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2024 Ham-Wasserman Lecture

Sickle cell disease (SCD) is an inherited red blood cell (RBC) disorder caused by either homozygous inheritance of the hemoglobin S mutation (HbSS), or compound heterozygous inheritance of the hemoglobin S mutation with another ß-globin chain abnormality. India has among the highest hemoglobin S allele frequencies in the world and the third-highest birth rate for babies born with HbSS.��

The Indian sickle cell haplotype is associated with the Arab-Indian or Asian haplotype and is associated with high fetal hemoglobin (HbF) levels and hence, is believed to have mild clinical presentation as compared to other populations. ��

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In this lecture Dr. Dipty Jain will discuss the status of frequency, comorbidities, and management of sickle cell disease (SCD) in India, which is characterized by relatively high percentages of fetal hemoglobin, accompanied by mild to severe complications observed globally. Additionally she will talk about targeted newborn screening and fixed low dose of hydroxyurea in managing children with sickle cell disease in India.��

Dr. Jain will discuss the milestones and progress in understanding sickle cell disease (SCD) phenotype accelerated by the Government of India’s ambitious ‘’National Sickle Cell Anemia Elimination Mission 2023’’ with comprehensive guidelines and implementation of screening, treat, counsel, educate, development of technology and novel therapies including gene therapy specific to the requirement of India’s population with sickle cell disease (SCD).��

Chair:

Mohandas��Narla,��DSc
New York Blood Center
New York,��NY

Speaker:

Dipty Lalit��Jain
Indira Gandhi Government Medical College and Hospital
NAGPUR,��India
Sickle Cell Disease in Developing Countries

2024 Presidential Symposium

Red cells constitute ~70% of all cells in the human body and in healthy individuals their circulatory life span is ~ 120 days. At steady state the bone marrow produces 2.5 million red cells per second to maintain normal hemoglobin levels. Anemia characterized by decreased hemoglobin levels is a major global health problem affecting nearly 2 billion individuals. Decreased red cell life span and/or decreased red cell production in the bone marrow account for anemia in various inherited and acquired hemolytic anemias. Significant progress has been and is continuing to be made in our understanding of the mechanistic basis for anemia. The three presentations in the symposium will highlight recent advances in our understanding of red cell biology and of anemia.

Dr. Patrick Gallagher will discuss recent advances which have expanded understanding of the many roles of the erythrocyte membrane. An update on the diagnosis and treatment of membrane disorders and potential emerging therapies will be discussed.

Dr. Naomi Taylor will highlight the pivotal role of metabolite transporters and fuel choice in erythroid lineage commitment and terminal erythroid differentiation. The importance of metabolic reprogramming in diseases of disordered and ineffective erythropoiesis will be discussed.

Dr. Olivier Hermine will explain the mechanisms that control red cell production during terminal erythroid differentiation, focusing on the processes that determine the fate of erythroid precursors between differentiation or cell death. The discussion will also touch upon how these mechanisms are impacted in hemoglobinopathies and myelodysplastic disorders, which can result in ineffective erythropoiesis and anemia. Additionally, therapeutic implications arising from these insights will be emphasized.

Chair:

Mohandas��Narla,��DSc
New York Blood Center
New York,��NY

Speakers:

Patrick G��Gallagher,��MD
Abigail Wexner Research Institute at Nationwide Children's Hospital
Columbus,��OH
Mature Red Cell Membrane Disorders (including genome-wide screening and PK activators)

Naomi��Taylor,��MD
National Institutes of Health
Bethesda,��MD
Metabolism and Erythropoiesis (including metabolism, IDH mutations and relevance to MDS, sideroblastic anemia)

Olivier��Hermine,��MD,PhD
IMAGINE institute Paris France
Paris,��France
Ineffective Erythropoiesis in Thalassemia and Sickle Cell Disease

Announcement of Awards: Wallace H. Coulter Award for Lifetime Achievement in Hematology, ASH Mentor Awards, and the ASH Award for Leadership in Promoting Diversity

WALLACE H. COULTER AWARD FOR LIFETIME ACHIEVEMENT IN HEMATOLOGY

Wallace H. Coulter was a prolific inventor, innovator, and entrepreneur. His Coulter Principle pioneered the development of flow cytometry, defined particle characterization, and made possible automated hematology, thus revolutionizing laboratory medicine. The Coulter Counter led to major breakthroughs in science, medicine, and industry. This award, in his name, recognizes an individual who has demonstrated a lasting commitment to the field of hematology through outstanding contributions to education, research, and practice.

