Abstract: The 63rd American Society of Hematology (ASH) Annual Meeting and Exposition is back to meeting in person! This year, it will be held December 11-14, 2021, at the Georgia World Congress Center in Atlanta. However, the virtual exhibit hall will still be available during the meeting for virtual attendees to access to thousands of scientific abstracts highlighting cutting-edge research in hematology. Proof of vaccination will be required for all those attending in-person. This conference event is an opportunity to enhance your practice through educational programs while exploring new research presented by hematologists around the world. Check out highlights from the upcoming conference to help you make the most of your time learning about new research and reconnecting with colleagues at ASH. Preview Day (Virtual Only) Wednesday, December 8 at 9 a.m. and all day December 9 While some ASH attendees may already be familiar with the virtual conference platform, ASH is offering Preview Day as an opportunity to participate in an orientation of the virtual meeting platform and become familiar with its features and navigation. There will also be the opportunity to preview some of the pre-recorded presentations that are part of the Education Program and Scientific Program sessions, though not presentations subject to embargo. ASH-a-Palooza Friday, December 10, 12:30 p.m. to 5:00 p.m. At ASH-a-Palooza, attendees will have the opportunity to participate in an educational experience that will offer micro-learning sessions and mentorship opportunities. The event will include several interactive learning opportunities, including rapid-fire learning sessions (Blood Drops) that will allow the audience to move easily between each presentation. NEW! Welcome Back Reception (In-Person) Friday, December 10, 6 p.m. to 8 p.m. To celebrate the return to an in-person meeting after COVID-19 quarantine, ASH is hosting a reunion-style reception for all participants to meet up and get re-acquainted. The informal reception will allow participants to drop in after picking up their registration badge and visit with colleagues for a while either before or after attending ASH-a-Palooza, Scientific Workshops, Satellite Symposia, or going with colleagues for dinner at one of Atlanta's wonderful restaurants. Enjoy catching up with your friends and colleagues, or meet new ones at this special and additional networking opportunity at the ASH annual meeting. Program Details Attendees will have a plethora of scientific and educational programs at their disposal. Aberrant Transcriptional Regulation In Development and Malignancies Scientific Committee on Epigenetics and Genomics This session will focus on mechanisms of altered gene expression driving malignant transformation. Chromosomal translocations that result in gene fusions are one of the earliest recognized oncogenic events leading to transformation. However, aberrant gene expression involving promoter to enhancer alterations, caused by chromosomal translocations and de novo mutations, have been reported. Understanding the mechanisms of altered gene expression, including the role of transcriptional regulators, may lead to the discovery of drugs that interfere with defective transcriptional control. Dr. Marc Mansour will specifically discuss mechanisms of oncogene activation in T-ALL, whereby somatic mutations in non-coding regions near an oncogene can create active regulatory elements. Dr. Kathrin Bernt will give an overview of types of fusion in leukemia and describe in detail rearrangements that result in aberrant gene regulation as the key outcome. Dr. Jolanta Grembecka will discuss how insight into the mechanisms of transcriptional control may lead to the discovery of new promising drugs. AI, Data Science, Computer Vision and the Hematology Laboratory of the Future Scientific Committee on Hematopathology & Clinical Laboratory Hematology This session includes speakers who are at the forefront of developing and applying computational approaches for the quantitative analysis of tissue and liquid biopsy samples. Dr. Yinyin Yuan will discuss her group's discoveries in the geospatial organization of the tumor microenvironment and its implications for pathological analysis of tissue samples in the future. Dr. Metin Gurcan will discuss his experience in using digital images captured with whole-slide scanners to implement AI technology to large datasets. Dr. David Jaye will discuss the current state of the art in computer vision and AI use, as well as the expectations and challenges faced by hematologists and hematopathologists in applying these new technologies for routine clinical care. Cellular Memory and Innate Immune Pathways During Myeloid Cell Development and Infection Scientific Committee on Myeloid Biology Innate myeloid hematopoietic cells have recently been recognized as retaining the memory of an initial immunological challenge to adapt their responses to secondary challenges. This session will highlight recent cutting-edge research dissecting mechanisms of trained immunity as well as how these pathways can contribute to myeloid cell development. Dr. Mihai Netea will introduce the concept of trained immunity and discuss