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

Authors: DeFilipp, Z.; Peled, J. U.; Li, S.; Mahabamunuge, J.; Dagher, Z.; Slingerland, A. E.; Del Rio, C.; Valles, B.; Kempner, M. E.; Smith, M.; Brown, J.; Dey, B. R.; El-Jawahri, A.; McAfee, S. L.; Spitzer, T. R.; Ballen, K. K.; Sung, A. D.; Dalton, T. E.; Messina, J. A.; Dettmer, K.; Liebisch, G.; Oefner, P.; Taur, Y.; Pamer, E. G.; Holler, E.; Mansour, M. K.; van den Brink, M. R. M.; Hohmann, E.; Jenq, R. R.; Chen, Y. B.
Article Title: Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity
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.
Keywords: transplantation; risk; versus-host-disease; stem-cell; clostridium-difficile infection; gut; intestinal microbiota
Journal Title: Blood Advances
Volume: 2
Issue: 7
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2018-04-10
Start Page: 745
End Page: 753
Language: English
ACCESSION: WOS:000430751400002
DOI: 10.1182/bloodadvances.2018017731
PMCID: PMC5894265
PUBMED: 29592876
Notes: Article -- Source: Wos
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MSK Authors
  1. Eric Pamer
    242 Pamer
  2. Ying Taur
    85 Taur
  3. Jonathan U Peled
    40 Peled