Severe combined immunodeficiency (SCID) is a rare disease caused by a group of genetic disorders that leads to early death from recurrent infections in affected children.The only curative therapy for SCID is allogeneic hematopoietic stem cell transplantation.Unrelated umbilical cord blood(UCB) is increasingly used as an alternative to bone marrow.
Severe combined immunodeficiency (SCID) is a rare disease caused by a group of genetic disorders that leads to early death from recurrent infections in affected children.The only curative therapy for SCID is allogeneic hematopoietic stem cell transplantation.Unrelated umbilical cord blood(UCB) is increasingly used as an alternative to bone marrow.The development of NBS in Europe and America has enabled more SCID patients to be diagnosed before symptoms appear, and to enter the normative assessment and intervention procedures as soon as possible. In China SCID has not been included in the NBS program,and there are few units that can diagnose SCID.Patients often delay diagnosis and miss the best period of transplantation. Department of Hematology, Children's Hospital of Fudan University, has used UCBT for the treatment of SCID patients with reduced intensity conditioning(RIC)since 2014.6 of 8 cases were treated with disease-free survival. The encouraging efficacy of these patients suggests that RIC of UCBT may be an effective treatment for SCID patients to urgently hematopoietic stem cell transplantation. The aim of this study is to investigate the efficacy of UCBT in the treatment of SCID, including engraftment rate, disease-free survival rate,overall survival rate and immune reconstitution, and to evaluate transplant-related mortality and complications. All the selected cases are diagnosed as severe combined immunodeficiency disease by immunological function 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) \> 6/8matching,total number of nuclear cells \>5x10\^7/kg.Conditioning: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 prevents Pneumocystis carinii infection after engraftment until half a year after the withdrawal of immunosuppressive agents. This is a multicenter prospective observational study. Procedure/Surgery: Cord Blood Stem Cell Transplantation Unrelated cord blood stem cell selection: HLA high-resolution detection is performed before transplantation. High-resolution (genotype) matching of HLA-A, B, C and DRB1 was selected. The total number of nuclear cells is more than 5\*107/kg. Reduced intensity conditioning : Busulphan 3.2mg/kg per day in divided doses for 3 days(total dose 9.6 mg/kg) and cyclophosphamide 50 mg/kg for 2 days (total dose 100 mg/kg). GVHD prevention: tacrolimus (FK506) 0.1 mg/kg/day, started 4 days before transplantation, is taken orally twice, and the blood concentration is monitored to maintain the concentration at 5-10 ng/ml. If the patient does not have a GVHD transplant +100 days after the slow reduction, until the transplant 6 months after the withdrawal. Infection prevention: Micafungin/caspofungin before engraftment, voriconazole after engraftment to prevent fungi. Ganciclovir is used from the beginning of pretreatment to the beginning of reinfusion, and acyclovir is used to prevent virus infection until immunosuppressive agents are discontinued after reinfusion. SMZ prevents Pneumocystis carinii infection after engraftment.
Study Type
OBSERVATIONAL
Enrollment
50
Unrelated cord blood stem cell selection； Reduced intensity conditioning； GVHD prevention； Infection prevention.
Children's Hospital of Fudan University
Shanghai, Minhang, China
Overall survival rate
Overall survival is defined as the survival status of patients by the end of 3 years after the transplanting, coded as 1 for dead and 0 for survive.
Time frame: 3 years after transplantation
Disease free survival rate
Disease free survival is defined as the survival status of patients by the end of the third year after transplantation. Disease free survival is defined as survive without conditions including engraftment failure and death caused by any reasons. The variable is coded as 0 for disease free survive, and 1 for all conditions other than the defined status of "0".
Time frame: 3 years after transplantation
Successful engraftment
The event of successful engraftment is defined as Neutrophil count ≥ 0.5×10\^9/L for continuous 3 days and platelet count ≥ 20×10\^9/L for continuous 7 days without transfusion. It is coded as 1.
Time frame: 3 years after transplantation
Immune reconstitution
Immune reconstitution is including T-cell and B-cell reconstitution.The variable would be coded as 1 if any of these two cells had been reconstituted while 0 for none. T-cell reconstitution is defined as meeting these criteria: CD3+ cell count \> 1000 per cubic millimeter, and CD4+ cell count \> 500 per cubic millimeter. B-cell reconstitution is defined as independence from Ig-replacement therapy.
Time frame: 3 years after transplantation
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