the metabolic changes that take place in the trained innate immune cells after infections and vaccinations, leading to an improved host defense. Dr. Sandrine Sarrazin will present new findings on how hematopoietic stem cells (HSCs) can directly sense cytokines and pathogen-associated molecular patterns such as toll-like receptor ligands conferring an innate immune memory. Dr. Eirini Trompouki will review how transposable elements can induce innate immune signaling for hematopoietic stem cell development and regeneration, with impacts on HSC aging and trained immunity. Immune Evasion and Immunotherapy in Myeloid Malignancies Scientific Committee on Myeloid Neoplasia To highlight the potential of immunotherapy, this session will cover our current understanding of immune dysregulation and novel immunotherapy approaches in myeloid malignancies. Dr. Sergio Rutella will discuss mechanisms of immune evasion with a focus on acute myeloid leukemia. Dr. Johanna Olweus will illuminate how T cells in allo-HSCT grafts can mediate cures in myeloid leukemia, and how anti-leukemic T-cell receptors can be selected from healthy donor T-cell repertoires. Dr. Saar Gill will discuss the interactions between myeloid malignancies and the surrounding residual normal hematopoiesis in the context of antigen-specific immunotherapies. Molecular Basis of Disease Progression in Plasma Cell Precursor Diseases Scientific Committee on Myeloid Neoplasia Multiple myeloma and related plasma cell disorders are typically preceded by an asymptomatic precursor phase, monoclonal gammopathy of undetermined significance (MGUS), and in some individuals an intervening phase termed smoldering multiple myeloma (SMM). This session will highlight the progress made in recent years that will enable us to develop effective prevention and treatment strategies with a real potential for cure in some patients. Dr. Giada Bianchi will discuss the role the bone marrow niche plays in the progression of precursor plasma cell disorders, MGUS, and SMM to active multiple myeloma. Dr. Niccolo Bolli will review novel acquisition in genomics of myeloma and its related asymptomatic precursor diseases. Dr. Sigurdur Kristinsson will discuss the role of early detection and intervention in multiple myeloma. Novel Findings in CAR-T Cell Therapies for Hematologic Malignancies Scientific Committee on Transplantation Biology and Cellular Therapies This session will highlight recent cutting-edge research in CAR-T cell design and downstream effects, as well as real-world mechanisms of resistance and approaches to next-generation CAR-T cell therapeutics. Dr. Marcela Maus will discuss the mechanisms underlying CAR-T cell function as driven by differences in co-stimulation, antigen binding, signaling, transcriptional profiling, and T-cell effector functions. Dr. David Baker will focus on synthetic biology, including synthetic genes, novel “from-scratch” protein design, and advances in deep learning-based structure modeling. Dr. Marco Ruella will discuss recent findings on mechanisms leading to failure of CAR-T cell immunotherapy in B-cell leukemia and lymphoma patients. Regulators of Hematopoietic Stem Cell Development and Expansion: Bench to Bedside A low stem cell dose and lack of human leukocyte antigen-matched donors are major barriers to hematopoietic stem cell (HSC) transplantation and gene therapies. This session will highlight recent advances in the understanding of regulators of HSC development and self-renewal along with therapeutic application of expanded HSCs. Dr. Hanna Mikkola will discuss mechanisms that regulate the generation of self-renewing HSCs during human development and elucidate how single-cell and spatial transcriptomic approaches have illuminated this process. Dr. Sauvageau will discuss the issue of hematopoietic stem cell expansion with a focus on the small molecule and gene regulators of self-renewal, which have potential applications in the clinical arena. Dr. Yamazaki will highlight recent technological advances in expansion of mouse and human HSCs. Scientific Spotlight Sessions Human Pluripotent Stem Cell-Derived Hematopoiesis: From Development to Stem Cell Therapies Of Lineage and Legacy: Applications of Lineage Tracing In Hematology Education Spotlight Sessions Approved, But Should We Use It?—Are The New Trial Designs Effective? Financial Stewardship in an Era of Hematologic Advances In Care: Whose Value? What Price? Genetic Testing for Von Willebrand Disease The Ups and Downs of Therapy For Children With Trisomy 21 and Acute Leukemia Continuing Conversations With the Speakers On Challenges in Cell Therapy: Relapse and Toxicities On Getting the Most From Minimal Residual On Gut Microbiome and The Endothelium On RNA In Normal and Malignant Hematopoiesis Highlights from the Educational Sessions On Malignant Hematology ALL: New Directions for Adult Patients Dr. Noelle Frey will discuss outcomes of CAR-T cell therapy with a focus on both clinical responses and toxicity. Dr. Marlise Luskin will discuss the specific challenges of treating older adults with ALL with conventional chemotherapy. Dr. Nicola Goekbuget will discuss approaches for assessing and interpreting MRD in ALL including pros and