ASH will recognize Éliane Gluckman, MD, PhD, of the University of Paris, with the 2024 Wallace H. Coulter Award for Lifetime Achievement in Hematology. Dr. Gluckman, a renowned physician-scientist and thought leader, is being honored for a lifetime of achievement in cord blood transplantation. She performed the world’s first human cord blood transplant, which established cord blood as an alternative stem cell source for patients in need of hematopoietic cell transplantation and shortened the delay between donor identification and actual transplant. Since that revolutionary procedure in 1988, there have been more than 40,000 transplants, with cord blood registries established worldwide. ��

As a young medical student, Dr. Gluckman was drawn to hematology, a relatively new discipline at the time, because of its potential for growth and innovation. Her first residency position was in the hematology ward at the Hôtel-Dieu Hospital in Paris, where she affirmed her passion and interest in Fanconi anemia and sickle cell disease (SCD). From 1988, she led cord blood research as medical director of the bone marrow transplant service and head of the department of hematology at the Saint-Louis Hospital in Paris. Currently, she is head of the EuroCord research group on cell therapy for malignant and non-malignant diseases in children.��

Dr. Gluckman has continued to shape hematology. Her impact includes significant contributions to the understanding of hematologic disorders such as aplastic anemia, Fanconi anemia, and sickle cell disease through the design of new conditioning protocols that?are used to prepare patients for stem cell transplantation.��

Dr. Gluckman is currently leading a project that examines immunogenetic factors that could predict the outcomes and probability of finding a donor for stem cell transplants in people living with sickle cell disease and other hereditary disorders. She has trained many investigators in the field and helped establish bone marrow transplant units in their respective countries.��

ASH MENTOR AWARDS

The ASH Mentor Award was established to recognize hematologists who have excelled in mentoring trainees and colleagues. Each year the Society recognizes two outstanding mentors�� who have had a significant, positive impact on their mentees' careers and, through their mentees, have advanced research and patient care in the field of hematology.

ASH will recognize Stephen D. Nimer, MD, of the Sylvester Comprehensive Cancer Center, with the 2024 ASH Mentor Award. Dr. Nimer, a physician-scientist specializing in myeloid leukemia and myelodysplastic syndromes, is being honored for his impact on more than 100 hematology trainees with his tailored, encouraging, and community-focused mentorship. Dr. Nimer serves as a role model for trainees and instills in them the importance of thinking critically and embracing challenges. His willingness to provide feedback, dedication to seizing growth opportunities, and catchy “Nimer-isms” have all helped propel mentees into thriving careers, with many receiving career development awards from foundations and federal agencies. A hallmark of his mentorship is the sense of community he creates, demonstrated by more than 20 years of annual Nimer lab breakfasts at the ASH annual meeting, during which, even long after leaving his lab, mentees share their progress and seek Dr. Nimer’s advice.��

ASH will recognize Charles A. Schiffer, MD, of the Karmanos Cancer Institute and Wayne State University School of Medicine, with the 2024 ASH Mentor Award. For Dr. Schiffer, an expert in platelet transfusion therapy and the treatment of adult leukemias, mentoring the next generation of hematologists comes naturally. Dr. Schiffer leads by example and challenges trainees to remain curious, seize opportunities, and think creatively. His mentees have described him as a one-of-a-kind generational teacher and characterize him as a “mentor of mentors.” Dr. Schiffer is widely known for his open-door approach and fine-tuned ability to provide clinical care with rigor, bright humor, and compassion. He has trained large numbers of successful clinical investigators whose contributions have substantially influenced leukemia and cancer research and improved patient outcomes.��

ASH AWARD FOR LEADERSHIP IN PROMOTING DIVERSITY

The ASH Award for Leadership in Promoting Diversity honors hematologists who have supported the development of an inclusive hematology workforce, who have encouraged the career development of underrepresented minority trainees, who have made the commitment to inclusiveness in contributions to the mission of ASH, or who have made accomplishments that aim to eliminate health disparities in the care of hematology patients.

