Gut immunomodulation with vedolizumab prior to allogeneic hematopoietic stem cell transplantation in pediatric patients with inflammatory bowel disease.

BACKGROUND: Inborn errors of immunity (IEI) are often associated with inflammatory bowel disease (IBD). IEI can be corrected by allogeneic hematopoietic stem cell transplantation (HSCT) however peri-transplantation intestinal inflammation may lead to increased risk of gut graft-versus-host disease (GVHD). Vedolizumab inhibits the homing of lymphocytes to the intestine and may attenuate gut GVHD, yet its role in preventing GvHD in pediatric patients with IEI-associated IBD has not been studied.

OBJECTIVE: To describe a cohort of pediatric patients with IEI-associated IBD treated with vedolizumab before and peri allogeneic HSCT.

DESIGN/METHOD: Retrospective chart review of pediatric patients with IEI-associated IBD treated with vedolizumab 6, 4, and 1 week(s) before receiving HSCT. The conditioning regimen consisted of treosulfan, fludarabine and cyclophosphamide with rabbit antithymocyte globulin, with tacrolimus and steroids as GVHD prophylaxis.

RESULTS: Eleven patients (6 females) with a median age of 5 years (range: 0.4-14 years) with diverse IEI were included. IBD symptoms were characterized by abdominal pain, loose stools and blood in stools. Four patients had developed perianal fistula and 1 had a rectal prolapse. 1 patient had a G tube and a Jejunal tube in situ. IBD treatment before HSCT included steroids (n=11), anakinra (n=2), infliximab (n=4), sulfasalazine (n=2), mesalazine (n=2) and Vedolizumab. IBD symptoms were considered controlled in the absence of abdominal pain, loose stools or blood in stools. Graft sources were unrelated donor cord (n=5; 2 with 5/8, 2 with 7/8 and 1 with 6/8 HLA match), Peripheral blood stem cells (n=5; 2 haploidentical, 1 with 9/10 and 2 with 10/10 HLA match) and bone marrow (n=1; 10/10 matched sibling). The median number of vedolizumab infusions pre- and post-HSCT were 4 (range: 3-12), and 1 (range:1-3) respectively and all were reported to be uneventful. All patients had engrafted. Acute GVHD occurred in 4 patients and was limited to grade 1 skin only. Chronic GVHD occurred in one patient and again was limited to the skin only. There was no gut GVHD. Three and two patients experienced Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) viremia respectively. All patients are alive with no evidence of IBD at a median follow-up of 15 months (range: 3-39 months).

CONCLUSION: Administration of vedolizumab pre- and post-HSCT in pediatric patients with IEI-associated IBD is well tolerated and associated with a low rate of gut GVHD. These findings provide a platform for prospective study and use of vedolizumab for GVHD prophylaxis in pediatric patients with known intestinal inflammation as comorbidity pre-transplant.