cons of various strategies. AML: So Many Options, So Little Time Dr. Felicitas Thol will outline recent developments in the treatment of newly diagnosed AML. Dr. Christian Thiede will focus his discussion on the use of maintenance therapies following induction and consolidation therapy. Dr. Margaret Kasner will address which patient populations are likely to benefit from the recently approved and novel investigational agents. Challenges in Multiple Myeloma Treatment Dr. Maria-Victoria Mateos will discuss how to identify and manage high-risk Myeloma patients. Dr. Ashley Rosko will outline how to incorporate frailty assessments in the evaluation of older adults with multiple myeloma in the clinical setting with consideration of other factors such as patient preferences, treatment risks/benefits, life expectancy, and disease biology. Dr. Noopur Raje will address the improvements in multiple myeloma therapy through the achievement of deep responses that are beyond the limit of detection of historical immunohistochemistry and conventional flow cytometry, such as next generation flow cytometry and sequencing for assessing minimal residual disease. CLL: Extending Survival Professor Constantin Tam will discuss the benefits and limitations of continuous therapy in patients with CLL. Professor Florence Cymbalista will discuss the opportunities and challenges of time limited frontline treatment in CLL. Dr. Deborah Stephans will cover the use of anti-CD20 monoclonal antibody combination therapies in patients with CLL. CML: Success Breeds More Success Dr. Andreas Hochhaus will discuss TKI discontinuation and strategies to increase the number of eligible patients. Dr. Michael Mauro will discuss lifelong TKI therapy, including management of cardiovascular risk factors and other toxicities. Dr. Gabriela Hobbs will discuss advanced phase CML and the management of accelerated and blast phase disease. Defeating Diffuse, Double-Hit and Dogged Non-Hodgkin Lymphoma Dr. Kieron Dunleavy will discuss the challenges and controversies of up-front and later therapy selection in “double-hit” and other high-grade B-cell lymphomas. Dr. Bjorn Chapuy will focus on recent advances in the understanding of the molecular heterogeneity of diffuse large B-cell lymphoma. Dr. Reem Karmali will outline the strengths and limitations of CD19 CARTs as customized engineered products versus off-the-shelf immunotherapies such as bispecific CD20-CD3 antibodies as therapeutic options for relapsed/refractory aggressive B-cell non-Hodgkin lymphomas. Hodgkin Lymphoma: Cure and Optimal Survivorship Dr. Kristie Blum will review several of the ongoing controversies regarding the use of chemotherapy, radiation, and PET-directed therapy in patients with previously untreated early-stage Hodgkin lymphoma. Dr. Marie Jose Kersten will discuss salvage therapy options for patients who relapse after frontline therapy for Hodgkin lymphoma. Dr. Mehdi Hamadani will discuss the challenging subset of classical Hodgkin lymphoma patients with disease refractory to both brentuximab vedotin and checkpoint inhibitors (double refractory patients). How Can We Ensure That Everyone Who Needs A Transplant Can Get One? Dr. Andrew Artz will discuss emerging data on the use and outcomes of alloHCT among older patients. Dr. Vanderson Rocha will describe an international perspective on global growth of allotransplant related to demographics, socioeconomic factors, and providers and health care systems. Dr. Navneet Majhail will outline a United States perspective on alloHCT access. Immunology 101: What the Practicing Hematologist Needs to Know Dr. Shannon Carty will give a general overview of the immune system and the complex interplay between its cellular components, as well as what constitutes a typical immune response. Dr. Sung-Yun Pai will highlight how immunodeficiencies, both inherited and acquired, can lead to malignancy. Dr. Nathan Singh will detail the use of modified T cells as therapeutic agents in cancer and viral infections. What are the factors that guide treatment selection in mycosis fungoides (MF) and Sézary syndrome (SS)? In this series, Dr. Carla Casulo will discuss patient and tumor-specific factors associated with risk of disease progression, histologic transformation, and premature death from follicular lymphoma. Dr. Youn Kim will review the disease heterogeneity and the unique quality of life issues in patients with mycosis fungoides and Sézary syndrome, the major subtypes of cutaneous T-cell lymphoma. Dr. Robin Foà will cover the possible role of MRD in the management of patients with indolent NHL, focusing in particular on follicular lymphoma. It Takes a Village: Maximizing Supportive Care and Minimizing Toxicity During Childhood Leukemia Therapy Dr. Brian Fisher will discuss an evidence-based approach to antifungal prophylaxis and empirical therapy during periods of neutropenia in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Dr. Kasey Leger will review the impact of cardiotoxicity in children with AML and highlight opportunities for cardioprotection during AML therapy. Dr. Deepa Bhojwani will focus on common central nervous system toxicities during chemotherapy and immunotherapy for childhood ALL.