ASH will recognize James George, MD, of the University of Oklahoma, with the 2024 ASH Award for Leadership in Promoting Diversity. Dr. George is being honored for his exemplary leadership in building a stronger, more diverse hematology workforce. Under his leadership as ASH President in 2005, the Society collaborated with the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Program (AMFDP) to create ASH-funded AMFDP positions in hematology. Since the pr�Dz�������’s inception, ASH has supported nearly 30 recipients, many of whom have risen to the ranks of senior faculty in their institutions.����

Dr. George was also a strong supporter of the ASH Minority Medical Student Award Program (MMSAP), which provides research support for medical students underrepresented in medicine to encourage them to pursue hematology. To date, the MMSAP has supported more than 300 research opportunities for medical students. Additionally, Dr. George codeveloped and directed the ASH Clinical Research Training Institute (CRTI), an inclusive yearlong program that offers broad education for clinicians on clinical research methods. Dr. George has continued to mentor the next generation of hematologists, including mentees from backgrounds underrepresented in medicine, international students, women, and individuals of lower socioeconomic status.

Chair:

Mohandas��Narla,��DSc
New York Blood Center
New York,��NY

Announcement of Awards: William Dameshek Prize and Henry M. Stratton Medals

WILLIAM DAMESHEK PRIZE

The William Dameshek Prize, named for the late William Dameshek, MD, a past president of ASH and the original editor of Blood, recognizes an early- or mid-career individual who has made a recent outstanding contribution to the field of hematology.

ASH will recognize Ami Bhatt, MD, PhD, of Stanford Medicine, with the 2024 William Dameshek Prize. Dr. Bhatt is being honored for pioneering the development and application of genomic approaches to studying the microbiome — work that has improved outcomes for many human diseases. She has applied microbiomics in the clinical setting to study the impact of gut decontamination on transplant outcomes and has co-led efforts to study the microbiome in the context of evolving graft-versus-host disease prophylaxis strategies. Dr. Bhatt successfully linked bloodstream infections and outcomes in transplant patients to characteristics within the gut microbiome and uncovered a link between prolonged gastrointestinal SARS-CoV-2 viral shedding and gastrointestinal symptoms, among other major findings. Her unique and highly collaborative work has broad implications across biomedicine, with her landmark research resulting in a broad expansion of knowledge on microbial enzymes that can be developed for gene therapy.��

HENRY M. STRATTON MEDAL

The Henry M. Stratton Medal is named after the late Henry Maurice Stratton, co-founder of Grune and Stratton, the medical publishing house that first published ASH’s journal Blood. The prize honors two senior investigators whose contributions to both basic and clinical/ translational hematology research are well recognized and have taken place over a period of several years.

ASH will recognize Douglas Cines, MD, of the Perelman School of Medicine at the University of Pennsylvania, with the 2024 Henry M. Stratton Medal for basic science. Dr. Cines is being honored for more than 40 years of research discoveries that have led to significant increases in the understanding and treatment of thrombocytopenic disorders, including immune thrombocytopenia, heparin-induced thrombocytopenia (HIT), and thrombocytopenia in pregnancy. Dr. Cines’ main research interest is immunothrombosis, or how the immune system and coagulation interact. He was instrumental in identifying the role of endothelial cells — which help regulate clotting and breakdown of blood clots — as targets of immune injury in lupus, HIT, and antiphospholipid syndrome, thereby providing a rationale for the connection of these disorders to thrombosis.��

