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

Publication ,  Journal Article
Shouval, R; Waters, NR; Gomes, ALC; Zuanelli Brambilla, C; Fei, T; Devlin, SM; Nguyen, CL; Markey, KA; Dai, A; Slingerland, JB; Clurman, AG ...
Published in: Clin Cancer Res
January 4, 2023

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.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

January 4, 2023

Volume

29

Issue

1

Start / End Page

165 / 173

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Transplantation Conditioning
  • Retrospective Studies
  • RNA, Ribosomal, 16S
  • Oncology & Carcinogenesis
  • Microbiota
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Graft vs Host Disease
  • Cyclophosphamide
 

Citation

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Shouval, R., Waters, N. R., Gomes, A. L. C., Zuanelli Brambilla, C., Fei, T., Devlin, S. M., … van den Brink, M. R. M. (2023). Conditioning Regimens are Associated with Distinct Patterns of Microbiota Injury in Allogeneic Hematopoietic Cell Transplantation. Clin Cancer Res, 29(1), 165–173. https://doi.org/10.1158/1078-0432.CCR-22-1254
Shouval, Roni, Nicholas R. Waters, Antonio L. C. Gomes, Corrado Zuanelli Brambilla, Teng Fei, Sean M. Devlin, Chi L. Nguyen, et al. “Conditioning Regimens are Associated with Distinct Patterns of Microbiota Injury in Allogeneic Hematopoietic Cell Transplantation.Clin Cancer Res 29, no. 1 (January 4, 2023): 165–73. https://doi.org/10.1158/1078-0432.CCR-22-1254.
Shouval R, Waters NR, Gomes ALC, Zuanelli Brambilla C, Fei T, Devlin SM, et al. Conditioning Regimens are Associated with Distinct Patterns of Microbiota Injury in Allogeneic Hematopoietic Cell Transplantation. Clin Cancer Res. 2023 Jan 4;29(1):165–73.
Shouval, Roni, et al. “Conditioning Regimens are Associated with Distinct Patterns of Microbiota Injury in Allogeneic Hematopoietic Cell Transplantation.Clin Cancer Res, vol. 29, no. 1, Jan. 2023, pp. 165–73. Pubmed, doi:10.1158/1078-0432.CCR-22-1254.
Shouval R, Waters NR, Gomes ALC, Zuanelli Brambilla C, Fei T, Devlin SM, Nguyen CL, Markey KA, Dai A, Slingerland JB, Clurman AG, Fontana E, Amoretti LA, Wright RJ, Hohl TM, Taur Y, Sung AD, Weber D, Hashimoto D, Teshima T, Chao NJ, Holler E, Scordo M, Giralt SA, Perales M-A, Peled JU, van den Brink MRM. Conditioning Regimens are Associated with Distinct Patterns of Microbiota Injury in Allogeneic Hematopoietic Cell Transplantation. Clin Cancer Res. 2023 Jan 4;29(1):165–173.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

January 4, 2023

Volume

29

Issue

1

Start / End Page

165 / 173

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Transplantation Conditioning
  • Retrospective Studies
  • RNA, Ribosomal, 16S
  • Oncology & Carcinogenesis
  • Microbiota
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Graft vs Host Disease
  • Cyclophosphamide