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

Abstract

Background & aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Allogeneic HSCT; Inborn Errors of Immunity; Monogenic IBD; VEO-IBD.

Figure 1.

(A) Cohort data. Created in BioRender. (B) Age of onset of gastrointestinal symptoms.

Figure 2.

Disease activity scores at the time of IBD presentation, immediately prior to transplant, 1-year post-transplant, and at most recent follow up if ≥2 years since transplant.

Figure 3.

Location of macroscopic gastrointestinal disease (dark gray) and isolated microscopic inflammation (light gray) based on endoscopy and/or imaging in individual patients prior to HSCT. Paris classification behavior was included for those with Crohn’s disease. White, non-affected region; Black, not evaluated prior to transplant.

Figure 4.

Secondary outcomes. Percentage of patients with infection pre-transplant (A) and post-transplant (B). (C) Number of hospitalization days in the years prior to HSCT compared with the number of days spent in the hospital from years 1 to 2 post-transplant. N = 18 patients with ≥2 years of follow up data. *P < .05 (D) Change in height Z-score from time of transplant to most recent follow-up.