Σάββατο, 1 Απριλίου 2017

MICROBIOTA ROLE IN RESPONSE TO CHEMOTHERAPY

A retrospective study has shown that the presence and abundance of a particular bacterial group in the intestinal microbiota are associated with a significantly lower risk of relapse or disease progression after allogeneic hematopoietic cell transplantation. The findings were reported by Peled et al in the Journal of Clinical Oncology.
Study Details
The study involved assessment of intestinal microbiota of 541 patients with various hematologic malignancies admitted to Memorial Sloan Kettering Cancer Center for allogeneic hematopoietic cell transplantation between 2009 and 2015. The most common malignancies were acute myeloid leukemia (36%), myelodysplastic syndrome (16%), and non-Hodgkin lymphoma (13%).
The microbiota was profiled using 16S ribosomal sequencing of prospectively collected stool samples, with identification of clusters of related operational taxonomic units. Stool samples were collected within 3 weeks after allogeneic hematopoietic cell transplantation.
Association With Relapse/Disease Progression
In a discovery cohort of 271 patients, the candidate clusters of related operational taxonomic unit with the strongest association with disease relapse/progression was that composed mostly of Eubacterium limosum and other related species (hazard ratio [HR] = 0.82, P = .009, per 10-fold increase in abundance). On multivariable analysis adjusting for disease risk index, conditioning intensity, and graft source, presence of this bacterial group was associated with a hazard ratio for relapse/disease progression of 0.84 (P = .01) for every 10-fold increase in abundance in the microbiota. This bacterial group was also associated with a significantly reduced risk of relapse/disease progression in a validation cohort of 271 patients; on multivariable analysis, the hazard ratio was 0.82 (P = .01) for each 10-fold increase in abundance. The second best candidate group from the discovery set had no significant association with outcome in the validation set (HR = 0.96, P = .66). Overall, the bacterial group was present in 422 of the combined cohorts (78%), with a mean abundance of 0.16% and a maximum abundance of 8%.
When patients in the two cohorts were stratified according to presence (any detectable amount) or absence of the bacterial group, those with presence in the microbiota had significantly reduced risk of relapse/disease progression in both the discovery (HR = 0.49, P = .006) and validation cohorts (HR = 0.52, P = .01). In the validation cohort, the 2-year cumulative incidence of relapse/disease progression was 19.8% among those with the bacterial group vs 33.8% in those without the bacterial group. The associations remained significant in both the discovery (HR = 0.46, P = .004) and validation cohorts (HR = 0.54, P = .03) in multivariable analysis adjusting for disease risk index, conditioning intensity, and graft source.
Effect in Subgroups
In subgroup analyses, the association of the bacterial group with a reduced risk for relapse/disease progression was significant for acute myeloid leukemia (HR = 0.56, P = .04) and multiple myeloma (HR = 0.29, P = .004) but not for other disease types. It was also highly significant among patients who received T-cell–replete grafts (HR = 0.40, P < .001), particularly those with unmodified peripheral blood stem cell/bone marrow grafts (HR = 0.40, P = .001). Reduced risk did not achieve statistical significance in recipients of T-cell–depleted grafts (HR = 0.66, P = .12) or cord-blood grafts (HR = 0.38, P = .13).
The investigators concluded: “We found associations between the abundance of a group of bacteria in the intestinal flora and relapse/progression of disease after [allogeneic hematopoietic cell transplantation]. These might serve as potential biomarkers or therapeutic targets to prevent relapse and improve survival after [allogeneic hematopoietic cell transplantation].”
The study was supported by National Institutes of Health awards and training grants; the Lymphoma Foundation; the Susan and Peter Solomon Divisional Genomics Program; Memorial Sloan Kettering Cancer Center Cycle for Survival; and Tow Foundation/Lucille Castori Center for Microbes, Inflammation, and Cancer.
Jonathan U. Peled, MD, PhD, of Memorial Sloan Kettering Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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