TKI药物联合化疗治疗伴C-KIT突变的急性髓系白血病-M2b患者疗效及安全性分析

Clinical efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy in treatment of acute myelogenous leukemia-M2b with C-KIT mutation

目的:探讨TKI药物联合化疗治疗伴C-KIT突变的AML-M2b患者的疗效及安全性。方法:2016年2月至2019年6月在郑州大学附属肿瘤医院住院的10例伴C-KIT突变的AML-M2b患者,男5例,女5例,年龄为14~59岁,其中包括多周期化疗后复发1例;多周期化疗后不缓解2例;化疗1周期后不缓解3例;多周期化疗后融合基因不转阴2例;融合基因转阴后再次转阳2例。分别给予TKI药物(首选伊马替尼患者2例,首选达沙替尼患者8例)联合化疗方案再次诱导缓解治疗,评估其疗效及监测不良反应。结果:10例患者中8号外显子突变2例(2/10,20%),17号外显子突变8例(8/10,80%);联合治疗后2例无效,总有效率80%(8/10),期间均未出现肝肾功能损害及胸腔积液的发生。10例患者中2例无效患者均行异基因造血干细胞移植术,1例移植过程中死亡,1例移植后3月复发,余8例患者TKI药物应用后的生存期为4月+~30月+。结论:AML-M2b患者中C-KIT突变位点主要为激酶功能域的D816突变;联合TKI药物治疗能明显提高伴C-KIT突变患者的疗效。

Objective:To analyze the efficacy and safety of tyrosine kinase inhibitors(TKI)combined with chemotherapy in treatment of acute myelogenous leukemia-M2b(AML-M2b)with C-KIT mutation.Methods:Ten patients of AML-M2b with C-KIT mutation were in hospital from February 2016 to June 2019,aged from 14~59 years old including 5 cases of males and 5 cases of females.Ten patients were including 1 patient who relapsed after many cycles of chemotherapy,2 patients who did not remission after many cycles of chemotherapy,3 patients who did not remission after one cycle of chemotherapy,2 patients whose fusion gene was not negative after many cycles of chemotherapy,2 patients whose fusion gene turned to be positive after many cycles of chemotherapy.Then 10 patients who were treated with tyrosine kinase inhibitors(2 patinets with imatinib,8 patients with dasatinib)combined with chemotherapy respectively were reinduced,and we would evaluate the efficacy and monitor the adverse reaction.Results:There were 2 patients(2/10,20%)whose mutation site of C-KIT was in exon 8,8 patients(8/10,80%)in exon 17.Two patients were in vain after combination therapy,and the total effective rate was 80%.There were no liver and kidney dysfunction and pleural effusion during the whole time of treatment.Two patients accepted allo-HSCT,one of them died in the allo-HSCT,the other one relapsed three months later.The over survival of the remaining 8 patients after TKI treatment was 4 months+~30 months+.Conclusion:The main mutation site of C-KIT in AML-M2b was D816 mutation,Adding TKI to treatment in AML-M2b with C-KIT mutation could improve the outcome obviously.