Multi-center Clinical Study of Cord Blood Stem Cell Transplantation in The Treatment of Very Early-Onset Inflammatory Bowel Disease Caused by Interleukin-10 Receptor Gene Deficiency

Very early onset inflammatory bowel disease (VEO-IBD) is a special subtype of children's inflammatory bowel disease (IBD). The clinical characteristics of VEO-IBD patients include early onset, severe diarrhea, severe malnutrition, perianal diseases and repeated infection. Studies have found that VEO-IBD is mostly caused by single-gene defects and can be cured by allo-hematopoietic stem cell transplantation ( HSCT). VEO-IBD is a rare disease. At present, there is no large sample of clinical data for transplantation in these patients. Umbilical Cord Blood Transplantation (UCBT) is less reported. Therefore, many transplantation-related issues need to be further studied, including HSCT indications, transplantation timing, pre-transplantation drug therapy, intestinal protection during transplantation, prevention and treatment of post-transplantation complications and so on. The aim of this study is to investigate the efficacy of UCBT in the treatment of VEO-IBD caused by interleukin-10 receptor (IL10R) gene deficiency, including engraftment rate, disease-free survival rate and overall survival rate, and to evaluate transplant-related mortality and complications. All the selected cases are diagnosed as VEO-IBD with IL10R gene deficiency by enteroscopy, histopathology and gene detection. These patients have no matched sibling donors. Their organs function should be normal. The guardian of the patient has the desire and requirement for UCBT and signs the informed consent before treatment. Cord blood stem cell selection: HLA high-resolution detection of patients before transplantation, searching through cord blood stem cell bank, selecting cord blood stem cells that meet the following criteria: HLA-A, B, C, DRB1 high-resolution (genotype) > 6/8 matching, total number of nuclear cells > 5 x 10^7/kg. Conditioning regimen: fludarabine + busulfan + cyclophosphamide. GVHD prevention: tacrolimus (FK506) or cyclosporine A. Infection prevention: Micafungin/caspofungin before engraftment, voriconazole after engraftment to prevent fungi. Ganciclovir is used from the beginning of conditioning to the infusion of cord blood stem cells, and acyclovir is used to prevent virus infection. SMZ is used to prevent Pneumocystis carinii infection after engraftment until half a year after the withdrawal of immunosuppressive agents.

Procedure/Surgery: Cord Blood Stem Cell Transplantation Unrelated cord blood stem cell selection: HLA high-resolution detection should be performed before transplantation. High-resolution (genotype) matching of HLA-A, B, C and DRB1 should be selected. The total number of nuclear cells should be more than 5*107/kg.

Conditioning regime: fludarabine 30 mg/m2/d for 5 days, busulfan 1 mg/kg for 4 times for 3 days, cyclophosphamide 50 mg/kg for 2 days.

Prevention of GVHD: tacrolimus (FK506) 0.1 mg/kg/day, starting from day 4 before transplantation, taking orally twice on an empty stomach to monitor the blood concentration and keep it at 5-10 ng/ml.

Infection prevention: Micafungin/caspofungin before engraftment, voriconazole after engraftment to prevent fungi. Ganciclovir is used from the beginning of conditioning to the beginning of reinfusion, and acyclovir is used to prevent virus infection until immunosuppressive agents are discontinued after reinfusion. SMZ is used to prevents Pneumocystis carinii infection after engraftment.