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.