Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety

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Abstract

Aim. Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD).

Materials and methods. The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR.

Results. After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers of Bifidobacterium spp. (р=0.021), Escherichia coli (р=0.049) and Bacteroides fragilis gr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days, p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group.

Conclusion. FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.

About the authors

O. V. Goloshchapov

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Author for correspondence.
Email: golocht@yandex.ru
ORCID iD: 0000-0002-0736-1269

зав. ОРИТ №3 НИИ ДОГИТ

Russian Federation, Saint-Petersbug

A. B. Chukhlovin

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0001-9703-4378

д.м.н., проф., зав. лаб. трансплантологии НИИ ДОГИТ

Russian Federation, Saint-Petersbug

E. A. Bakin

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0002-5694-4348

к.т.н., ст. науч. сотр. отд. онкологии, гематологии и трансплантологии для подростков и взрослых НИИ ДОГИТ

Russian Federation, Saint-Petersbug

O. V. Stanevich

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0002-6894-6121

мл. науч. сотр. отд. клинической онкологии, врач-инфекционист НИИ ДОГИТ

Russian Federation, Saint-Petersbug

R. V. Klementeva

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0001-5493-4106

врач анестезиолог-реаниматолог ОРИТ №3 НИИ ДОГИТ

Russian Federation, Saint-Petersbug

A. A. Shcherbakov

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0003-4522-4465

врач анестезиолог-реаниматолог ОРИТ №3 НИИ ДОГИТ

Russian Federation, Saint-Petersbug

A. N. Shvetsov

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0001-7173-7673

зав. хирургическим блоком НИИ ДОГИТ

Russian Federation, Saint-Petersbug

M. A. Suvorova

The Explana Research Laboratory

Email: golocht@yandex.ru
ORCID iD: 0000-0002-6292-0385

к.б.н., ген. дир. Научно-исследовательской лаб. ООО «Эксплана»

Russian Federation, Saint-Petersbug

S. N. Bondarenko

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0002-2446-8092

зам. дир. по лечебной работе НИИ ДОГИТ

Russian Federation, Saint-Petersbug

M. A. Kucher

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0001-6114-3214

д.м.н., рук. отд. клинического питания, доц. каф. гематологии, трансфузиологии и трансплантологии фак-та последипломного образования НИИ ДОГИТ

Russian Federation, Saint-Petersbug

A. D. Kulagin

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0002-9589-4136

д.м.н., проф., и.о. дир. НИИ ДОГИТ

Russian Federation, Saint-Petersbug

L. S. Zubarovskaya

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0003-2594-7703

д.м.н., проф., рук. отд. детской онкологии, гематологии и трансплантологии НИИ ДОГИТ

Russian Federation, Saint-Petersbug

I. S. Moiseev

Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University

Email: golocht@yandex.ru
ORCID iD: 0000-0002-4332-0114

д.м.н., зам. дир. НИИ ДОГИТ

Russian Federation, Saint-Petersbug

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