期刊
JOURNAL OF CLINICAL ONCOLOGY
卷 35, 期 15, 页码 1650-+出版社
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.2016.70.3348
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资金
- National Institutes of Health (NIH) [R01-HL069929, R01-AI100288, R01-AI080455, R01-AI101406, 5KL2-TR001115-03, P01-CA023766, R01-HL124112, P30CA008748]
- NIH [2T32CA009207-36A1, UL1TR00457]
- Lymphoma Foundation
- Susan and Peter Solomon Divisional Genomics Program
- MSKCC Cycle for Survival
- Tow Foundation/Lucille Castori Center for Microbes, Inflammation, and Cancer
- Merck/Society for Immunotherapy of Cancer Clinical Fellowship Award
- Young Investigator Award of the Conquer Cancer Foundation
- MSKCC Clinical Scholars Biomedical Research Training Program Award of the Charles A. Dana Foundation
PurposeThe 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.MethodsThe 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.ResultsHigher 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.ConclusionWe 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.
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