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地西他滨联合预激方案治疗53例复发难治正常核型急性髓系白血病的疗效分析

Outcomes of refractory or relapsed DNMT3A+ cytogenetically normal acute myeloid leukemia patients followed the therapy including decitabine combined with CAG or CAG-like regimen

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.

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abstracts:

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 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.

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作者: 孙妍珺 [1] 徐杨 [1] 吴德沛 [1] 沈宏杰 [1] 杨贞 [1] 仇惠英 [1] 陈苏宁 [1] 孙爱宁 [1]
期刊: 《中华血液学杂志》2015年36卷12期 1025-1030页 MEDLINEISTICPKUCSCD
栏目名称: 论著
DOI: 10.3760/cma.j.issn.0253-2727.2015.12.010
发布时间: 2016-01-12
基金项目:
国家自然科学基金 国家临床重点专科建设项目 卫生公益性行业科研专项 高等学校博士点新教师基金 江苏高校优势学科建设工程血液转化医学项目 江苏省科教兴卫工程-临床医学中心 江苏省科技厅生命健康专项
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