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24-03-2017 | Oncology | News | Article

Intestinal microbiota linked to reduced risk for post-HSCT relapse

medwireNews: Researchers have found an association between increased abundance of a bacterial group primarily comprising Eubacterium limosum in the intestinal microbiota and a reduced risk for relapse after undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

They explain that other outcomes – such as graft-versus-host disease (GVHD) and overall survival – have been linked with alterations in gut flora, and add: “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 [allogeneic HSCT].”

The study included 541 patients with available stool samples collected during the initial 21 days after undergoing allogeneic HSCT for various primary hematologic malignancies at a US center between 2009 and 2015.

The team used 16S ribosomal sequencing to analyze the bacterial composition of the samples, and theorizing that “evolutionarily related species exhibit functional similarities,” generated phylogenetic groups termed “clusters of related operational taxonomic units (crOTU).”

One such group, crOTU 1614 – mainly (67%) composed of E. limosum sequences – was significantly associated with a reduced risk for relapse or disease progression in both the discovery (n=271) and validation (n=270) cohorts after adjusting for conditioning intensity, graft source, and disease risk index. The corresponding hazard ratios (HRs) for relapse were 0.84 and 0.82 for every 10-fold increase in abundance of the crOTU.

The association remained when crOTU 1614 was considered as a binary variable, such that presence (defined as any detectable amount) versus absence of the bacterial group significantly correlated with a reduced relapse risk in the discovery and validation cohorts, with adjusted HRs of 0.46 and 0.54, respectively.

Over 2 years, relapse occurred in 19.8% of patients with stool samples that were positive for crOTU 1614, compared with 33.8% of those negative for the bacterial group, report Jonathan Peled (Memorial Sloan Kettering Cancer Center, New York, USA) and team in the Journal of Clinical Oncology.

Subgroup analysis showed that the association between crOTU 1614 and reduced relapse risk was limited to recipients of T-cell–replete grafts (HR=0.40). And even in this subgroup, the association was only significant for patients given unmodified peripheral blood stem cell/bone marrow grafts (HR=0.40), not those who received cord-blood grafts.

In a related editorial, Joseph Antin (Dana-Farber Cancer Institute/Brigham and Women’s Hospital, Boston, Massachusetts, USA) comments that “[t]he fact that the reduced risk of relapse is more noticeable in patients with T-cell–replete transplantations does suggest an interaction between the bacteria and the immune system that is lost when T cells are depleted from the graft.”

He says that many questions remain unanswered – such as, the dynamics of the interaction between crOTU 1614 and the generation of graft-versus-leukemia responses and with the bacteria-derived immunosuppressive drugs tacrolimus and sirolimus.

Nonetheless, Antin compliments the researchers “on their identification of this important area in transplantation biology,” adding that one “can assume that their systematic approach to evaluation of the intestinal microflora in the context of acute GVHD, chronic GVHD, conditioning regimen, stem-cell source, and diagnosis will result not only in improvements in transplantation-related outcomes but also in fundamental insights about the interactions between the immune system and the bacterial world that surrounds us.”

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group

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