Fecal Microbiota Transplantation As a Therapeutic Option for Graft-Versus-Host-Disease: A Systematic Review and Future Directions

Introduction:

In recent years, there has been an expanding focus on interplay between intestinal microbiotal diversity and outcome of acute graft versus host disease(GVHD) in hematopoietic stem cell transplantation (HCT) recipients. One of the compelling intervention to maintain healthy gut microbiota for better outcome of GVHD in HCT recipients is Fecal microbial transplantation(FMT). Several non randomized small clinical studies and case reports on the efficacy and safety of FMT were reported so far. However, the ultimate role of FMT as a therapeutic option to treat GVHD is yet to be determined due to lack of randomised, large scale, statistically significant studies. Here in, we report a systemic review of literature available so far in an effort to establish a definite role of FMT.

Methodology: A systemic literature search was conducted using various electronic databases. The case reports, case series and clinical studies related to FMT were used as a therapeutic or preventative modality specifically for GVHD are included.

Results: Upon pooling of data, 87 patients from 6 studies and 5 case reports were included in the study in which complete remission(CR) occured in 43.7% and partial remission(PR) occured in 20.7% patients which is equivalent to 64.4% overall response rate in treating GVHD. Furthermore, out of all the species in fecal matter, clostridium was found to be the most valuable species in decreasing the rates of GVHD re-occurrence. Only a limited number of patients had treatment-related mortality

(TRM) from GVHD while few showed mild GI-related (abdominal pain/distention, nausea, regurgitation) and non-GI adverse reactions including infections, anemia, thrombocytopenia, paroxysmal, and atrial fibrillation. We emphasize that the most of the patients did not have any major complications after FMT.

Conclusion:

We conclude that the FMT is a safe and effective strategy for the management of GVHD based on our study. The establishment of gut diversity along with the patient's intrinsic factors like fucosyltransferase 2 (FUT2) secretor status and baseline gut microbial diversity play a major role in the success of FMT. Given the restricted size and absence of randomized data, one cannot portray FMT as a standard of care yet, however, the low or absent toxicity along with improvement in survival justifies this modality to be tested in a randomized fashion. We strongly encourage the transplant community to enroll patients in innovative trials utilizing FMT, as this may be a one of the safest strategies for both prevention and treatment of GVHD