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Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity

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

Key Points

  • The administration of third-party FMT capsules early after allogeneic HCT is feasible and appears safe.

  • FMT is associated with early expansion of microbiome diversity in transplant recipients.

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.

  • Submitted February 20, 2018.
  • Accepted February 27, 2018.
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