ASH will recognize Katherine High, MD, of The Rockefeller University, with the 2024 Henry M. Stratton Medal for translational/clinical science. Dr. High is being honored for spearheading the development of a gene therapy for hemophilia B, approved earlier this year by the U.S. Food and Drug Administration (FDA) and Health Canada. This success comes after more than two decades of challenging research during which she directly contributed to the understanding of DNA defects in hemophilia B, factor VII, and factor X, as well as performed several first-of-their-kind clinical trials in gene therapy, including the first intramuscular and intravascular administrations of an adeno-associated viral vector. These studies resulted in adverse events that were not predicted by animal studies, the basis for which she unraveled in bedside-to-bench laboratory investigations. Dr. High’s research interests, sparked by a chemistry set she was gifted at age 10, also extend to inherited blindness. She was instrumental in developing a gene therapy to restore vision loss in patients with this condition, the first-ever gene therapy for genetic disease to be approved by the FDA in 2017.��

Chair:

Mohandas��Narla,��DSc
New York Blood Center
New York,��NY

ASH-EHA Joint Symposium

Session Overview

The ASH-EHA Joint Symposium is intended to address global issues in hematology from both the North American and European perspectives and provide insight on how international collaboration can help confront these issues. The first of these sessions was held at the ASH Annual Meeting in December 2005, and has taken place twice each year since at the European Hematology Association’s (EHA) Annual Congress in June and the ASH Annual Meeting in December. The leadership of both societies determine the recommended topics and speakers for these events each year, with the society presidents co-chairing the event. This year's topic is Myelodysplasia. ��

Myelodysplasia

Myelodysplasia and Myeloproliferative syndromes are complex and heterogeneous clinical entities with varying progression rates. Significant progress is being made in our understanding of the molecular and genetic basis for these disorders. These insights are being used to develop new strategies for optimal patient-specific treatment modalities for effective and optimal clinical management of these disorders.�� Dr. Amy DeZern will discuss prognostication and risk stratification strategies for patients with myelodysplastic syndromes. Dr. Matteo Della Porta will discuss the targeting of cytopenias in low-risk MDS.

Co-Chairs:

Mohandas��Narla,��DSc
New York Blood Center
New York,��NY

Antonio Medina��Almeida,��MD,PhD
Hospital da Luz Lisboa
Lisbon,��Portugal

Speakers:

Amy E.��DeZern,��MD
Johns Hopkins University
Baltimore,��MD
Prognostication and risk stratification strategies for patients with myelodysplastic syndromes

Matteo Giovanni��Della Porta,��MD
IRCCS Humanitas Research Hospital
Rozzano,��Milan,��Italy
Targeting of Cytopenias in Low-Risk MDS

Best of ASH

Best of ASH (BOA) highlights the most cutting-edge science presented in the oral abstract sessions during the Annual Meeting. This year’s session will consist of talks arranged in arranged in 3-4 overarching themes and will be presented by the 2024 Scientific Program Co-Chairs: Drs. Jennifer Trowbridge (The Jackson Laboratory) and Sant-Rayn Pasricha (Walter and Eliza Hall Institute of Medical Research).

Since BOA highlights the research of other investigators, there will be no question and answer following the speakers’ presentations.

Co-Chairs:

Jennifer J.��Trowbridge,��PhD
The Jackson Laboratory
Bar Harbor,��ME

Sant-Rayn��Pasricha,��MD,PhD
Walter and Eliza Hall Institute of Medical Research
Fitzroy North,��VIC,��Australia

E. Donnall Thomas Lecture and Prize

Hematopoietic Stem Cell Maintenance

In studying the intrinsic and extrinsic mechanisms that regulate hematopoietic stem cell (HSC) maintenance and the roles these mechanisms play in cancer, Dr. Morrison and others identified a series of self-renewal regulators, revealing important principles. First, stem cell self-renewal is mechanistically distinct from restricted progenitor proliferation. Second, self-renewal mechanisms are conserved among stem cells in different tissues. Third, these mechanisms comprise networks of proto-oncogenes and tumor suppressors that are dysregulated in cancer. These networks change over time, conferring temporal changes in stem cell properties that match the changing growth and regeneration demands of tissues. Tumor suppressor expression increases with age in stem cells, suppressing cancer development but also reducing tissue regenerative capacity during aging.

