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Fecal microbiota transplantation to prevent acute GVHD after allogeneic stem cell transplantation

Dr. Rashidi

Armin Rashidi


Fred Hutchinson Cancer Center

Project Term: July 1, 2023 - September 30, 2026

In up to half of patients with hematologic malignancies undergoing allogeneic stem cell transplantation, the trajectory of a smooth recovery toward cure is disrupted by acute graft-versus-host disease (aGVHD). Inspired by the role of intestinal microbial communities in aGVHD pathogenesis, we recently completed the largest fecal microbiota transplantation (FMT) trial to date in transplant recipients. We established the safety of standardized third-party FMT and characterized FMT effects on the microbiota, leading to the proposed randomized, placebo-controlled phase 2 trial of FMT to prevent aGVHD.

Lay Abstract

Allogeneic stem cell transplantation is the only curative treatment option for many patients with blood cancer. Unfortunately, this approach carries a high morbidity and mortality risk. Up to half of transplant recipients develop acute graft-versus-host disease (aGVHD) within 6 months after transplant. aGVHD occurs when donor cells attack the healthy tissues of the host, worsening the quality of life and sometimes leading to death. Affected patients suffer from skin rash, nausea, vomiting, diarrhea, and liver damage. Thus, effective prevention of aGVHD is a major goal in transplantation. Recent studies have shown that patients experiencing more disruptions to their gut microbial communities shortly after transplant are at higher risk for aGVHD. These disruptions are caused by antibiotic exposures and nutritional changes during and after transplant. We recently conducted a trial where we transferred microbes from stool samples obtained from healthy donors to transplant patients with the goal of repairing the injury caused to the gut microbes. This has been the largest trial to date of its kind with 74 transplant recipients. We established the safety of fecal microbiota transplantation (FMT) in these patients and characterized the effect of FMT on the gut microbiota. Here we propose the subsequent trial where we aim to prevent aGVHD by FMT. We will randomize 194 transplant recipients to receive FMT or placebo, each consisting of 3 oral capsules daily for 10 consecutive days early after transplant. Both patients and physicians will be blinded to the treatment arm. The primary objective of the trial is to decrease the incidence of acute GVHD by 20% in the FMT arm compared to placebo. Patients will be followed for 6 months after transplant. Over the last several years, our research has focused on gut microbial changes in immunocompromised patients with blood cancer and how these changes impact outcomes and complications of curative-intent therapy. Using our unique prior data and multidisciplinary expertise in performing FMT in such patients, and with ~500 allogeneic transplants per year at our center, we are confident the proposed trial will be successfully conducted. The desired outcome of this effort will be an innovative supportive care that allows patients to undergo curative transplants with fewer complications, a better quality of life, and prolonged survival.

Academic Clinical Trials Program (ACT)
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