Dataset Information

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

ABSTRACT: 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.).

SUBMITTER: Peled JU

PROVIDER: S-EPMC7534690 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Peled Jonathan U JU Gomes Antonio L C ALC Devlin Sean M SM Littmann Eric R ER Taur Ying Y Sung Anthony D AD Weber Daniela D Hashimoto Daigo D Slingerland Ann E AE Slingerland John B JB Maloy Molly M Clurman Annelie G AG Stein-Thoeringer Christoph K CK Markey Kate A KA Docampo Melissa D MD Burgos da Silva Marina M Khan Niloufer N Gessner André A Messina Julia A JA Romero Kristi K Lew Meagan V MV Bush Amy A Bohannon Lauren L Brereton Daniel G DG Fontana Emily E Amoretti Luigi A LA Wright Roberta J RJ Armijo Gabriel K GK Shono Yusuke Y Sanchez-Escamilla Míriam M Castillo Flores Nerea N Alarcon Tomas Ana A Lin Richard J RJ Yáñez San Segundo Lucrecia L Shah Gunjan L GL Cho Christina C Scordo Michael M Politikos Ioannis I Hayasaka Kasumi K Hasegawa Yuta Y Gyurkocza Boglarka B Ponce Doris M DM Barker Juliet N JN Perales Miguel-Angel MA Giralt Sergio A SA Jenq Robert R RR Teshima Takanori T Chao Nelson J NJ Holler Ernst E Xavier Joao B JB Pamer Eric G EG van den Brink Marcel R M MRM

The New England journal of medicine 20200201 9

<h4>Background</h4>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.<h4>Methods</h4>The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hemat ...[more]

PMID: 32101664

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Project description:Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown.To investigate whether changes in gut microbiota are associated with PCs after HCT.A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis.One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30-4.00; P?=?0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32-3.98; P?=?0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22-5.32; P?=?0.015), and ?-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10-5.65; P?=?0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42-31.80; P?=?0.016), whereas ?-proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49-8.21; P?=?0.006) and overall mortality (HR, 3.52; 95% CI, 1.28-9.21; P?=?0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25-5.22; P?=?0.009).This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and ?-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted.

Dataset Information

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

Publications

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

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