in the activation of monocyte, macrophage and dendritic cells that drive extravascular red cell destruction in sickle cell disease. In addition, she will describe how in some patients, dysregulation in cell intrinsic heme response pathways may initiate the hyperhemolytic reaction due to the cell’s inability to tolerate any degree of excess heme and hemolytic insult. She will also discuss the potential for therapeutic manipulations of these pathways to reverse and dampen the associated inflammation in patients who suffer from these life-threatening transfusion complications.

Chair:

Karina Yazdanbakhsh , PhD
New York Blood Center
New York,  NY

Speakers:

Lubka T. Roumenina
Centre De Recherche Des Cordeliers
Paris,  France
Pathophysiology of Sickle Cell Disease: Complement in Bystander Hemolysis

Karina Yazdanbakhsh , PhD
New York Blood Center
New York,  NY
Immune Effector Responses to Hemolysis in Sickle Cell Disease

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Checkpoint Blockade: Defining A New Treatment Paradigm in Hodgkin Lymphoma and Allogeneic Transplantation

Sunday, December 6, 2020, 12:00 p.m. - 12:45 p.m. Pacific time

Please view the pre-recorded presentations prior to attending the corresponding Live Q&A session. Access to the on-demand content will be available starting on December 2 and will continue through the duration of your meeting subscription. CME is available for participation in the corresponding Live Q&A.

Discussed will be the current role of allogeneic hematopoietic cell transplantation in Hodgkin Lymphoma.  With the advent of novel therapies including the antibody drug conjugate brentuximab vedotin and the checkpoint inhibitors nivolumab and pembrolizumab, outcomes in patients with Hodgkin Lymphoma have continued to improve, even in patients with more high risk disease.  Concomitant with this progress, the number of patients referred for allogeneic HCT has decreased.  Nevertheless, recent data suggest that patients with Hodgkin Lymphoma who undergo allogeneic HCT after exposure to checkpoint inhibitors have remarkable overall survival.  The discussion will review recent data for allogeneic HCT in the era of checkpoint inhibitors including sequencing of therapies, and the impact of checkpoint inhibitors on GVHD, GVL and immune-related adverse events.

Chair:

Leslie Kean , MD, PhD
Boston Children's Hospital
Boston,  MA

Speakers:

Margaret A. Shipp , MD
Dana Farber Cancer Institute
Boston,  MA
It's All In The Genes: What Hodgkin Lymphoma Teaches Us About Checkpoint Blockade

Miguel-Angel Perales , MD
Memorial Sloan Kettering Cancer Center
New York,  NY
Why Allo-Transplant Still Matters For Hodgkin Lymphoma In The Era Of Checkpoint Blockade

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