Conditioning Regimens are Associated with Distinct Patterns of Microbiota Injury in Allogeneic Hematopoietic Cell Transplantation

Roni Shouval, Nicholas R. Waters, Antonio L.C. Gomes, Corrado Zuanelli Brambilla, Teng Fei, Sean M. Devlin, Chi L. Nguyen, Kate A. Markey, Anqi Dai, John B. Slingerland, Annelie G. Clurman, Emily Fontana, Luigi A. Amoretti, Roberta J. Wright, Tobias M. Hohl, Ying Taur, Anthony D. Sung, Daniela Weber, Daigo Hashimoto, Takanori TeshimaNelson J. Chao, Ernst Holler, Michael Scordo, Sergio A. Giralt, Miguel Angel Perales, Jonathan U. Peled, Marcel R.M. van den Brink

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

levels of conditioning-associated microbiota injury (CMBI) in a multivariable model that included antibiotic exposures. High-intensity regimens, such as total body irradiation (TBI)–thiotepacyclophosphamide, were associated with the greatest injury (CMBI III). In contrast, the nonmyeloablative regimen fludarabine–cyclophosphamide with low-dose TBI (Flu/Cy/TBI200) had a low-grade injury (CMBI I). The risk of acute GVHD correlated with CMBI degree. Pretransplant microbial compositions were best preserved with Flu/Cy/TBI200, whereas other regimens were associated with loss of commensal bacteria and expansion of Enterococcus. Conclusions: Our findings support an interaction between conditioning at the regimen level and the extent of microbiota injury.

Purpose: The gut microbiota is subject to multiple insults in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. We hypothesized that preparative conditioning regimens contribute to microbiota perturbation in allo-HCT. Experimental Design: This was a retrospective study that evaluated the relationship between conditioning regimens exposure in 1,188 allo-HCT recipients and the gut microbiome. Stool samples collected from 20 days before transplantation up to 30 days after were profiled using 16S rRNA sequencing. Microbiota injury was quantified by changes in a-diversity. Results: We identified distinct patterns of microbiota injury that varied by conditioning regimen.

Original languageEnglish
Pages (from-to)165-173
Number of pages9
JournalClinical Cancer Research
Volume29
Issue number1
DOIs
StatePublished - 4 Jan 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
©2022 American Association for Cancer Research.

Funding

This research was supported by NCI award numbers, R01-CA228358, R01-CA228308, P30 CA008748 MSK Cancer Center Support Grant/Core Grant and P01-CA023766; National Heart, Lung, and Blood Institute (NHLBI) award number R01-HL123340 and R01-HL147584; National Institute of Aging award number P01-AG052359; and Tri Institutional Stem Cell Initiative. Additional funding was received from The Lymphoma Foundation, The Susan and Peter Solomon Divisional Genomics Program, Cycle for Survival, and the Parker Institute for Cancer Immunotherapy. T.M. Hohl reports support from NIAID NIH Award R21AI156157. J.U. Peled reports funding from NHLBI NIH Award K08HL143189. K.A. Markey would like to acknowledge funding from the DKMS and American Society for Hematology, the Royal Australasian College of Physicians, The Haematology Society of Australia and New Zealand, and the American Australian Association. R. Shouval was supported by the American Society of Transplantation and Cellular Therapy New Investigator Award, the American Society of Hematology Fellow Scholar Award, a grant from the Long Island Sound Chapter, Swim Across America, the Robert Hirschhorn Award, and the Memorial Sloan Kettering Steven Greenberg Lymphoma Research Award.

FundersFunder number
American Society for Hematology
Long Island Sound Chapter
National Institute on AgingP01-AG052359
National Heart, Lung, and Blood InstituteR01-HL123340, R01-HL147584
National Cancer InstituteP01-CA023766, R01-CA228308, P30 CA008748, R01-CA228358
National Institute of Allergy and Infectious DiseasesK08HL143189, R21AI156157
American Society of Hematology
American Australian Association
Lymphoma Foundation
Parker Institute for Cancer Immunotherapy
American Society for Transplantation and Cellular Therapy
Swim Across America
Cycle for Survival
Royal Australasian College of Physicians
Haematology Society of Australia and New Zealand
DKMS Foundation

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