父母供者外周血单倍体干细胞移植治疗儿童复发难治急性白血病

Parental peripheral blood haploidentical hematopoietic stem cell transplantation in treatment of children with relapsed and refractory acute leukemia

背景:儿童复发难治急性白血病单纯化学治疗效果极差,异基因造血干细胞移植是治愈该类疾病的惟一有效方法。研究显示单倍体移植与同胞相合及非亲缘全相合造血干细胞移植的治疗效果接近,甚至优于后者,且父母作为供者单倍体造血干细胞移植依从性好,能够保证移植干细胞数量及预防原发病复发,明显提高了患者移植成功率及长期无白血病生存率。目的:回顾分析父母供者单倍体外周血造血干细胞移植治疗儿童复发难治急性白血病的疗效。方法:入选35例父母供者外周血单倍体造血干细胞移植治疗儿童复发难治急性白血病。均采用"改良1,4-丁二醇二甲磺酸酯/环磷酰胺+胸腺细胞免疫球蛋白"预处理方案和环孢素、吗替麦考酚酯及甲氨蝶呤三联短程预防移植物抗宿主病。结果与结论:35例父母供者外周血单倍体造血干细胞移植治疗儿童复发难治急性白血病均植入成功。135例患儿回输单个核细胞中位数为5.82(3.23-8.45)×108/kg,其中CD34+细胞中位数为4.52(2.37-11.51)×106/kg。2干细胞回输后100 d内,移植相关死亡率为14.3%。33-Ⅱ度急性移植物抗宿主病发生率为34.3%,Ⅲ-Ⅳ度急性移植物抗宿主病发生率为37.1%,慢性移植物抗宿主病总发生率为42.9%。42年无白血病生存率为42.9%,2年总生存率为51.4%,2年原发病复发率为34.3%,中位生存时间为24个月。提示对于无人类白细胞抗原相合同胞供者及不能及时寻找到非血缘人类白细胞抗原相合供者的儿童复发难治急性白血病,父母供者外周血单倍体造血干细胞移植是一种高效可行的治疗方法。

BACKGROUND： Children with relapsed and refractory acute leukemia have a very poor clinical effect by simple chemotherapy, and allogeneic hematopoietic stem cell transplantation is the only effective approach to cure the disease. Haploidentical hematopoietic stem cell transplantation is becoming gradually mature, and the data show it has gotten better clinical efficacy than identical sibling and unrelated matched hematopoietic stem cell transplantation. In addition, parents have high compliance in order to save the treatment interval, which ensures the stem cell number and prevents leukemia recurrence, significantly improving the transplantation success rate and long-term leukemia-free survival rate. OBJECTIVE： To retrospectively analyze the clinical efficacy of parental peripheral blood haploidentical stem cell transplantation in treating children with relapsed and refractory acute leukemia. METHODS： Thirty-five children with relapsed and refractory acute leukemia undergoing parental peripheral blood haploidentical stem cell transplantation were enrolled. ＂Modified 1,4-butanediol dimethanesulfonate/ cyclophosphamide＋thymocyte immunoglobulin＂ conditioning regimen and triple therapy of methotrexate, cyclosporine A and mycophenolate mofetil were applied to prevent graft-versus-host disease. RESULTS AND CONCLUSION： All the 35 patients achieved full engraftment.（1） The median mononuclear cellswas 5.82（3.23-8.45）×108/kg, the median CD34＋ cells was 4.52（2.37-11.51）×106/kg.（2） Within 100 days after stem cell infusion, the transplant related mortality was 14.3%.（3） Incidence of I-II degrees of acute graft-versus-host disease was 34.3%, III-IV incidence was 37.1%, and the total incidence of chronic graft-versus-host disease was 42.9%.（4） The 2-year leukemia-free survival rate was 42.9%; the 2-year overall survival rate was 51.4%; the leukemia relapse rate was 34.3%; median survival time was 24 months. Results show that if there are no human leukocyte antigen-identical sibling and unrelated human leukocyte antigen-matched donors, parental haploidentical peripheral blood stem cell transplantation is an effective and feasible treatment for children with relapsed and refractory acute leukemia.