亲缘单倍体造血干细胞移植治疗急性巨核细胞白血病的疗效及安全性分析

摘要

目的 探讨单倍型异基因造血干细胞移植(Haplo-HSCT)治疗急性巨核细胞白血病(AMKL)的疗效及安全性分析.方法 回顾性分析2013年2月-2018年4月我院收治14例AMKL患儿进行Haplo-HSCT的临床资料并复习相关文献.男性9例,女性5例,中位年龄2(1.4～3)岁,13例为第一次Haplo-HSCT,l例为非血缘全相合无关供者移植半年后复发挽救性二次移植.HLA配型均为父母亲单倍型.使用清髓性预处理方案,同时兼顾患儿个体实际情况制定的个体化方案.移植物为骨髓和/或外周血干细胞,输注单个核细胞中位数为10.2(2.3～12.7)×108/kg, CD34+细胞中位数为6.2(2.0～11.5)×106/kg,非血缘脐带血做为第三方细胞辅助治疗.结果 中性粒细胞、血小板重建的中位天数分别为14d和15d.28d评价供受者间基因嵌合率完全供者型占92％(12/13),1例移植后排斥,1例移植11d尚未植活,死于弥漫性肺出血.Ⅰ～Ⅳ度aGVHD发生率为61％(8/13),其中IE～Ⅳ度aGVHD3例,其中1例因aGVHD死亡,cGVHD累积发生率53％(7/13),其中广泛型cGVHD为0.CMV/EBV病毒激活率30％ (4/13).3例移植后早期复发(100d内),复发率为23％(3/13),9例患儿免疫残留持续阴性,为供者型完全嵌合,无病生存至今,存活的9例患者中位随访时间21(8～61)个月,总生存率为64％ (9/14).结论 AMKL单纯 依靠化疗预后差,Haplo-HSCT可以改善AMKL患儿预后,提高生存率,但仍有部分患儿早期复发, 减少复发的手段值得进一步探讨.%Objective To investigate the efficacy of haplotype allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) in the treatment of acute megakaryocytic leukemia (AMKL). Methods Clinical data about Haplo-HSCT of 14 children with AMKL admitted in Bayi Children's Hospital Affiliated to Army General Hospital from February 2013 to April 2018 were analyzed retrospectively and related literatures were reviewed . There were 9 males and 5 females, the median age was 2 (ranged 1.4-3) years old. 13 cases were treated with Haplo-HSCT for the first time. One case is recurrent rescue secondary transplantation of a non-blood matched unrelated donor after six months. All HLA matching types were parental haplotypes. The actual situation of the individual program was taken into account when myeloablative preconditioning regimen was used. The transplant was bone marrow and / or peripheral blood stem cell. The median of mononuclear cells infused was 10. 2(2. 3-12. 7) × 108/kg. The median of CD34 + cells was 6.2(2.0-11.5)×106/kg. Unrelated cord blood was used as a third-party cell adjuvant therapy. Results The median days of neutrophil and platelet reconstruction were 14 days and 15 days, respectively. Complete donor type of gene chimerism rate among donor recipients within 28 days accounted for 92％ (12/13). There was 1 case of rejection after transplantation. One case which had not been alive after being transplanted for 11 days died of diffuse pulmonary hemorrhage. The incidence of Ⅰ -Ⅳ aGVHD was 61％ , among which 3 cases were IE-Ⅳ severe aGVHD. One case died from aGVHD. Cumulative incidence of chronic GVHD was 53％ (7/13). The prevalence of chronic GVHD was 0. The activation rate of CMV / EBV virus was 30％ (4/13). There were 3 cases of early recurrence after transplantation(within 100 days). The recurrence rate was 23％ (3 /13). There are now 9 children with persistent negative immune residue which was donor complete chimerism. They survived till now. The median follow-up time of 9 surviving patients was 21 (8-61) months, and the overall survival rate was 64％ (9/14). Conclusions AMKL has poor prognosis only be treated by chemotherapy. Haplo-HSCT can improve prognosis of patients with AMKL and improve survival rate. However, there are still some patients with early recurrence, the method of reducing recurrence is worth further exploring.