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FMT fires up treatment of GvHD
Allogeneic hematopoietic cell transplantation (HCT) is a beneficial treatment for hematological malignancies. However, HCT can lead to graft-versus-host disease (GvHD), which affects various organs including the gut. Fecal microbial transplantation (FMT) from allogeneic donors has successfully treated intestinal disorders such as Clostridium difficile infection and ulcerative colitis. van Lier et al. conducted a single-arm clinical trial to investigate whether allogeneic FMT could ameliorate symptoms of intestinal GvHD in 15 HCT recipients. Within a month of treatment, intestinal GvHD resolved and gut microbial diversity was restored in 10 of 15 study participants. Although confirmation is required in larger trials, allogeneic FMT may be a promising treatment for intestinal GvHD.
Abstract
Disruption of the intestinal microbiota occurs frequently in allogeneic hematopoietic cell transplantation (allo-HCT) recipients and predisposes them to development of graft-versus-host disease (GvHD). In a prospective, single-center, single-arm study, we investigated the effect of donor fecal microbiota transplantation (FMT) on symptoms of steroid-refractory or steroid-dependent, acute or late-onset acute intestinal GvHD in 15 individuals who had undergone allo-HCT. Study participants received a fecal suspension from an unrelated healthy donor via nasoduodenal infusion. Donor FMT was well tolerated, and infection-related adverse events did not seem to be related to the FMT procedure. In 10 of 15 study participants, a complete clinical response was observed within 1 month after FMT, without additional interventions to alleviate GvHD symptoms. This response was accompanied by an increase in gut microbial α-diversity, a partial engraftment of donor bacterial species, and increased abundance of butyrate-producing bacteria, including Clostridiales and Blautia species. In 6 of the 10 responding donor FMT recipients, immunosuppressant drug therapy was successfully tapered. Durable remission of steroid-refractory or steroid-dependent GvHD after donor FMT was associated with improved survival at 24 weeks after donor FMT. This study highlights the potential of donor FMT as a treatment for steroid-refractory or steroid-dependent GvHD, but larger clinical trials are needed to confirm the safety and efficacy of this procedure.
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