FARAH study Fecal trAnsplantation to Reduce therapy-refractory graft versus host disease in Allogeneic Hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation is often necessary to
prevent disease relapse in patients with hematologic malignancies such as
leukemia or lymphoma. The goal of the precedure is to elecit a
graft-versus-tumor response to prevent relapse of the malignancy. This
procedure is performed several hundred times per year in the Netherlands, but
there is a large mortality and moribidity risk, of which graft-versus-host
disease is the most developed. About 70% of allogeneic HSCT recipients develop
some form of GvHD. In particular severe GvHD of the intestine has a high
mortality risk (50% for the whole group, with a 2 year survival for
therapy-refractory GvHD patients of <20%) Recently the intestinal microbiota
has gained interest as drivers of the pathophysiology of both hematological
(GVHD) and autoimmune disease such as Crohn's disease and ulcerative colitis.
Recent studies have suggested that fecal transplantation (using feces from
healthy donors) can affect disease state of IBD patients and animal data have
suggested that the same holds true for GVH disease. We therefore postulate
that fecal transplantatie can have beneficial effects on intestinal GVH in
patients that received allogenic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation is often complicated by
graft versus host disease (GvHD) causing high morbidity and mortality. Loss of
gutmicrobial diversity is a risk factor to develop GvHD. We will test the
hypothesis that restitution of normal microbial diversity by fecal microbiota
transplantation may cure therapy-refractory gastro-intestinal GvHD.

single center, single arm, non-randomized intervention trial

fecal transplantation from healthy screened donors

In theory there is a risk of transferring infectious diseases (in line with
bloodtransfusion), however due to thorough screening of fecal donors (together
with prof Nieuwdorp) this risk will be minimized. Signoid biopsies will be
taken under local anesthesia and has no great risks in this patient group. As
fecal transplant was safe in > 400 patients at AMC including other
immunocompromised patients (kidney transplant patients) , we believe that the
gained insight in the pathophysiology of and potential treatment of intestinal
GVH with healthy donor feces or specific bacterial strains will outweight the
potential side effects such as infection/sepsis (that can be treated with
antibiotics if necessary).