In terms of cell-extrinsic mechanisms, HSC niches in adult bone marrow and spleen have been identified. They are closely associated with sinusoidal blood vessels in both tissues. Leptin Receptor-expressing (LepR⁺) perivascular stromal cells and endothelial cells are the sources of factors required for HSC maintenance in the bone marrow. The identification of these cells has revealed new mechanisms that regulate hematopoiesis in the bone marrow. There are distinct subsets of LepR⁺ cells that create perivascular niches for HSCs and restricted hematopoietic progenitors throughout the bone marrow. LepR⁺ cells also synthesize growth factors that regulate osteogenesis, vascular regeneration, and peripheral nerve maintenance in the bone marrow. A subset of LepR⁺ cells are the skeletal (mesenchymal) stem cells that give rise to the osteoblasts and adipocytes that are produced in adult bone marrow.

This lecture will focus on new insights that have been gained into the mechanisms that regulate HSC maintenance, hematopoiesis, and osteogenesis in the bone marrow as a result of identifying LepR⁺ stromal cells, as well as the implications of these findings for clinical bone marrow transplantation.

Chair:

Mohandas��Narla,��DSc
New York Blood Center
New York,��NY

Speaker:

Sean J.��Morrison,��PhD
University of Texas Southwestern Medical Center
Dallas,��TX
Hematopoietic Stem Cell Maintenance

Ernest Beutler Lecture and Prize

Controlling Hemoglobin Genes and Curing the Hemoglobin Disorders

Studies of hemoglobin, and its associated disorders, sickle cell disease (SCD) and the thalassemias, have written much of the history of the development of molecular biology and genetic medicine. More than 70 years ago, Dr. Linus Pauling dubbed SCD the first “molecular disease,” and seven years later Dr. Vernon Ingram identified the single amino acid difference between normal and sickle hemoglobin within the adult b-globin protein. With the advent of gene cloning and DNA sequencing, subsequent research in the 1980s elucidated the myriad mutations in the b-globin gene causing reduced or absent b-globin production in b-thalassemias. The benefits of increased expression of fetal hemoglobin (HbF) in individuals with SCD or b-thalassemia were recognized by astute clinicians based on of the lack of symptoms in the neonatal period and in the benign hereditary persistence of fetal hemoglobin (HPFH) condition. This stimulated interest in understanding the intricacies of globin gene regulation and how the switch from fetal (g)-to adult (b)-globin is normally controlled. In parallel, advances in gene transfer fueled efforts to introduce normal globin genes into hematopoietic stem cells of patients with mutant b-globin genes as curative therapy, an autologous approach built on decades of improvements in allogeneic bone marrow transplantation. Finally, remarkable advances in the modification of genes with CRISPR over the past decade have provided the means to define with precision the function of specific DNA sequences and develop gene editing approaches for therapy.

These research threads have converged to bring the first successive clinical trials forward for patients with SCD and b-thalassemia. In the last year, both globin gene addition (lovo-cel) and CRISPR gene editing (exa-cel) therapies received FDA approval. This lecture will describe the background and results of these groundbreaking studies, and discuss the challenges faced in bringing therapies to the many patients with SCD and b-thalassemia, particularly in resource-limiting geographic regions.

Dr. Stuart Orkin will describe current perspectives on the transcriptional control of globin genes, focusing on the direct role of the repressor protein BCL11A in silencing of HbF production and how CRISPR editing of an erythroid enhancer within the BCL11A gene forms the basis of the approved editing therapy, exa-cel, developed by CRISPR Therapeutics and Vertex Pharmaceuticals.

Dr. John Tisdale will summarize recent advances in ex vivo modification of hematopoietic stem cells for both lentiviral gene and CRISPR gene editing therapies for the hemoglobin disorders, concentrating on clinical parameters and prospects for improving preconditioning and moving toward strategies that would allow application without the need for hospitalization and intensive supportive care.

Chair:

Mohandas��Narla,��DSc
New York Blood Center
New York,��NY

Speakers:

Stuart H��Orkin,��MD
Harvard Medical School
Boston,��MA
Basic Science

John��Tisdale,��MD
National Institutes of Health
Bethesda,��MD
Clinical/Translational Science