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Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.

Publication ,  Journal Article
Peled, JU; Gomes, ALC; Devlin, SM; Littmann, ER; Taur, Y; Sung, AD; Weber, D; Hashimoto, D; Slingerland, AE; Slingerland, JB; Maloy, M; Cho, C ...
Published in: N Engl J Med
February 27, 2020

BACKGROUND: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. METHODS: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death. RESULTS: We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival. CONCLUSIONS: Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

February 27, 2020

Volume

382

Issue

9

Start / End Page

822 / 834

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Survival Analysis
  • Prospective Studies
  • Prognosis
  • Middle Aged
  • Male
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • General & Internal Medicine
  • Gastrointestinal Microbiome
 

Citation

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Peled, J. U., Gomes, A. L. C., Devlin, S. M., Littmann, E. R., Taur, Y., Sung, A. D., … van den Brink, M. R. M. (2020). Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N Engl J Med, 382(9), 822–834. https://doi.org/10.1056/NEJMoa1900623
Peled, Jonathan U., Antonio L. C. Gomes, Sean M. Devlin, Eric R. Littmann, Ying Taur, Anthony D. Sung, Daniela Weber, et al. “Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.N Engl J Med 382, no. 9 (February 27, 2020): 822–34. https://doi.org/10.1056/NEJMoa1900623.
Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, Sung AD, et al. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N Engl J Med. 2020 Feb 27;382(9):822–34.
Peled, Jonathan U., et al. “Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.N Engl J Med, vol. 382, no. 9, Feb. 2020, pp. 822–34. Pubmed, doi:10.1056/NEJMoa1900623.
Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, Sung AD, Weber D, Hashimoto D, Slingerland AE, Slingerland JB, Maloy M, Clurman AG, Stein-Thoeringer CK, Markey KA, Docampo MD, Burgos da Silva M, Khan N, Gessner A, Messina JA, Romero K, Lew MV, Bush A, Bohannon L, Brereton DG, Fontana E, Amoretti LA, Wright RJ, Armijo GK, Shono Y, Sanchez-Escamilla M, Castillo Flores N, Alarcon Tomas A, Lin RJ, Yáñez San Segundo L, Shah GL, Cho C, Scordo M, Politikos I, Hayasaka K, Hasegawa Y, Gyurkocza B, Ponce DM, Barker JN, Perales M-A, Giralt SA, Jenq RR, Teshima T, Chao NJ, Holler E, Xavier JB, Pamer EG, van den Brink MRM. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. N Engl J Med. 2020 Feb 27;382(9):822–834.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

February 27, 2020

Volume

382

Issue

9

Start / End Page

822 / 834

Location

United States

Related Subject Headings

  • Transplantation, Homologous
  • Survival Analysis
  • Prospective Studies
  • Prognosis
  • Middle Aged
  • Male
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • General & Internal Medicine
  • Gastrointestinal Microbiome