Objective: 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 CAGlike 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）.
Conclusion: 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.
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。