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 language | English |
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Pages (from-to) | 165-173 |
Number of pages | 9 |
Journal | Clinical Cancer Research |
Volume | 29 |
Issue number | 1 |
DOIs | |
State | Published - 4 Jan 2023 |
Externally published | Yes |
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.
Funders | Funder number |
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American Society for Hematology | |
Long Island Sound Chapter | |
National Institute on Aging | P01-AG052359 |
National Heart, Lung, and Blood Institute | R01-HL123340, R01-HL147584 |
National Cancer Institute | P01-CA023766, R01-CA228308, P30 CA008748, R01-CA228358 |
National Institute of Allergy and Infectious Diseases | K08HL143189, 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 |