Third-Party Fecal Microbiota Transplantation for High-Risk Treatment-Naïve Acute GVHD of the Lower Gi Tract

Authors

Zachariah DeFilipp
Ashish V Damania
Haesook T Kim
Chia-Chi Chang
Areej El-Jawahri
Steven L McAfee
Aj S Bottoms
Vesselina Toncheva
Melissa M Smith
Maria Dolaher
Lindsey Perry
Meghan White
Brittany Diana
Sheila Connolly
Bimalangshu R Dey
Matthew J Frigault
Richard A Newcomb
Paul V O'Donnell
Thomas R Spitzer
Michael K Mansour
Daniela Weber
Nadim J Ajami
Elizabeth Hohmann
Robert R Jenq
Yi-Bin Chen

Publication Date

5-14-2024

Journal

Blood Advances

Abstract

Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% of participants able to swallow ≥40 of the 75 scheduled capsules. Ten participants (9 treatment-naïve; 1 steroid-refractory) were enrolled and treated. The study met the primary end point, with 9 of 10 participants completing all eligible doses. Organ-specific LGI complete response rate at day 28 was 70%. Initial clinical response was observed within 1 week for all responders, and clinical responses were durable without recurrent LGI GVHD in complete responders. Exploratory analyses suggest that alpha diversity increased after FMT. Although recipient microbiome composition never achieved a high degree of donor similarity, expansion of donor-derived species and increases in tryptophan metabolites and short-chain fatty acids were observed within the first 7 days after FMT. Investigation into the use of microbiome-targeted interventions earlier in the treatment paradigm for acute LGI GVHD is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT04139577.

Keywords

Humans, Graft vs Host Disease, Fecal Microbiota Transplantation, Male, Female, Middle Aged, Adult, Gastrointestinal Microbiome, Aged, Pilot Projects, Acute Disease, Treatment Outcome

Comments

Supplementary Materials

PMID: 38471063