S891 SUCCESSFUL TREATMENT OF INTESTINAL GRAFT‐VERSUS‐HOST DISEASE WITH FECAL MICROBIOTA TRANSPLANTATION

Abstract

Background:Disruption of the intestinal microbiome has a negative influence on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT). Decreased gut flora diversity with loss of commensals and pathobiont domination, is associated with an increased risk to develop graft‐versus‐host disease (GvHD). Fecal microbiota transplantation (FMT) has successfully been used to treat Clostridium difficile enteritis but the safety and efficacy of FMT in immunocompromised GvHD patients remains to be elucidated.Aims:1. To assess the safety and effectiveness of FMT as treatment for GvHD patients in a prospective, single‐arm pilot study2. To analyze the microbiome dynamics of GvHD patients receiving an FMTMethods:Fifteen patients with steroid‐refractory or steroid‐dependent intestinal GvHD received a single FMT from an unrelated, healthy donor via nasoduodenal infusion. Follow‐up included collection of blood and fecal samples prior to FMT and at 1, 4, 12 and 24 weeks after FMT as well as clinical follow‐up up to 6months.Results:FMT was well tolerated by all patients, there were no serious adverse events observed that could be attributed to FMT. Response evaluation at 4 weeks after FMT identified 11 participants with a complete response (CR), defined as resolution of all GvHD, without other interventions to alleviate symptoms. In 6 CR patients, the normalization of stool frequency and consistency was sustained throughout the whole period of follow‐up, with successful taper of immunosuppressants. Five other responders initially showed improvement of GvHD after FMT but relapsed upon prednisolone taper (CR/sf; complete responders with secondary failure). A durable response to FMT was associated with a better prognosis (Figure 1). Analysis of peripheral blood immune cell subsets did not reveal significant differences. Alpha diversity of fecal samples, analyzed by 16S ribosomal RNA sequencing, was low in patients pre‐FMT but improved upon response to treatment in CR and CR/sf patients. One week after FMT, the fecal microbial composition of CR patients resembled that of the donor the most, suggesting a better engraftment of fecal donor species in patients with persistent responses.Summary/Conclusion:This pilot study shows the potential of donor FMT to safely restore microbial diversity and improve symptoms of steroid‐refractory or steroid‐dependent GvHD patients. These encouraging data promote further investigation of this therapy in larger cohorts.image