地西他滨联合半量CAG方案治疗≥70岁的初诊急性髓系白血病患者疗效观察  

Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged≥70 Years with Newly Diagnosed Acute Myeloid Leukemia

作　　者：曹蓝 江兆清 刘文洁 孙倩[1] 朱雨[1] 李建勇[1] 钱思轩[1] 洪鸣[1] CAO Lan;JIANG Zhao-Qing;LIU Wen-Jie;SUN Qian;ZHU Yu;LI Jian-Yong;QIAN Si-Xuan;HONG Ming(Department of Hematology,The First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,Jiangsu Province,China)

机构地区：[1]南京医科大学第一附属医院江苏省人民医院血液科,江苏南京210029

出　　处：《中国实验血液学杂志》2023年第3期633-642,共10页Journal of Experimental Hematology

摘　　要：目的:探讨地西他滨联合半量CAG(D-CAG)方案治疗≥70岁的初诊急性髓系白血病(AML)的临床疗效及安全性。方法:回顾性分析2010年11月至2021年6月在南京医科大学第一附属医院血液科初诊的59例≥70岁的老年AML患者的临床资料。结果:59例AML患者中,男性28例,女性31例,中位年龄74(70-86)岁。D-CAG方案诱导治疗2个疗程的完全缓解(CR)率为69.4%(34/49),中位CR持续时间为10.7(0.6-125.4)个月。依据英国医学研究理事会染色体核型标准分组,预后良好组仅有1例获得CR,预后中等组CR率为71.8%(28/39),预后不良组CR率为55.6%(5/9),预后中等及不良组CR率无显著性差异。参考AML(2017年)ELN预后分层标准,预后良好组CR率为88.2%(15/17),预后中等组CR率为45.5%(5/11),预后不良组CR率为66.7%(14/21),预后良好组与预后不良组的CR率无差异,但均高于预后中等组(P<0.05)。通过二代测序分析59例患者基因突变情况,结果显示发生频率在10%以上的基因突变有11种,分别为TET2突变(35.6%)、ASXL1突变(30.5%)、NPM1突变(28.8%)、FLT3-ITD突变(27.1%)、DNMT3A突变(22.0%)、IDH1突变(15.3%)、CEBPA单突变(13.6%)、TP53突变(13.6%)、IDH2突变(11.9%)、RUNX1突变(11.9%)、NRAS突变(10.2%),上述11种基因突变频率在CR与非CR组间差异无统计学意义。与正常染色体核型相比,复杂核型的患者更易出现TP53突变(P<0.001),而FLT3-ITD及DNMT3A突变则更容易出现在正常核型患者中(P=0.04,P=0.047)。所有患者中位随访时间为11.7(1.5-128.2)个月,中位总生存期(OS)为12.3(1.5-128.2)个月,中位无事件生存期(EFS)为8.5(1.5-128.2)个月。CR患者的中位OS及中位EFS分别为19.8个月和13.3个月,明显长于治疗失败者的6.4个月和5.7个月(P<0.001,P=0.009)。对于突变频率>10%的突变基因,通过卡方检验及生存分析与野生型患者进行对比,发现CR率、中位OS及中位EFS的差异均无统计学意义。单因素分析发现初诊时患者年龄、血红蛋白Objective:To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen(D-C AG regimen)in patients aged≥70 years with newly diagnosed acute myeloid leukemia(AML).Methods:The clinical data of 59 AML patients(≥70 years old)who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021were retrospectively analyzed.Results:Among the 59 AML patients,28 were males and 31 were females,with a median age of 74(70-86)years.The complete remission(CR)rate was 69.4%(34/49),and the median duration of CR was 10.7(0.6-125.4)months after 2 courses of D-C AG treatment.According to the British Medical Research Council(MRC)classification,there was only one patient in the favorable-risk group,and the CR rate was 71.8%(28/39)in the intermediate-risk group,and 55.6%(5/9)in the adverse-risk group,respectively.There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group.Referring to ELN 2017 genetic risk classification,CR rate was 88.2%(15/17)in the favorable-risk group,45.5%(5/11)in the intermediate-risk group,and 66.7%(14/21)in the adverse-risk group.There was no significant difference in CR rate between the favorable-risk and adverse-risk categories,but both were significantly higher than that in the intermediate-risk group(P<0.05).Next-generation sequencing(NGS)analysis showed that 11 gene mutations with a frequency of more than 10%,including TET2 mutation(35.6%),ASXL1 mutation(30.5%),NPM1 mutation(28.8%),FLT3-ITD mutation(27.1%),DNMT3A mutation(22.0%),IDH1 mutation(15.3%),CEBPA single mutation(13.6%),TP53mutation(13.6%),IDH2 mutation(11.9%),RUNX1 mutation(11.9%),and NRAS mutation(10.2%).There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group.Compared with normal karyotypes,patients with complex karyotypes were more likely to develop TP53 mutations(P<0.001),while FLT3-ITD and DNMT3A mutations were more li

关 键 词：急性髓系白血病 地西他滨 D-CAG方案 有效性 安全性 

分 类 号：R733.71[医药卫生—肿瘤]