Scientific Spotlight Sessions

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

Burkitt lymphoma (BL) is an ultra-aggressive B-cell lymphoma with significant global disparities in outcomes, particularly in low-resource regions such as Central Africa and South America. Its rarity and rapid clinical course pose unique challenges for translational and clinical research. Historically, BL treatment has relied on adaptations of intensive chemotherapy, with little consideration for molecular and genomic features. Additionally, BL patients have been excluded from trials of immune-based therapies that have revolutionized the treatment of other aggressive B-cell lymphomas. Recent breakthroughs in BL genomics, tumor microenvironment research, and global collaborative efforts have opened new avenues for targeted and immunotherapy-based strategies.

This session will review these advances and their implications for future research. The first talk will focus on recent insights into BL biology, including genomics, immune microenvironment features, and emerging molecular targets in the context of upcoming clinical trials incorporating adoptive immunotherapy in this disease. The second talk will highlight advances and challenges in translational and clinical research in Africa and other low-resource settings, covering recent pediatric BL studies, low-cost molecular diagnostics, and vaccination initiatives. 

Speakers:

Mark Roschewski, MD
Center for Cancer Research, National Cancer Institute, NIH
Bethesda, MD, United States
Translating Knowledge about Burkitt Lymphoma Genomics and Microenvironment into Novel Clinical Trials

Clara Chamba
Muhimbili University of Health and Allied Sciences
Dar-es-Salaam, Tanzania
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

This session will highlight novel statistical methods and unique design and analysis considerations for clinical trials focused on rare hematologic diseases. It will provide a unique platform for interactive discussion and knowledge sharing on statistical design/analysis of clinical studies, for the clinical community.

Chair:

Fangxin Hong
Pfizer Inc
Cambridge, MA, United States

Speakers:

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

Ernest Amankwah
Johns Hopkins All Children's Hospital
St Petersburg, United States
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

The rapid and accurate diagnosis of acute leukemias remains a significant challenge in hematopathology. Traditional diagnostic methods often fall short in providing timely and precise classification, which is crucial for effective treatment planning. Recent advancements in next-generation and third-generation sequencing technologies have revolutionized our ability to read out nucleotide sequences and epigenetic modifications, such as chromatin accessibility and DNA methylation. These technologies offer a promising avenue for improving the diagnostic accuracy and speed for hematological malignancies.

By leveraging long-read sequencing and chromatin analysis, researchers are now able to classify leukemias more accurately and rapidly than ever before. These innovative approaches enhance our understanding of the molecular underpinnings of these malignancies and are entering evaluation in clinical trials.

This session will highlight cutting-edge developments in epigenomic and chromatin-based diagnostics.

Chair:

Bert Van der Reijden, PhD
Radboudumc
Nijmegen, Netherlands

Speakers:

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

Florence Nguyen-Khac
Centre de recherche des Cordeliers/INSERM1138
Paris, France
Chromatin-Based Diagnosis in Lymphocytic Leukemia

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

Allogeneic cell therapies offer significant advantages over autologous approaches, including reduced production times and broader accessibility for patients with rapidly progressing malignancies. However, immune rejection remains a critical challenge, as the host immune system often identifies and eliminates donor-derived cells through both adaptive and innate mechanisms. To address these barriers, researchers are developing innovative strategies such as genetic engineering to delete major histocompatibility complex molecules, overexpress immune checkpoint ligands, and disrupt key signaling pathways in innate immune cells. Additionally, immune cloaking techniques, like expressing CD47 to inhibit macrophage-mediated phagocytosis, and advancements in genome editing technologies, including CRISPR-Cas9, are being explored to enhance the persistence and efficacy of allogeneic cells.

This session will explore the breakthroughs aimed at overcoming immune rejection in allogeneic cell therapies.

Speakers:

Marco Ruella Jr, MD
Abramson Cancer Center
Philadelphia, PA, United States
Current Clinical Evidence of Allogeneic Cellular Products Failure and Mechanisms

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

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

The most recent 2022 World Health Organization and 2022 International Consensus Classification for myeloid neoplasms and acute leukemia each provided detailed descriptions of the current criteria for diagnosis of acute leukemia of ambiguous lineage and mixed phenotype acute leukemia. There have been large analyses of molecular data highlighting the breadth and heterogeneity of the individual patient samples, and literature defining the hematopoietic stem/progenitor cell as the cell of origin.

These analyses have led to new genes and pathways that can be targeted with therapeutic intent. This session will provide an overview of cell lineage leading to acute leukemias and will highlight possible novel targets.

Speakers:

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

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