Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
27 02 2020
27 02 2020
Historique:
entrez:
27
2
2020
pubmed:
27
2
2020
medline:
17
3
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.).
Sections du résumé
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.).
Identifiants
pubmed: 32101664
doi: 10.1056/NEJMoa1900623
pmc: PMC7534690
mid: NIHMS1631841
doi:
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
822-834Subventions
Organisme : NCI NIH HHS
ID : 1R01CA228308-01
Pays : United States
Organisme : NIA NIH HHS
ID : P01-AG052359 (Project 2)
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA023766
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228308
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : R01 AI137269-01
Pays : International
Organisme : NHLBI NIH HHS
ID : K08HL143189-01A1
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002553
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG028716
Pays : United States
Organisme : NCI NIH HHS
ID : P01-CA023766 (Project 4)
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001115-03
Pays : United States
Organisme : Japan Society for the Promotion of Science
ID : 17K09945
Pays : International
Organisme : Japan Society for the Promotion of Science
ID : 17H04206
Pays : International
Organisme : United States
ID : 2016-013
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL124112
Pays : United States
Organisme : NHLBI NIH HHS
ID : 1R01HL124112-01A
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI032135
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI124275
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA203950-01
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095706
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001115
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01-HL125571
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014236
Pays : United States
Organisme : NCI NIH HHS
ID : R01-HL125571
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI100288
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI100851
Pays : United States
Organisme : NCI NIH HHS
ID : U01 AI124275
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL143189
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA203950
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01-HL123340
Pays : United States
Organisme : NIA NIH HHS
ID : 2P30AG028716-11
Pays : United States
Organisme : NIH HHS
ID : R01 AI032135
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137269
Pays : United States
Organisme : NCI NIH HHS
ID : 1R01CA228358-01
Pays : United States
Organisme : National Institute of Allergy and Infectious Diseases
ID : AI095706
Pays : International
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 Massachusetts Medical Society.
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