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J Clin Oncol. 2017 May 20;35(15):1650-1659. doi: 10.1200/JCO.2016.70.3348. Epub 2017 Mar 15.

Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation.

Author information

1
Jonathan U. Peled, Sean M. Devlin, Anna Staffas, Melissa Lumish, Raya Khanin, Eric R. Littmann, Lilan Ling, Satyajit Kosuri, Molly Maloy, John B. Slingerland, Katya F. Ahr, Kori A. Porosnicu Rodriguez, Yusuke Shono, Ann E. Slingerland, Melissa D. Docampo, Boglarka Gyurkocza, Doris M. Ponce, Juliet N. Barker, Miguel-Angel Perales, Sergio A. Giralt, Ying Taur, Eric G. Pamer, Robert R. Jenq, and Marcel R.M. van den Brink, Memorial Sloan Kettering Cancer Center; Jonathan U. Peled, Melissa D. Docampo, Boglarka Gyurkocza, Doris M. Ponce, Juliet N. Barker, Miguel-Angel Perales, Sergio A. Giralt, Ying Taur, Eric G. Pamer, Robert R. Jenq, and Marcel R.M. van den Brink, Weill Cornell Medical College; Melissa Lumish, New York University Langone Medical Center, New York, NY; Anthony D. Sung, Duke University Medical Center, Durham, NC; Daniela Weber, University Medical Center, Regensburg, Germany; and Amin M. Alousi, University of Texas MD Anderson Cancer Center, Houston, TX.

Abstract

Purpose The major causes of mortality after allogeneic hematopoietic-cell transplantation (allo-HCT) are relapse, graft-versus-host disease (GVHD), and infection. We have reported previously that alterations in the intestinal flora are associated with GVHD, bacteremia, and reduced overall survival after allo-HCT. Because intestinal bacteria are potent modulators of systemic immune responses, including antitumor effects, we hypothesized that components of the intestinal flora could be associated with relapse after allo-HCT. Methods The intestinal microbiota of 541 patients admitted for allo-HCT was profiled by means of 16S ribosomal sequencing of prospectively collected stool samples. We examined the relationship between abundance of microbiota species or groups of related species and relapse/progression of disease during 2 years of follow-up time after allo-HCT by using cause-specific proportional hazards in a retrospective discovery-validation cohort study. Results Higher abundance of a bacterial group composed mostly of Eubacterium limosum in the validation set was associated with a decreased risk of relapse/progression of disease (hazard ratio [HR], 0.82 per 10-fold increase in abundance; 95% CI, 0.71 to 0.95; P = .009). When the patients were categorized according to presence or absence of this bacterial group, presence also was associated with less relapse/progression of disease (HR, 0.52; 95% CI, 0.31 to 0.87; P = .01). The 2-year cumulative incidences of relapse/progression among patients with and without this group of bacteria were 19.8% and 33.8%, respectively. These associations remained significant in multivariable models and were strongest among recipients of T-cell-replete allografts. Conclusion We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after allo-HCT. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after allo-HCT.

PMID:
28296584
PMCID:
PMC5455763
DOI:
10.1200/JCO.2016.70.3348
[Indexed for MEDLINE]
Free PMC Article

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