Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach to prevent acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplantation (alloHCT), according to findings from recent clinical trials. Researchers from the Fred Hutchinson Cancer Center and the University of Washington have been investigating the role of gut microbiota restoration to reduce the risk of severe aGVHD, which affects nearly half of the patients receiving alloHCT, even with standard prophylaxis.
Acute graft-versus-host disease occurs when the transplanted immune cells from the graft attack the recipient’s tissues, particularly targeting organs like the gut, skin, and liver. A disruption of the gut microbiota during the early post-transplant phase appears to increase the incidence and severity of subsequent cases of aGVHD. Various studies have demonstrated how microbial composition plays a pivotal role, influencing immune responses and disease outcomes.
Given these findings, the clinical team devised a randomized, double-blind placebo-controlled trial aiming to determine whether fecal microbiota transplantation from healthy donors early after transplantation could mitigate the occurrence of severe cases of aGVHD. The trial's initial run-in phase involved 20 patients receiving FMT from three different donors.
Results from this run-in phase indicated promises of FMT as it was found to be safe and capable of restoring microbial diversity and increasing the proportions of beneficial gut bacteria. Notably, the engraftment rate—the success at which the transplanted microbiota establishes itself within the patient—was found to differ among the donors. Donor 3 showed the most significant engraftment rate at 66%, outpacing donors one and two.
The researchers observed clinical outcomes and microbiota composition shifts, marking notable changes consistent with successful engraftment. The alignment between microbiota profiles of donor 3 and patient post-FMT samples indicated this donor’s product could be superior for potential clinical benefits. "Our findings suggest...a clinically relevant donor effect and demonstrate feasibility of evidence-based donor selection," noted the researchers.
Throughout the study, all patients were closely monitored for adverse events with no significant complications directly related to FMT treatments recorded. Minor gastrointestinal symptoms were observed, but no grade 3 or higher treatment-related events occurred.
With no patients being lost to follow-up within six months, the study underscored the importance of choosing the optimal donor, particularly how distinct microbiota profiles may correlate with patient outcomes. Especially concerning was the observation of severe grade III-IV aGVHD occurring only among patients treated with FMT from donor 1, highlighting the necessity of selection based on donor microbiota composition.
The trial is now entering its randomized phase with the best donor, donor 3, designated for future patients. The prospective randomized phase aims to establish whether FMT not just restores microbiota but actively reduces the risk of severe complications linked with graft-versus-host disease, moving beyond the preliminary encouraging insights.
Overall, the approach of utilizing FMT presents not only another means of restoring gut health but also showcases precision medicine's role within transplantation contexts. The findings may pave the way for future interventions aimed at enhancing recovery outcomes for alloHCT recipients facing the risk of severe complications.