Scientific Spotlight Sessions

Bridging Translational Science and Clinical Trials to Transform Burkitt Lymphoma Research Globally

Monday, December 8, 2025, 10:30 a.m. - 11:45 a.m.
OCCC - Tangerine Ballroom F2

The treatment of Burkitt’s lymphoma (BL) is a testament to the profound curative potential of combination chemotherapy, and most patients are cured with modern treatment approaches that utilize intensive chemotherapy along with aggressive supportive care. Still, gaps remain for patients unable to tolerate intensive chemotherapy, for those with disease that become resistant to chemotherapy, and for those who live in areas of the world with fewer supportive care resources.  This session will examine the current understanding of the molecular biology of BL, the tumor microenvironment and how this might influence clinical and translational research efforts.  It will also explore and highlight significant efforts in Sub-Saharan Africa that attempt to bridge the gap and improve outcomes globally.

Dr. Mark Roschewski will describe the history of BL and its emergence as one of the most sensitive subtypes of lymphoma to chemotherapy.  More recently, the field has come to understand molecular subtypes of BL that may have differential response to immunotherapy and/or targeted agents.  Dr. Roschewski will also address the role of the tumor microenvironment and its relevance in clinical outcomes. 

Dr. Clara Chamba will present progress from the Aggressive Infection-Related East African Lymphoma (AI-REAL) study, focusing on innovative approaches to diagnosing and managing BL in Sub-Saharan Africa. She will highlight minimally invasive diagnostic strategies, share key insights from recent validation efforts, and discuss lessons learned in building sustainable capacity for lymphoma care in resource-limited settings. Dr. Chamba will also reflect on the collaborative model that brought together international partners and local institutions to address diagnostic delays. Finally, she will outline the broader implications of this work for advancing equitable access to timely cancer diagnosis across low- and middle-income countries.

Speakers:

Mark Roschewski, MD
NIH/NIC
Translating Knowledge about Burkitt Lymphoma Genomics and Microenvironment into Novel Clinical Trials

Clara Chamba, MD
Muhimbili University of Health and Allied Sciences
Burkitt Lymphoma Research in Africa: Overcoming Challenges and Unlocking Translational Potential

Creative and Novel Statistical Techniques to Design and Analyze Data for Trials Focused on Rare Hematologic Diseases

Monday, December 8, 2025, 10:30 a.m. - 11:45 a.m.
Hyatt - Regency Ballroom R

Clinical trials in rare hematologic conditions often face significant hurdles: limited patient populations, disease heterogeneity, and complex endpoints, further compounded by regulatory and ethical considerations.  Join us for an interactive discussion on how innovative statistical methods can improve trial feasibility and scientific rigor while navigating the constraints inherent in rare disease research. Practical, impactful designs and analysis strategies will be explored through real-world trial applications, with lessons that extend beyond statistics to inform clinical decision-making.  This session marks the first statistics-focused event during the ASH Annual Meeting — Where Clinical Insight Meets Statistical Innovation. It will provide a unique platform for clinicians and statisticians to connect, share knowledge, and collaborate on innovative ideas for trials focused on rare hematologic diseases.

Dr. Arzu Onar-Thomas will provide an overview of trial design challenges encountered in rare disease settings. She will discuss how leveraging external data can optimize trial design while balancing necessary trade-offs, with a focus on the strategies on interim futility analyses for single-arm trials.  Motivating examples from recently completed pediatric brain tumor trials will be discussed, highlighting the approaches which are readily applicable for rare heme disease trials.  

Dr. Ernest Amankwah will discuss a novel adaptation of the parallel cohort randomized controlled trial that recaptures eligible participants who would have been excluded from a trial otherwise.  He will outline approaches employed to assure congruence of this non-randomized control group, and present the application of this adaptation in the CRITICAL-Kids-TP trial, a proposed phase 3 trial of pharmacological thromboprophylaxis versus standard of care (no pharmacological thromboprophylaxis) in critically ill adolescents.

Chair:

Fangxin Hong
Pfizer Inc

Speakers:

Arzu Onar-Thomas
St Jude's Children Hospital
Rational Compromises in Trial Design for Rare Diseases - Lessons from Pediatric Cancer

Ernest Amankwah
Johns Hopkins University School of Medicine
Design and Application of RCT for Rare/Low-Frequency Diseases: From Traditional Parallel-Cohort to Novel Contemporaneous Control Recapture

Epigenomic Frontiers in the Diagnosis of Hematological Malignancies

Monday, December 8, 2025, 2:45 p.m. - 4:00 p.m.
OCCC - W230

The rapid and accurate diagnosis of acute leukemias remains a major challenge in hematopathology. Traditional diagnostic methods often fall short in delivering timely and precise classification, which is essential for effective treatment planning. Recent advances in next- and third-generation sequencing technologies have transformed our ability to decode nucleotide sequences and epigenetic modifications, including chromatin accessibility and DNA methylation. These technologies offer a promising path toward improving both the speed and accuracy of leukemia diagnostics. By integrating long-read sequencing and chromatin profiling, researchers can now classify leukemias with unprecedented precision. These innovative approaches not only deepen our understanding of the molecular basis of hematologic malignancies but are also entering clinical evaluation. This session will showcase cutting-edge developments in epigenomic and chromatin-based diagnostics for acute leukemia.

Dr. Volker Hovestadt will discuss a novel artificial intelligence tool called MARLIN that can quickly and accurately classify molecular subtypes of acute leukemia. This new tool applies DNA methylation profiling to distinguish 38 different leukemia subtypes across age groups and myeloid and lymphoid lineages. Real-time MARLIN predictions generate accurate predictions in as little as two hours of sample receipt, potentially helping doctors make faster and more precise treatment decisions for patients with suspected acute leukemia.

