Conditioning regimens are associated with distinct patterns of microbiota injury in allogeneic hematopoietic cell transplantation Journal Article
| Authors: | Shouval, R.; Waters, N. R.; Gomes, A. L. C.; Zuanelli Brambilla, C.; Fei, T.; Devlin, S. M.; Nguyen, C. L.; Markey, K. A.; Dai, A.; Slingerland, J. B.; Clurman, A. G.; Fontana, E.; Amoretti, L. A.; Wright, R. J.; Hohl, T. M.; Taur, Y.; Sung, A. D.; Weber, D.; Hashimoto, D.; Teshima, T.; Chao, N. J.; Holler, E.; Scordo, M.; Giralt, S. A.; Perales, M. A.; Peled, J. U.; van den Brink, M. R. M. |
| Article Title: | Conditioning regimens are associated with distinct patterns of microbiota injury in allogeneic hematopoietic cell transplantation |
| Abstract: | 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 α-diversity. RESULTS: We identified distinct patterns of microbiota injury that varied by conditioning regimen. Diversity loss was graded into three levels of conditioning-associated microbiota injury (CMBI) in a multivariable model that included antibiotic exposures. High-intensity regimens, such as total body irradiation (TBI)-thiotepa-cyclophosphamide, 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. ©2022 American Association for Cancer Research. |
| Keywords: | retrospective studies; transplantation, homologous; cyclophosphamide; hematopoietic stem cell transplantation; retrospective study; graft versus host reaction; transplantation conditioning; graft vs host disease; rna 16s; allotransplantation; adverse event; microflora; microbiota; rna, ribosomal, 16s; humans; human |
| Journal Title: | Clinical Cancer Research |
| Volume: | 29 |
| Issue: | 1 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2023-01-01 |
| Start Page: | 165 |
| End Page: | 173 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-22-1254 |
| PUBMED: | 36322005 |
| PROVIDER: | scopus |
| PMCID: | PMC9812902 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Jonathan U. Peled -- Source: Scopus |
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