摘要目的 观察地西他滨联合预激方案再诱导治疗伴DNA甲基转移酶(DNMT3A)基因突变的复发难治正常核型急性髓系白血病(CN-AML)的疗效.方法 回顾性分析2011年4月至2014年10月接受地西他滨联合预激方案再诱导治疗的53例复发或难治CN-AML患者的临床特征及对地西他滨联合预激方案的治疗反应,其中伴DNMT3A基因突变(DNMT3A+)24例,不伴DNMT3A基因突变(DNMT3A-)29例.结果 DNMT3A+组患者中位年龄为46(26～68)岁,与DNMT3A-组差异无统计学意义,WBC中位数19.5 (0.5～218.5)×109/L,骨髓原始细胞中位数0.635(0.020～0.920),较DNMT3A-组高,但差异亦无统计学意义(P值均＞0.05).DNMT3A+患者对地西他滨联合预激方案治疗的总体反应率(ORR)达62.50％,完全缓解(CR)率为54.17％,DNMT3A组分别为48.28％和37.93％,两组相比差异无统计学意义(P值分别为0.407、0.277).两组患者应用地西他滨联合预激方案再诱导治疗的不良反应类似.53例患者中,共有29例患者伴有FLT3-ITD突变,FLT3-ITD+/DNMT3A+组(14例)与FLT3-ITD+/DNMT3A-组(15例)的ORR及CR率差异有统计学意义(P值分别为0.040、0.042).DNMT3A+组与DNMT3A-组1年总生存(OS)率分别为59.58％和54.09％,差异无统计学意义(P=0.438).后期25例患者行异基因造血干细胞移植,DNMT3A+ CN-AML患者1年OS率为87.50％,1年无病生存(DFS)率为72.73％;DNMT3A-组1年OS率为61.54％,1年DFS率为58.02％;两组差异无统计学意义(P值分别为0.456、0.217).结论 地西他滨联合预激方案是复发难治CN-AML有效且安全的再诱导治疗手段,FLT3-ITD+/DNMT3A+组CN-AML患者对地西他滨联合预激方案的反应率优于FLT3-ITD+/DNMT3A-组.地西他滨桥接allo-HSCT可以提高CN-AML患者的OS率.

abstractsObjective To study clinical characteristics of refractory or relapsed DNMT3A + cytogenetically normal acute myeloid leukemia (CN-AML) patients, and to explore the overall response rate (ORR) and side effects of these patients followed the therapy including decitabine with CAG or CAG-like regimen.Methods In this study we retrospectively analyzed 53 refractory or relapsed CN-AML patients receiving the therapy including decitabine combined with CAG and CAG-like regimen in our center from April 2011 to October 2014.The clinical characteristics and ORR were further analyzed.Based on gene mutations, these patients could be divided into 2 groups: DNMT3A+ AML patients (n=24) and DNMT3A-AML patients (n=29).Results The median age of DNMT3A+ AML patients was 46 years old, higher white blood cells and bone marrow blasts were observed in DNMT3A+ AML group.The ORR and complete response (CR) rate of DNMT3A+ group were 62.50％ and 54.17％, respectively.No differences were observed in ORR and CR rates (P＞0.05)between these two groups.DNMT3A+/FLT3-ITD+ CN-AML patients (n=14) had higher ORR and CR rates than DNMT3A-/FLT3-ITD+CN-AML patients (n=15) (P=0.040 and 0.042, respectively).The one-year overall survival (OS) of DNMT3A + AML group and DNMT3A-AML group were 59.58％, 54.09％, no differences were observed (P=0.438).25 patients received further therapy of allo-HSCT, the one-year OS of DNMT3A+ CN-AML was 87.50％ and one-year disease free survival (DFS) was 72.73％, while the one-year OS was 61.54％ and one-year DFS was 58.02％ in DNMT3A-group.No differences were observed between 2 groups (P=0.456, 0.217).Conclusions Decitabine combined with CAG or CAG-like regimen was an effective and safe treatment for refractory or relapsed CN-AML patients.Compared to DNMT3A-/FLT3-ITD + CN-AML patients, DNMT3A+/FLT3-ITD+ CN-AML patients had higher ORR and CR rates.Decitabine bridged hematopoietic stem cells transplant could likely improve the survival of refractory or relapsed CN-AML patients.