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

doi:10.3969/j.issn.2095-4344.2016.32.016

Abstract：BACKGROUND:High-dose cyclophosphamide (CTX)-induced immunogenic tolerance folowing haploidentical alogeneic hematopoietic stem cel transplantation (alo-HSCT) is developed to optimize the treatment of childhood severe aplastic anemia (SAA) using haplotype alo-HSCT, providing a theoretical basis for the clinical application. <br> OBJECTIVE:To investigate the clinical efficacy and safety of the use of high-dose CTX folowing haploidentical alo-HSCT in SAA children. <br> METHODS:Clinical data from 10 children with SAA undergoing haploidentical alo-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 statisticaly analyzed in the two groups. <br> RESULTS AND CONCLUSION:In the treatment group, children were folowed up until May 2015, and the median folow-up period was 18.1 months (5-28 months). Hematopoietic reconstruction was successful in al 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 folow-up period was 20.7 months (6-27 months), and al the children received hematopoietic reconstruction. Additionaly, 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 alo-HSCT, which makes the clinical efficacy of haploidentical alo-HSCT identical to that of matched HSCT.