The impact of intestinal microbiota in antithymocyte globulin-based myeloablative allogeneic hematopoietic cell transplantation.

Background: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT) has been reported in platforms with T-cell depletion or postcyclophosphamide-based graft-vs-host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same in platforms of antithymocyte globulin (ATG)-based myeloablative allo-HCT.

Methods: A total of 603 fecal specimens from 100 consecutive patients receiving allo-HCT were collected between December 2018 and July 2020. Fetal samples were profiled with next-generation sequencing of bacterial 16S ribosomal RNA (rRNA) genes.

Results: The diversity decreased to the lowest level at approximately day 12 after allo-HCT and then increased over time. According to the diversity of 314 samples that were collected from 86 patients during the engraftment period, patients were grouped into the low- and high-diversity groups. Two-year overall survival in the high-diversity group was significantly longer than that in the low-diversity group (83.7% vs 60.6%, P = .026). Further analysis revealed that worse outcomes for patients with low diversity were associated with increased risk of worse outcomes for patients with low diversity (adjusted hazard ratio, 4.95; P = .046). Its association with relapse and GVHD was not found. Compositional analysis of fecal microbiota revealed that the abundance of bacteroides decreased greatly during allo-HCT, whereas that of Enterococcus, Klebsiella, and Escherichia was found to be increased.

Conclusions: This study indicates that gut dysbiosis in platforms of ATG-based myeloablative allo-HCT featured loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period was an independent predictor of longer survival.

Lay Summary: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT) is reported in platforms with T-cell depletion or postcyclophosphamide-based graft-vs-host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same pattern in platforms of antithymocyte globulin (ATG)-based T-cell repletion myeloablative allo-HCT. Our study indicated that gut dysbiosis in platforms of ATG-based myeloablative allo-HCT also features loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period is an independent predictor of longer survival.