单倍型异基因造血干细胞移植后大剂量环磷酰胺诱导免疫耐受治疗儿童重型再生障碍性贫血

High-dose cyclophosphamide-induced immunogenic tolerance following haploidentical allogeneic hematopoietic stem cell transplantation in severe aplastic anemia children

BACKGROUND:High-dose cyclophosphamide (CTX)-induced immunogenic tolerance following haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) is developed to optimize the treatment of childhood severe aplastic anemia (SAA) using haplotype allo-HSCT, providing a theoretical basis for the clinical application.OBJECTIVE:To investigate the clinical efficacy and safety of the use of high-dose CTX following haploidentical allo-HSCT in SAA children. METHODS:Clinical data from 10 children with SAA undergoing haploidentical allo-HSCT at the Department of Hematology, General Hospital of Beijing Military Area from January 2013 to January 2015 were retrospectively analyzed. Pretreatment was CTX, fludarabine, Busulfex combined with anti-human lymphocyte immune globulin used for 2 consecutive days, and then 3 days after transplantation, CTX (50 mg/kg per day) was used to induce immunogenic tolerance. Combined use of cyclosporin A, methotrexate and tacrolimus functioned as a prophylaxis for graft-versus-host disease. Another 10 SAA children who underwent synchronous HLA-identical sibling HSCT served as controls. Complications and survival in children were statistically analyzed in the two groups.RESULTS AND CONCLUSION:In the treatment group, children were followed up until May 2015, and the median follow-up period was 18.1 months (5-28 months). Hematopoietic reconstruction was successful in all cases, and there were three cases of graft-versus-host disease, three cases of pulmonary infection and two cases dying of pulmonary infection. In the control group, the median follow-up period was 20.7 months (6-27 months), and all the children received hematopoietic reconstruction. Additionally, there were two cases of graft-versus-host disease, four cases of pulmonary infection, one case dying of graft-versus-host disease and one case dying of pulmonary infection in the control group. The total survival rate in each group was 80%. In summary, high-dose CTX-induced immunogenic tolerance is safe and effective for SAA children undergoing haploidentical allo-HSCT, which makes the clinical efficacy of haploidentical allo-HSCT identical to that of matched HSCT.