SUCCESSFUL TREATMENT OF INTESTINAL GRAFT-VERSUS-HOST DISEASE WITH FECAL MICROBIOTA TRANSPLANTATION
Author(s): ,
Yannouck Van Lier
Affiliations:
Hematology,Amsterdam UMC,Amsterdam,Netherlands;Experimental immunology,Amsterdam UMC,Amsterdam,Netherlands;Amsterdam Infection & Immunology institute (AI&II),Amsterdam,Netherlands;Cancer Center Amsterdam (CCA),Amsterdam,Netherlands
,
Mark Davids
Affiliations:
Vascular Medicine,Amsterdam UMC,Amsterdam,Netherlands
,
Nienke Haverkate
Affiliations:
Experimental immunology,Amsterdam UMC,Amsterdam,Netherlands
,
Pieter de Groot
Affiliations:
Vascular Medicine,Amsterdam UMC,Amsterdam,Netherlands
,
Marjolein Donker
Affiliations:
Hematology,Amsterdam UMC,Amsterdam,Netherlands
,
Floor Heubel-Moenen
Affiliations:
Hematology,MUMC+,Maastricht,Netherlands
,
Erfan Nur
Affiliations:
Hematology,Amsterdam UMC,Amsterdam,Netherlands
,
Sacha Zeerleder
Affiliations:
Hematology,Inselspital University Hospital,Bern,Switzerland
,
Max Nieuwdorp
Affiliations:
Vascular Medicine,Amsterdam UMC,Amsterdam,Netherlands
,
Bianca Blom
Affiliations:
Experimental immunology,Amsterdam UMC,Amsterdam,Netherlands
Mette Hazenberg
Affiliations:
Hematology,Amsterdam UMC,Amsterdam,Netherlands
EHA Library. van Lier Y. Jun 15, 2019; 267474; S891
Yannouck van Lier
Yannouck van Lier
Contributions
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Abstract

Abstract: S891

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 16:15 - 16:30

Location: Hall 3A

Background

Disruption of the intestinal microbiome has a negative influence on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT). Decreased gut flora diversity with loss of commensals and pathobiont domination, is associated with an increased risk to develop graft-versus-host disease (GvHD).  Fecal microbiota transplantation (FMT) has successfully been used to treat Clostridium difficile enteritis but the safety and efficacy of FMT in immunocompromised GvHD patients remains to be elucidated.

Aims

  1. To assess the safety and effectiveness of FMT as treatment for GvHD patients in a prospective, single-arm pilot study
  2. To analyze the microbiome dynamics of GvHD patients receiving an FMT

Methods

Fifteen patients with steroid-refractory or steroid-dependent intestinal GvHD received a single FMT from an unrelated, healthy donor via nasoduodenal infusion. Follow-up included collection of blood and fecal samples prior to FMT and at 1, 4, 12 and 24 weeks after FMT as well as clinical follow-up up to 6months.

Results

FMT was well tolerated by all patients, there were no serious adverse events observed that could be attributed to FMT. Response evaluation at 4 weeks after FMT identified 11 participants with a complete response (CR), defined as resolution of all GvHD, without other interventions to alleviate symptoms. In 6 CR patients, the normalization of stool frequency and consistency was sustained throughout the whole period of follow-up, with successful taper of immunosuppressants. Five other responders initially showed improvement of GvHD after FMT but relapsed upon prednisolone taper (CR/sf; complete responders with secondary failure). A durable response to FMT was associated with a better prognosis (Figure 1). Analysis of peripheral blood immune cell subsets did not reveal significant differences. Alpha diversity of fecal samples, analyzed by 16S ribosomal RNA sequencing, was low in patients pre-FMT but improved upon response to treatment in CR and CR/sf patients. One week after FMT, the fecal microbial composition of CR patients resembled that of the donor the most, suggesting a better engraftment of fecal donor species in patients with persistent responses.

 

Conclusion

This pilot study shows the potential of donor FMT to safely restore microbial diversity and improve symptoms of steroid-refractory or steroid-dependent GvHD patients. These encouraging data promote further investigation of this therapy in larger cohorts.

Session topic: 21. Stem cell transplantation - Experimental

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