氟达拉滨联合阿糖胞苷化疗治疗异基因造血干细胞移植后急性白血病复发

目的 观察氟达拉滨联合阿糖胞苷(FA方案)大剂量化疗对异基因造血干细胞移植(allo-HSCT)后急性白血病复发的治疗效果.方法 急性白血病患者10例,7例接受亲缘供者造血干细胞移植,3例接受非亲缘供者造血干细胞移植,所有患者移植后均获得造血重建,为完全供者型.10例于首次移植后38～213 d(中位数为126 d)急性白血病复发,其中完全供者型复发1例,完全受者型复发4例,混合嵌合体型复发5例.原发病复发后均采用FA方案化疗,氟达拉滨用量为25 mg/m2,阿糖胞苷用量为1.5 g/m2,用5 d,其中6例于化疗结束后第2天还接受原供者外周造血干细胞(PBSC)移植,未使用预防移植物抗宿主病(GVHD)的药物.结果 除1例早期(8 d)死亡外,其余9例再次获得造血重建,经外周血DNA序列分析证实为完全供者型.获得造血重建的9例,4例由于复发、感染、多脏器功能衰竭等原因死亡,5例无病存活至随访结束,存活时间分别为585、442、405、213和243 d.治疗后,3例未发生GVHD,其余7例发生急性或慢性GVHD;7例并发肺部真菌感染,3例并发出血性膀胱炎,4例并发巨细胞病毒血症.10例的6个月实际无病存活率为60%,2年预期无病存活率为53%.结论 对于allo-HSCT后的急性白血病复发,采用FA方案化疗,如条件允许联合原供者造血干细胞输注,可能是目前可采取的一种有效治疗方案.

Fludarabine combined with cytarabine for treating relapse of acute leukemia after allogeneic hematopoietic stem cell transplantation

Objective To investigate the clinical efficacy of fludarabine combined with cytarabine (FA) in treating the relapse of acute leukemia after allogeneic stem cell transplantation (allo-HSCT). Methods Ten patients with relapse of acute leukemia after allo-HSCT were retrospectively analyzed. Among the patients, PBSCs were from 7 related donors and 3 unrelated donors. After the transplantation, the median relapse time was 126 days (range,38～213 days). Two days after the FA chemotherapy, 6 patients received infusion of the same donor's peripheral blood stem cells, and the median number of CD34+ cells was 3.5×106/kg(1.8～4.2)×106)], mobilized by granulocyte colony stimulating factor. No prophylactic agents for graft versus host diseases were administered. Results One patient who had received FA treatment and the donor's stem cell transfusion failed to acquire hematopioetic reconstitution and died 8 days after the PBSC transfusion, and the remaining 9 patients successfully got hematopioetic reconstitution of full donor chimera. Bone marrow hematological complete remission and full donor chimera were verified 30 days after the treatment in the 9 cases. Of the total 10 patients,graft versus host disease occurred in 7,and 2 of them received no donor's stem cell infusion (DSI). Seven patients suffered from pulmonary funsal infection, 3 from haemorrhagic cystitis, and 2 from cytomegalovirus viraemia. Five patients died and 5 survived with DFS till to the follow-up endpoint. The survival time for the 5 patients with DFS was 585,442, 405,213 and 243 days, respectively. The 6-month DFS rate was 60 % and the estimated 2-year DFS rate was 53 %. Conclusion FA chemotherapy, combined with reinfusion of donor's PBSC if possible, could serve as an possible effective therapeutic method for leukemia relapse after allo-HSCT.