Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients.

Autor: van Lier YF; Department of Hematology, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity (AII), Cancer Center Amsterdam, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands., Davids M; Department of Vascular Medicine, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands., Haverkate NJE; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity (AII), Cancer Center Amsterdam, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands., de Groot PF; Department of Vascular Medicine, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands., Donker ML; Department of Hematology, Amsterdam UMC, location VUMC, 1081 HV Amsterdam, Netherlands., Meijer E; Department of Hematology, Amsterdam UMC, location VUMC, 1081 HV Amsterdam, Netherlands., Heubel-Moenen FCJI; Department of Hematology, Maastricht University Medical Center, 6229 HX Maastricht, Netherlands., Nur E; Department of Hematology, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands., Zeerleder SS; Department of Hematology, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands.; Department of Immunopathology, Sanquin Research, 1066 CX Amsterdam, Netherlands.; Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.; Department for BioMedical Research, University of Bern, 3010 Bern, Switzerland., Nieuwdorp M; Department of Vascular Medicine, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands.; Diabetes Center, Department of Internal Medicine, Amsterdam UMC, location VUMC, 1081 HV Amsterdam, Netherlands.; Institute for Cardiovascular Research (ICaR), Amsterdam UMC, location VUMC, 1081 HV Amsterdam, Netherlands.; Wallenberg Laboratory, University of Gothenburg, SE-413 45 Goteborg, Sweden., Blom B; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity (AII), Cancer Center Amsterdam, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands., Hazenberg MD; Department of Hematology, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands. m.d.hazenberg@amsterdamumc.nl.; Department of Experimental Immunology, Amsterdam Institute for Infection and Immunity (AII), Cancer Center Amsterdam, Amsterdam UMC, location AMC, 1105 AZ Amsterdam, Netherlands.; Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, Netherlands.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2020 Aug 12; Vol. 12 (556).
DOI: 10.1126/scitranslmed.aaz8926
Abstrakt: Disruption of the intestinal microbiota occurs frequently in allogeneic hematopoietic cell transplantation (allo-HCT) recipients and predisposes them to development of graft-versus-host disease (GvHD). In a prospective, single-center, single-arm study, we investigated the effect of donor fecal microbiota transplantation (FMT) on symptoms of steroid-refractory or steroid-dependent, acute or late-onset acute intestinal GvHD in 15 individuals who had undergone allo-HCT. Study participants received a fecal suspension from an unrelated healthy donor via nasoduodenal infusion. Donor FMT was well tolerated, and infection-related adverse events did not seem to be related to the FMT procedure. In 10 of 15 study participants, a complete clinical response was observed within 1 month after FMT, without additional interventions to alleviate GvHD symptoms. This response was accompanied by an increase in gut microbial α-diversity, a partial engraftment of donor bacterial species, and increased abundance of butyrate-producing bacteria, including Clostridiales and Blautia species. In 6 of the 10 responding donor FMT recipients, immunosuppressant drug therapy was successfully tapered. Durable remission of steroid-refractory or steroid-dependent GvHD after donor FMT was associated with improved survival at 24 weeks after donor FMT. This study highlights the potential of donor FMT as a treatment for steroid-refractory or steroid-dependent GvHD, but larger clinical trials are needed to confirm the safety and efficacy of this procedure.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE