• Jonathan U Peled, Antonio L C Gomes, Sean M Devlin, Eric R Littmann, Ying Taur, Anthony D Sung, Daniela Weber, Daigo Hashimoto, Ann E Slingerland, John B Slingerland, Molly Maloy, Annelie G Clurman, Christoph K Stein-Thoeringer, Kate A Markey, Melissa D Docampo, Marina Burgos da Silva, Niloufer Khan, André Gessner, Julia A Messina, Kristi Romero, Meagan V Lew, Amy Bush, Lauren Bohannon, Daniel G Brereton, Emily Fontana, Luigi A Amoretti, Roberta J Wright, Gabriel K Armijo, Yusuke Shono, Míriam Sanchez-Escamilla, Nerea Castillo Flores, Ana Alarcon Tomas, Richard J Lin, Lucrecia Yáñez San Segundo, Gunjan L Shah, Christina Cho, Michael Scordo, Ioannis Politikos, Kasumi Hayasaka, Yuta Hasegawa, Boglarka Gyurkocza, Doris M Ponce, Juliet N Barker, Miguel-Angel Perales, Sergio A Giralt, Robert R Jenq, Takanori Teshima, Nelson J Chao, Ernst Holler, Joao B Xavier, Eric G Pamer, and van den BrinkMarcel R MMRMFrom the Adult Bone Marrow Transplantation Service (J.U.P., M.M., A.G.C., K.A.M., N.K., D.G.B., M.S.-E., N.C.F., A.A.T., R.J.L., L.Y.S.S., G.L.S., C.C., M.S., I.P., B.G., D.M.P., J.N.B., M.-A.P., S.A.G., M.R.M.B.) and the Infecti.
• From the Adult Bone Marrow Transplantation Service (J.U.P., M.M., A.G.C., K.A.M., N.K., D.G.B., M.S.-E., N.C.F., A.A.T., R.J.L., L.Y.S.S., G.L.S., C.C., M.S., I.P., B.G., D.M.P., J.N.B., M.-A.P., S.A.G., M.R.M.B.) and the Infectious Disease Service (Y.T., E.F., L.A.A., R.J.W., E.G.P.), Department of Medicine, the Department of Epidemiology and Biostatistics (S.M.D.), the Department of Immunology, Sloan Kettering Institute (A.L.C.G., E.R.L., A.E.S., J.B.S., C.K.S.-T., M.D.D., M.B.S., G.K.A., Y.S., M.R.M.B.), and the Program for Computational and Systems Biology (J.B.X.), Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Weill Cornell Medical College (J.U.P., Y.T., K.A.M., M.D.D., R.J.L., G.L.S., C.C., M.S., I.P., B.G., D.M.P., J.N.B., M.-A.P., S.A.G., M.R.M.B.) - both in New York; Duchossois Family Institute of the University of Chicago, Chicago (E.R.L., E.G.P.); the Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University Medical Center (A.D.S., M.V.L., A.B., L.B., N.J.C.), the Division of Infectious Diseases, Department of Medicine, Duke University (J.A.M.), and the Duke Office of Clinical Research, Duke University School of Medicine (K.R.) - all in Durham, NC; the Department of Hematology and Oncology, Internal Medicine III, University Medical Center (D.W., E.H.), the Collaborative Research Center Transregio 221 (D.W., A.G., E.H.), and Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg (A.G.) - all in Regensburg, Germany; the Department of Hematology, Hokkaido University Faculty of Medicine (D.H., Y.H., T.T.), and the Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital (K.H., T.T.) - both in Sapporo, Japan; Research Institute Marqués de Valdecilla-IDIVAL (M.S.-E.) and the Department of Hematology, Hospital Universitario Marqués de Valdecilla-IDIVAL, University of Cantabria (L.Y.S.S.), Santander, and Hospital Universitario Puerta de Hierro, Madrid (A.A.T.) - all in Spain; and the Departments of Genomic Medicine and Stem Cell Transplantation Cellular Therapy, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston (R.R.J.).
• N. Engl. J. Med. 2020 Feb 27; 382 (9): 822834822-834.

BackgroundRelationships 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.MethodsThe 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.ResultsWe 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.ConclusionsPatterns 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.).Copyright © 2020 Massachusetts Medical Society.

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