地西他滨联合DAG方案等三种方案治疗复发、难治急性髓系白血病疗效的比较分析

Comparative analysis of decitabine combined with DAG regimen and other regimens in treatment of refractory/relapsed acute myeloid leukemia

目的 比较地西他滨联合DAG方案、CAG方案和“3＋7”标准方案治疗复发、难治急性髓系白血病（AML）的有效性及安全性.方法 收集2008年9月至2013年4月收治的67例复发、难治AML患者的临床资料,比较分析地西他滨联合DAG方案（DAG：柔红霉素＋阿糖胞苷＋G-CSF,地西他滨20 mg·m-2·d-1×3d,第4天起予以DAG方案）、CAG方案（阿克拉霉素、阿糖胞苷、G-CSF）和“3＋7”标准诱导方案（蒽环类药物联合阿糖胞苷）组患者的临床疗效及不良反应.结果 地西他滨联合DAG方案组19例,完全缓解（CR）5例（26.3％）,部分缓解（PR）4例（21.1％）,总有效率（ORR）为47.4％; CAG方案组26例,CR 8例（30.8％）,PR 1例（3.8％）,ORR为34.6％;“3＋7”标准方案组22例,CR4例（18.2％）,ORR为18.2％.三组ORR率两两比较,地西他滨联合DAG方案组显著优于“3＋7”标准方案组（P＜0.05）,余差异均无统计学意义（P＞0.05）.地西他滨联合DAG治疗获得CR的患者,治疗前骨髓原始细胞数显著低于非CR的患者（P＜0.05）.而CAG方案和“3＋7”标准方案治疗获得CR的患者与相应非CR患者相比,治疗前骨髓原始细胞数差异无统计学意义（P＞0.05）.三组患者出现的不良反应主要包括骨髓抑制、肺部感染、恶心呕吐和肝功能损害,经过输血和抗感染等支持治疗均可以耐受.随访至2013年9月,地西他滨联合DAG组、CAG组及“3＋7”组患者的中位生存时间（复发至随访终点）分别为7.5、4.0和3.0个月,地西他滨联合DAG组患者的生存时间明显长于“3＋7”组（P＜0.05）.结论 地西他滨联合DAG方案治疗老年、不适合大剂量化疗及移植的复发、难治AML患者临床疗效显著.治疗前骨髓原始细胞数较少的复发AML患者更适合应用地西他滨联合DAG方案.

Objective To compare the clinical efficacy and safety among different chemotherapeutic regimens in treatment of refractory/relapsed acute myeloid leukemia （AML）.Methods The clinical data of 67 refractory/relapsed AML patients enrolled from September 2008 to April 2013 were collected.The differences of clinical outcome and adverse events among the patients treated with decitabine combined with DAG regimen,CAG regimen or ＂3 ＋ 7＂ regimen were analyzed.Results Among 19 patients in decitabine treatment group,5 （26.3%） achieved complete remission （CR）,4 （21.1%） partial remission （PR）,with overall response rate （ORR） of 47.4 %.Of 26 patients in CAG regimen group,8 （30.8%） achieved CR,1 （3.8%） PR,with ORR of 34.6%.Of 22 patients in ＂3＋7＂ regimen group,4 （18.2%） achieved CR,with ORR of 18.2%.The ORR of decitabine group was significantly higher than that of ＂3＋7＂ group （P〈0.05）.However,no significant difference of ORR was observed among the three groups （P〉0.05）.It was interesting to note that in decitabine group,the marrow blast counts were lower in CR patients compared with those in non-CR patients （P〈0.05）,while this was not found in ＂3＋7＂ group （P〉0.05） and CAG regimen group （P〉0.05）.Adverse events in the three groups were similar,mainly including myelosuppression,pulmonary infection,nausea,vomiting and liver dysfunction,and could be well tolerated.Followed-up to September 2013,the median overall survival （OS） of decitabine group,CAG regimen group and ＂3＋7＂group after relapse was 7.5,4 and 3 months,respectively （P〉0.05）,while significant difference was obtained between decitabine group and ＂3 ＋ 7＂ regimen group （P〈0.05）.Conclusions Decitabine combined with DAG regimen is effective and well tolerated in refractory/relapsed AML patients who were unsuitable for intensive chemotherapy and hematopoietic stem cell transplantation,and the patients with low marrow blast counts are more suitable for the application of decitabine combined with DAG regimen.