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Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation
Jonathan U Peled1, Sean M Devlin1, Anna Staffas1
1Jonathan U. Peled, Sean M. Devlin, Anna Staffas, Melissa Lumish, Raya Khanin, Eric R. Littmann, Lilan Ling, Satyajit Kosuri, Molly Maloy, John B. Slingerland, Katya F. Ahr, Kori A. Porosnicu Rodriguez, Yusuke Shono, Ann E. Slingerland, Melissa D. Docampo, Boglarka Gyurkocza, Doris M. Ponce, Juliet N. Barker, Miguel-Angel Perales, Sergio A. Giralt, Ying Taur, Eric G. Pamer, Robert R. Jenq, and Marcel R.M. van den Brink, Memorial Sloan Kettering Cancer Center; Jonathan U. Peled, Melissa D. Docampo, Boglarka Gyurkocza, Doris M. Ponce, Juliet N. Barker, Miguel-Angel Perales, Sergio A. Giralt, Ying Taur, Eric G. Pamer, Robert R. Jenq, and Marcel R.M. van den Brink, Weill Cornell Medical College; Melissa Lumish, New York University Langone Medical Center, New York, NY; Anthony D. Sung, Duke University Medical Center, Durham, NC; Daniela Weber, University Medical Center, Regensburg, Germany; and Amin M. Alousi, University of Texas MD Anderson Cancer Center, Houston, TX.
Certain gut bacteria, like Eubacterium limosum, may reduce relapse risk after allogeneic hematopoietic-cell transplantation (allo-HCT). Higher abundance of these bacteria is linked to lower relapse rates, suggesting potential therapeutic targets for improving survival post-transplant.
Area of Science:
- Microbiome research
- Hematopoietic-cell transplantation
- Immunology
Background:
- Allogeneic hematopoietic-cell transplantation (allo-HCT) survival is limited by relapse, graft-versus-host disease (GVHD), and infection.
- Intestinal microbiota alterations are linked to GVHD, bacteremia, and reduced survival post-allo-HCT.
- Gut bacteria influence systemic immunity, including anti-tumor responses, prompting investigation into their role in allo-HCT relapse.
Purpose of the Study:
- To investigate the association between intestinal microbiota composition and relapse/progression of disease after allo-HCT.
- To identify specific bacterial species or groups that may predict or influence relapse risk.
Main Methods:
- Profiling the intestinal microbiota of 541 patients undergoing allo-HCT using 16S ribosomal sequencing of stool samples.
- Analyzing the relationship between bacterial abundance and relapse/progression over 2 years using cause-specific proportional hazards models.
- Employing a retrospective discovery-validation cohort study design.
Main Results:
- Higher abundance of a bacterial group, primarily Eubacterium limosum, was significantly associated with a decreased risk of relapse/progression (HR 0.82; P=.009).
- Patients with this bacterial group had a lower 2-year cumulative incidence of relapse/progression (19.8%) compared to those without (33.8%).
- These associations remained significant in multivariable analyses and were most pronounced in recipients of T-cell-replete allografts.
Conclusions:
- Specific intestinal bacteria, particularly Eubacterium limosum, are associated with reduced relapse risk after allo-HCT.
- These bacteria may serve as potential biomarkers for predicting relapse.
- Targeting these gut bacteria could represent a novel therapeutic strategy to prevent relapse and enhance survival post-allo-HCT.
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