小剂量地西他滨用于高危急性淋巴细胞白血病移植后维持治疗的临床观察

Clinical observation of maintenance treatment with low-dose decitabine after transplantation for patients with high-risk acute lymphoblastic leukemia

目的探讨小剂量地西他滨用于高危急性淋巴细胞白血病(ALL)异基因造血干细胞移植(allo-HSCT)后维持治疗的疗效和安全性.方法收集2016年7月至2018年3月于郑州大学第一附属医院行allo-HSCT的10例高危ALL并在移植后给予小剂量地西他滨维持治疗的患者资料,分析其移植后复发和移植物抗宿主病(GVHD)的发生情况并评估该方案的安全性,同时使用Kaplan-Meier法分析累积复发率、无病生存(DFS)率和总生存(OS)率.结果共2例患者复发,10例患者的中位复发时间为移植后575 d,1年累积复发率16.7%,1年OS率100.0%,1年DFS率83.3%.2例伴p53突变患者截至随访结束移植后DFS时间分别达23个月和11个月.未观察到因使用地西他滨而诱发或减轻GVHD的现象.9例患者发生Ⅰ~Ⅱ级骨髓抑制.3例发生移植后不明原因血小板减少,地西他滨治疗后血小板均恢复正常.结论小剂量地西他滨维持治疗血液学不良反应小,在不增加GVHD的同时,可作为高危ALL患者移植后预防复发的维持治疗选择.

Objective To investigate the efficacy and safety of maintenance treatment with low-dose decitabine after allogeneic stem cell transplantation (allo-HSCT) for high-risk acute lymphoblastic leukemia (ALL). Methods The data of 10 patients with high-risk ALL who received maintenance therapy with low-dose decitabine after allo-HSCT in the First Affiliated Hospital of Zhengzhou University from July 2016 to March 2018 was collected. The incidence of post-transplant relapse and graft-versus-host disease (GVHD) and the safety of the treatment protocol were analyzed. The cumulative incidence of relapse (CIR) rate, disease-free survival (DFS) rate and overall survival (OS) rate were estimated by Kaplan-Meier method. Results Two patients relapsed and the median relapse time of these 10 patients was 575 days after transplantation. The 1-year CIR, OS and DSF rates were 16.7%, 100.0% and 83.3%, respectively. At the end of follow-up, the DFS time after transplantation of 2 patients with p53 mutation were 23 months and 11 months, respectively. There was no induction or alleviation of GVHD caused by decitabine treatment. Nine patients developed grade Ⅰ-Ⅱmyelosuppression. Three patients had unexplained thrombocytopenia after transplantation and their platelet counts recovered after decitabine treatment. Conclusion Maintenance therapy with low-dose decitabine has low hematologic toxicity without increasing GVHD, which could be a maintenance treatment option to prevent relapse after transplantation for patients with high-risk ALL.