Dr. Florence Nguyen-Khac will discuss the value of DNA methylation profiling in three examples of mature B-cell malignancies: Chronic Lymphocytic Leukemia, Waldenström’s Macroglobulinemia, and B-Prolymphocytic Leukemia. Her presentation will explore how epigenetic profiling, particularly DNA methylation patterns, can improve disease classification, refine prognosis, and guide therapeutic strategies in these closely related hematologic disorders.

Chair:

Bert Van der Reijden, PhD
Radboudumc

Speakers:

Volker Hovestadt, PhD
Dana-Farber Cancer Institute
Long-Read Epigenomic Classification of Acute Leukemia

Florence Nguyen-Khac
Hopital Pitie-Salpetriere, Sorbonne Universite
Chromatin-Based Diagnosis in Lymphocytic Leukemia

The Issue of Rejection of Allogeneic Cellular Therapies: Evidence, Mechanisms, and Novel Strategies to Overcome It

Sunday, December 7, 2025, 4:30 p.m. - 5:45 p.m.
OCCC - Sunburst Room (W340)

Allogeneic cellular therapies are emerging as a transformative platform for cancer treatment, offering immediate availability and broader access compared with autologous therapies that require individualized manufacturing. However, the success of off-the-shelf approaches is limited by immune rejection, as both the adaptive and innate arms of the host immune system rapidly recognize and eliminate donor-derived cells. Rejection can occur through T-cell–mediated recognition of mismatched major histocompatibility complex (MHC) molecules, antibody-driven responses, natural killer (NK) cell–mediated cytotoxicity, and macrophage-mediated clearance. These immune barriers lead to poor persistence of allogeneic products and reduced therapeutic efficacy.

This session will highlight cutting-edge research dissecting the immunologic mechanisms that lead to failure of allogeneic cell therapies and emerging engineering and therapeutic strategies designed to overcome rejection. It will also emphasize the convergence of new genome editing technologies, immune evasion strategies, and advances in cell manufacturing that together are redefining what is possible for off-the-shelf cellular immunotherapy.

Dr. Marco Ruella will review clinical data demonstrating failure of allogeneic cell therapies due to immune-mediated clearance and will delineate key pathways, both innate and adaptive, responsible for allogeneic cell rejection. He will highlight evidence from early-phase clinical trials and discuss how immune profiling can uncover rejection mechanisms that limit persistence and durability.

Dr. May Daher will discuss next-generation strategies aimed at reducing immune rejection of allogeneic products. These approaches include eliminating MHC expression, inserting immune checkpoint ligands, modulating NK-cell activation pathways, and incorporating immune cloaking elements such as CD47 expression. She will also address how combinatorial genome engineering and pharmacologic modulation are enabling increasingly resilient cellular products capable of sustained antitumor responses.

Speakers:

Marco Ruella, MD
University of Pennsylvania
Current Clinical Evidence of Allogeneic Cellular Products Failure and Mechanisms

May Daher, MD
MD Anderson Cancer Center
Strategies to Reduce Immune Rejection of Off-the-Shelf Cell Therapies

Transcending Boundaries: Study of Ambiguous Lineage Acute Leukemia Unlocks Mysteries for All Leukemias

Monday, December 8, 2025, 4:30 p.m. - 5:45 p.m.
OCCC - W224CDGH

The existence of acute leukemias of mixed or ambiguous lineage has long been recognized but the diagnostic criteria for mixed phenotype acute leukemia (MPAL) has been historically fluid. This fluidity reflects the heterogeneous nature of this entity, which unlike other acute leukemias, largely lacks defining genetic lesions and relies on immunophenotypic criteria for diagnosis, though more recent diagnostic criteria incorporate a limited number of genetic abnormalities. This lack of disease-defining genetics further underscores a dearth of understanding for molecular mechanisms driving pathophysiology. Furthermore, shifting diagnostic criteria and disease heterogeneity make clinical studies of this rare disease challenging, presenting major barriers to refining treatment to optimize clinical outcomes. This session will discuss the phenomenon of ambiguous lineage acute leukemia as a spectrum encompassing multiple leukemia subtypes that are characterized by retained differentiation potential and lineage plasticity.

Dr. Ruud Delwel will discuss how leukemias that were initially uncovered as acute myeloid leukemias (AML) appeared to be clearly distinct based on unique DNA methylation profiles. These leukemias exhibit hybrid myeloid/lymphoid epigenetic landscapes. DNA methylation reveals similarity with early T-cell precursor acute lymphoblastic leukemias, whereas histone acetylation signatures are more in line with profiles uncovered in AML, in particular with cases that carry CEBPA mutations. Dr. Delwel will discuss the role of epigenetic dysregulation as the basis of malignant development of these leukemias with ambiguous lineage.

Dr. Catherine Smith will discuss MPAL as a stem cell-like leukemia, focusing on multiomic single cell sequencing studies of MPAL which reveal a shared stem cell-like transcriptional profile indicative of high differentiation potential and independent of underlying genetic abnormalities. She will describe MPAL95, a gene set score established from genes highly enriched in the most stem-like MPAL cells, which is applicable to bulk RNA sequencing data and is predictive of survival in adult and pediatric MPAL patient cohorts.

Speakers:

Ruud Delwel
Erasmus MC Cancer Institute and Oncode Institute
Epigenetic Dysregulation Drives Mixed Phenotype Acute Leukemia

Catherine Smith, MD
University of California, San Francisco
Multi-omic Analysis Reveals the Heterogeneity and Stem Cell Origin of Acute Leukemia of Ambiguous Lineage/Mixed Phenotype Acute Leukemia