168 Fecal Microbiota Transplant in Graft-versus-Host Disease of the Intestines: A Comprehensive Pooled Analysis

Abstract

INTRODUCTION: Graft versus host disease (GVHD) of the intestines is a feared complication after hematopoietic stem cell transplantation (HSCT), and carries high morbidity and mortality. Recently fecal microbiota transplant (FMT) has been explored as a treatment modality for intestinal GVHD. The aim of our study was to pool data from individual feasibility studies to explore the efficacy and safety of FMT for gut GVHD. METHODS: A systematic search was performed for studies in PubMed, Embase, Cochrane database and ClinicalTrials.gov. All studies that reported data on FMT in patients who had previously undergone HSCT were included. Two independent authors conducted the systematic search. Pooled analysis was conducted for safety and efficacy of FMT in HSCT patients. RESULTS: A total of 15 studies comprising a total of 99 patients reported FMT outcomes after HSCT. Indication of FMT was restoration of microbiome in 41, Clostridium difficile infection in 21, and intestinal GVHD in 37 patients. All studies were single center pilot trials. Five studies with 37 patients reported efficacy outcomes for intestinal GVHD. A total of 57 FMTs were performed. All patients had previously failed at least one immunosuppressant regimen. All patients were either steroid resistant or steroid dependent. Overall complete response rate of 62.1% was observed (23 patients). Three additional patients partially responded to FMT. Positive response was accompanied by a decrease in stool volumes and frequency in all patients; reduction in use of anti-motility agents, and cessation of total parenteral nutrition was observed in all responders. All studies reported successful tapering of immunosuppressant and steroid dosage. FMT was generally well tolerated. No treatment-related mortality was reported. Minor adverse events included abdominal pain, nausea, mucosal tears, and minor aspiration without sequelae. Serious adverse events included bleeding in one patient, and grade 3 abdominal pain in one patient (resolved within 24 hours of capsule ingestion). Infections were reported in three patients after FMT (two with bacteremia), but could not be attributed to FMT with certainty. CONCLUSION: FMT is a promising modality for management of intestinal GVHD and carries low morbidity. It appears to be safe and acceptable as a salvage therapy for intestinal GVHD based on the current limited data. The need to withhold antibiotics to allow persistent engraftment may prove challenging in this severely immunocompromised population.