Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. Academic Article uri icon

Overview

abstract

  • We hypothesized that third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT). In this open-label single-group pilot study, 18 subjects were enrolled before allo-HCT and planned to receive third-party FMT capsules. FMT capsules were administered no later than 4 weeks after neutrophil engraftment, and antibiotics were not allowed within 48 hours before FMT. Five patients did not receive FMT because of the development of early acute gastrointestinal (GI) graft-versus-host disease (GVHD) before FMT (n = 3), persistent HCT-associated GI toxicity (n = 1), or patient decision (n = 1). Thirteen patients received FMT at a median of 27 days (range, 19-45 days) after HCT. Participants were able to swallow and tolerate all FMT capsules, meeting the primary study endpoint of feasibility. FMT was tolerated well, with 1 treatment-related significant adverse event (abdominal pain). Two patients subsequently developed acute GI GVHD, with 1 patient also having concurrent bacteremia. No additional cases of bacteremia occurred. Median follow-up for survivors is 15 months (range, 13-20 months). The Kaplan-Meier estimates for 12-month overall survival and progression-free survival after FMT were 85% (95% confidence interval, 51%-96%) and 85% (95% confidence interval, 51%-96%), respectively. There was 1 nonrelapse death resulting from acute GI GVHD (12-month nonrelapse mortality, 8%; 95% confidence interval, 0%-30%). Analysis of stool composition and urine 3-indoxyl sulfate concentration indicated improvement in intestinal microbiome diversity after FMT that was associated with expansion of stool-donor taxa. These results indicate that empiric third-party FMT after allo-HCT appears to be feasible, safe, and associated with expansion of recipient microbiome diversity. This trial was registered at www.clinicaltrials.gov as #NCT02733744.

authors

  • DeFilipp, Zachariah
  • Peled, Jonathan
  • Li, Shuli
  • Mahabamunuge, Jasmin
  • Dagher, Zeina
  • Slingerland, Ann E
  • Del Rio, Candice
  • Valles, Betsy
  • Kempner, Maria E
  • Smith, Melissa
  • Brown, Jami
  • Dey, Bimalangshu R
  • El-Jawahri, Areej
  • McAfee, Steven L
  • Spitzer, Thomas R
  • Ballen, Karen K
  • Sung, Anthony D
  • Dalton, Tara E
  • Messina, Julia A
  • Dettmer, Katja
  • Liebisch, Gerhard
  • Oefner, Peter
  • Taur, Ying
  • Pamer, Eric G
  • Holler, Ernst
  • Mansour, Michael K
  • van den Brink, Marcel R M
  • Hohmann, Elizabeth
  • Jenq, Robert R
  • Chen, Yi-Bin

publication date

  • April 10, 2018

Research

keywords

  • Fecal Microbiota Transplantation
  • Hematopoietic Stem Cell Transplantation

Identity

PubMed Central ID

  • PMC5894265

Scopus Document Identifier

  • 85048688282

Digital Object Identifier (DOI)

  • 10.1182/bloodadvances.2018017731

PubMed ID

  • 29592876

Additional Document Info

volume

  • 2

issue

  • 7