Outcomes of Allogeneic Hematopoietic Stem Cell Transplant in Monogenic Inflammatory Bowel Disease

Monogenic inflammatory bowel disease (IBD) can result in inborn errors of immunity and intestinal epithelial cell dysfunction, more commonly seen in patients with very early onset IBD (VEO-IBD). Hematopoietic stem cell transplant (HSCT) has emerged as an effective treatment for a subset of patients with monogenic IBD. We sought to evaluate the efficacy and safety of HSCT in these patients. We hypothesized that HSCT will lead to IBD medication-free remission or significant improvement of disease.

This was a single-center, retrospective study of children with monogenic IBD who underwent HSCT at The Children's Hospital of Philadelphia from 2012 to 2022. The primary outcome was IBD medication-free sustained remission, measured by disease activity index. Secondary outcomes included all-cause mortality, growth, hospitalizations, infections, and HSCT-associated complications.

Thirty-eight patients with monogenic IBD were identified as eligible for HSCT, with 25 undergoing HSCT as therapy for IBD during the study period. There was 100% survival at a median follow-up of 3 years. Prior to transplant, 76% of patients received immunosuppression, and 20% underwent IBD-related surgery. At most recent follow-up, 92% of patients achieved sustained medication-free remission of IBD and 60% with prior ostomy underwent re-anastomosis. There was significant improvement in growth, hospital days, and severe infections.

HSCT resulted in IBD medication-free remission and reduction in disease-associated complications. This highlights the strength of genetic evaluation in patients with VEO-IBD or refractory IBD and consideration of HSCT, which can be curative and lifesaving in patients with monogenic defects involving immune dysfunction.