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Interrogating the Impact of the Intestinal Microbiome on Transplant and Cellular Therapies

PhD Trainee
Program: Scientific Symposia
Hematology Disease Topics & Pathways:
Bleeding and Clotting, Bleeding disorders, Sickle Cell Disease, Hemoglobinopathies, Diseases, Treatment Considerations, Biological therapies, Biological Processes, Maternal Health
Sunday, December 8, 2024: 9:30 AM-10:45 AM
Marriott Grand Ballroom 11-13 (Marriott Marquis San Diego Marina)
Chair:
Melody Smith, MD, MS, Stanford University School of Medicine
Disclosures:
Smith: A28 Therapeutics: Current holder of stock options in a privately-held company; CVS Caremark: Consultancy.

Alterations in the intestinal microbiome are linked to responses and outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) and chimeric antigen receptor (CAR) T-cell therapy. This session will highlight emerging research investigating the host-microbiome axis in this context. We will assess factors that alter the intestinal microbiome in recipients of these cellular therapies, including diet and antibiotic exposure. Further, we will evaluate interventions to modulate the microbiome in this setting, namely fecal microbiota transplant.

Dr. Malard will discuss the role of fecal microbiota transplant in hematological malignancies, focusing on allo-HCT. He will provide an overview of the available clinical data on fecal microbiota transplant for treating graft-versus-host disease after allo-HCT. Dr. Malard will also discuss the potential of this procedure to prevent graft-versus-host disease and mitigate infection. He will also address the role of fecal microbiota transplant as a strategy to eradicate multidrug-resistant bacteria in patients who have undergone allo-HCT. Finally, the potential mechanism of action of fecal microbiota transplant and the implications of fecal microbiota transplant for CAR-T will be discussed.

Dr. David will share an approach for using metagenomic sequencing of fecal samples to track dietary intake in recipients of allo-HCT. He will illustrate how this method, FoodSeq, was initially tested using hospital-based foods. Dr. David will also show how FoodSeq was applied to a patient population, revealing reductions in food intake after allo-HCT. Notably, he will also demonstrate how these changes in food intake were linked to aspects of patient outcomes and microbiome changes following allo-HCT.

Dr. Andermann will explore how antibiotics influence the gut microbiome, the antimicrobial resistome (the collection of resistance genes in the gut), and immunologic/infectious outcomes in patients undergoing allo-HCT and CAR-T. She will review previous research findings and describe how anaerobically active antibiotics alter taxonomic and resistance gene composition in the gut during allo-HCT. Additionally, she will compare the spectrum of activity of antibiotics commonly used for febrile neutropenia, emphasizing the need for further research on how these antibiotics distribute throughout the gut lumen and drive changes in the abundance of commensal gut bacteria in recipients of cellular therapy.

Florent Malard, M.D., Ph.D.

Sorbonne Université, Hôpital Saint-Antoine, AP-HP, Service d'Hématologie Clinique et Thérapie Cellulaire,Centre de Recherche Saint-Antoine UMRs938, Paris, France

Lawrence A David, PhD

Molecular Genetics & Microbiology, Duke University, Durham, NC

Tessa Andermann, MD, MPH

University of North Carolina, Chapel Hill, Chapel Hill, NC; Department of Medicine, Division of Infectious Diseases, UNC Chapel Hill, Chapel Hill, NC

See more of: Scientific Symposia