Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation

Peled, Jonathan U.

; Devlin, Sean M. ; Staffas, Anna ; Lumish, Melissa ; Khanin, Raya ; Littmann, Eric R. ; Ling, Lilan ; Kosuri, Satyajit ; Maloy, Molly ; Slingerland, John B. ; Ahr, Katya F. ; Porosnicu Rodriguez, Kori A. ; Shono, Yusuke ; Slingerland, Ann E. ; Docampo, Melissa D. ; Sung, Anthony D. ; Weber, Daniela ; Alousi, Amin M. ; Gyurkocza, Boglarka ; Ponce, Doris M. ; Barker, Juliet N. ; Perales, Miguel-Angel ; Giralt, Sergio A. ; Taur, Ying ; Pamer, Eric G. ; Jenq, Robert R. ; van den Brink, Marcel R. M.

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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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