Treatment of IL-10RA deficiency of pediatric patients with very early onset inflammatory bowel disease by allogeneic haematopoietic stem cell transplantation

Very early onset inflammatory bowel disease (VEO-IBD) with interleukin-10 receptor-A (IL-10RA) defects is characterised by severe and unmanageable intestinal inflammation, perianal lesions, and a high mortality rate, with the onset of the disease occurring at a very early age. Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most effective treatments for VEO-IBD patients with IL-10 signaling deficiency. The objective of this study was to evaluate the clinical effectiveness of allo-HSCT in the treatment of children with VEO-IBD and IL-10RA deficiency, and to provide further clinical insights. A retrospective analysis and summary of the clinical data of seven patients with VEO-IBD and IL-10RA deficiency from January 2021 to December 2023 was performed. These patients subsequently underwent allo-HSCT after receiving a reduced-intensity conditioning regimen followed by a cyclosporine-based regimen for the prevention of graft versus host disease (GVHD). Hematopoietic reconstruction was performed on seven children with VEO-IBD combined with IL-10RA deficiency. Four patients developed grade I-II GVHD, while three patients developed grade III-IV GVHD after undergoing allo-HSCT. At a median follow-up of 518 days after allo-HSCT (range: 210-1072 days), six patients were alive, while one patient died 16 months after the procedure because of chronic GVHD and severe infections. The 3-year cumulative overall survival (OS) probability rate was 80.0% (95% CI: 44.7-100.0). All VEO-IBD patients demonstrated weight gain following HSCT, with substantial improvements observed in severe malnutrition and growth retardation associated with IL-10RA deficiency post-transplantation. Allo-HSCT is thus identified as the optimal curative therapy for VEO-IBD patients with IL10-RA deficiency. The importance of early multidisciplinary intervention and co-management of VEO-IBD is paramount in improving HSCT outcomes.