单倍型异基因造血干细胞移植治疗儿童复发难治性急性淋巴细胞白血病的临床研究

Clinical study of haploid allogeneic hematopoietic stem cell transplantation in the treatment of children with relapsed or refractory acute lymphoblastic leukemia

目的 探讨单倍型异基因造血干细胞移植（allo-HSCT）治疗儿童复发难治性急性淋巴细胞白血病（ALL）的疗效和安全性.方法 选择北京军区总医院血液科2010年1月至2013年1月采用allo-HSCT治疗的儿童复发难治性ALL患者20例,其中男12例,女8例,中位年龄9岁（1～ 14岁）;B-ALL 14例,T-ALL 6例;移植时复发未缓解10例,复发后取得2次或者3次缓解10例;6例采用骨髓加外周血干细胞联合移植,14例仅采用外周血干细胞移植;预处理方案主要为白消安、氟达拉滨、环磷酰胺、抗胸腺细胞免疫球蛋白,部分患儿加用阿糖胞苷、依托泊苷或司莫司汀及接受全身照射等.移植物抗宿主病（GVHD）的预防采用环孢素、吗替麦考酚酯、甲氨蝶呤（＋1、＋3、＋6、＋11天）.移植后观察患儿不良反应、并发症和无病生存等情况.结果 全部患儿均获重建造血,移植后1个月供者细胞嵌合率均为100％.移植后粒细胞植活中位时间为12.5d（9～23d）,血小板植活中位时间为15d（12～40d）.随访至2014年6月,中位随访时间25个月（2 ～ 50个月）,8例发生急性GVHD,11例发生慢性GVHD,因GVHD死亡2例,感染死亡1例,复发死亡2例,共死亡5例,其余15例患儿生存,全组患者的总体生存率为75％.结论 单倍型allo-HSCT治疗儿童复发难治性ALL安全可行,长期生存率提高,移植后并发症及复发率并未增加.

Objective To explore efficacy and safety of haploid allogeneic hematopoietic stem cell transplantation （allo-HSCT） for the children with relapsed or refractory acute lymphoblastic leukemia.Methods 20 cases of childhood acute lymphoblastic leukemia treated with haploid allo-HSCT were collected in Beijing Military General Hospital Hematology from Jan 2010 to Jan 2013,including 12 males and 8 females,with median age 9 （1-14） years old.There were 14 cases of B-ALL and 6 cases of T-ALL.When transplation,10 cases were relapsed without remission,and 10 cases were relapsed after 2 or 3 times to obtain remission.6 cases received bone marrow plus peripheral blood stem cell transplantation,and 14 cases received peripheral blood stem cell transplantation.Pretreatment program mainly were busulfan （Bu）,fludarabine （Flu）,cyclophosphamide （CTX） and anti-thymocyte immunoglobulin （ATG）,plus cytarabine,etoposide or semustine and total body irradiation in some patients.Graft-versus-host disease （GVHD） was prevented by cyclosporine （CsA）,mycophenolate mofetil （MMF） and methotrexate （MTX） （＋1,＋3,＋6,＋11 day）.After transplantation,adverse reactions,complications and disease-free survival were observed.Results The hematopoiesis in all of children were rebuilded,and 1 month after transplantation,donor cells chimeric rate was 100 %.After transplantation,the median time of granulocyte plant alive was 12.5 d （9-23 d）,and that of platelet plant alive was 15 d （12-40 d）.Follow-up until Jun 2014,the median follow-up time was 25 months （2-50 months） with 8 cases of acute GVHD,11 cases of chronic GVHD,and 5 cases of death including GVHD in 2 cases,infection in 1 case and recurrence in 2 cases.The overall survival rate was 75 % （15/20）.Conclusion Haploid allo-HSCT for children with recurrent refractory lymphocytic leukemia scheme is safe,which could improve the long-term survival rate without increasing the complications and recurrence rate after transplantation.