TY - JOUR
T1 - Intestinal microbiota and Relapse after hematopoietic-Cell transplantation
AU - Peled, Jonathan U.
AU - Devlin, Sean M.
AU - Staffas, Anna
AU - Lumish, Melissa
AU - Khanin, Raya
AU - Littmann, Eric R.
AU - Ling, Lilan
AU - Kosuri, Satyajit
AU - Maloy, Molly
AU - Slingerland, John B.
AU - Ahr, Katya F.
AU - Porosnicu Rodriguez, Kori A.
AU - Shono, Yusuke
AU - Docampo, Melissa D.
AU - Gyurkocza, Boglarka
AU - Ponce, Doris M.
AU - Barker, Juliet N.
AU - Perales, Miguel Angel
AU - Giralt, Sergio A.
AU - Taur, Ying
AU - Pamer, Eric G.
AU - Jenq, Robert R.
AU - Van Den Brink, Marcel R.M.
N1 - Publisher Copyright:
© 2017 by American Society of Clinical Oncology. All rights reserved.
PY - 2017/5/20
Y1 - 2017/5/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2016.70.3348
DO - 10.1200/JCO.2016.70.3348
M3 - Article
C2 - 28296584
AN - SCOPUS:85021854564
SN - 0732-183X
VL - 35
SP - 1650
EP - 1659
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15
ER -