Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study

Abstract

We have previously described clinically relevant reductions in fecal microbiota diversity of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Recipients of high-dose chemotherapy and autologous hematopoietic cell transplantation (auto-HCT) incur similar antibiotic exposures and nutritional alterations. To characterize the fecal microbiota in the auto-HCT population, we analyzed 1,161 fecal samples collected from 534 adult recipients of auto-HCT for lymphoma, myeloma and amyloidosis in an observational study conducted at two transplant centers in the United States. Using 16S ribosomal gene sequencing, we assessed fecal microbiota diversity as measured by the inverse Simpson index, and composition. At both centers, early pre-transplant fecal microbiota diversity was lower than in healthy control subjects and decreased further during the course of transplantation. Loss of diversity and domination by specific bacterial taxa occurred during auto-HCT in patterns similar to allo-HCT. Above-median fecal intestinal diversity in the peri-engraftment period was associated with decreased risk of death or progression (PFS HR 0.46 [95% CI, 0.26-0.82], P=0.008), adjusting for disease and disease status. This suggests that further investigation into the health of the intestinal microbiota in auto-HCT patients and post-transplant outcomes should be undertaken.

The Role of the Gut Microbiome in Pathogenesis, Biology, and Treatment of Plasma Cell Dyscrasias

“…Similar conclusions were drawn from the results of the small pilot study with 15 patients, showing that baseline microbiota were associated with subsequent incidence and severity of nausea, vomiting, neutropenic fever, and rate of neutrophil engraftment (90). Khan et al showed recently that 534 adult recipients of highdose chemotherapy with ASCT had significantly decreased alpha diversity at early pretransplant stages than healthy individuals and that this reduction in diversity tended to be more marked in the course of the procedure (9). The pattern of this loss of diversity and dominance of specific taxa were similar to those seen in patients after alloSCT.…”

“…Recent studies have yielded plenty of information on the differences in microbiota among MM patients and about longitudinal changes acquired during the treatment as well (9). Some recently identified gut microbes are responsible for inducing an inflammatory environment, both within the gut layer and throughout the whole body.…”

Intestinal Microbiome in Hematopoietic Stem Cell Transplantation For Autoimmune Diseases: Considerations and Perspectives on Behalf of Autoimmune Diseases Working Party (ADWP) of the EBMT

“…A large multicenter observational study has confirmed lower mortality rates in patients showing higher diversity of intestinal microbiota at engraftment (3). Recently, microbiota injury has been observed also in recipients of autologous HSCT, who undergo similar antibiotic exposures and nutritional alterations after high-dose chemotherapy and transplant procedure (80). Reduced OS and PFS have been reported in patients with lower peri-engraftment microbiome diversity.…”

The Insider: Impact of the Gut Microbiota on Cancer Immunity and Response to Therapies in Multiple Myeloma

“…Khan and colleagues highlighted interesting similarities in gut microbiota dysbiosis after both autologous- and allogeneic-HSCT in MM patients ( 89 ). Changes in the bacteriome and mycobiome also modulate early toxicity and the rate of neutrophil engraftment after autologous-HSCT ( 90 ).…”