摘要
目的:探讨维奈克拉(VEN)联合阿扎胞苷(AZA)治疗FLT3-ITD突变复发难治急性髓系白血病(FLT3-ITD^(mut)R/R AML)的疗效,并分析患者的分子遗传学特征。方法:收集2018年11月至2021年4月期间深圳市第二人民医院血液科采用VEN联合AZA治疗的16例R/R AML患者的临床基线资料及随访数据,使用NGS或PCR方法检测患者突变基因,分析FLT3-ITD^(mut)AML患者的疗效及患者的分子遗传学特征。结果:FLT3-ITD^(mut)组CR/CRi患者占14.3%(1/7),FLT3-ITDwt组CR/CRi患者占22.2%(2/9),无显著性差异(P=0.69);FLT3-ITD^(mut)患者ORR(CR/CRi+PR)为42.9%(3/7),野生型患者ORR为44.4%(4/9),无显著性差异(P=0.95)。FLT3-ITD^(mut)患者中位生存期较野生型患者明显缩短,分别为130 d和300 d(P=0.02)。1例获得CR的FLT3-ITD^(mut)R/R AML患者合并IDH1突变;1例获得PR的FLT3-ITD^(mut)R/R AML患者合并SF3B1突变;3例合并NPM1突变的FLT3-ITD^(mut)R/R AML患者均未获得治疗反应。结论:VEN联合AZA方案对FLT3-ITD^(mut)R/R AML患者有一定疗效,但OS较短,需桥接移植。合并IDH1、SF3B1突变可能预示FLT3-ITD^(mut)R/R AML患者对治疗有反应,合并NPM1突变可能预示治疗反应不佳。
Objective:To explore the efficacy of venetoclax(VEN)plus azacitidine(AZA)in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia(FLT3-ITD^(mut)R/R AML)and analyze the molecular genetic characteristics of the patients.Methods:Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected.Leukemia related genes were detected by next-generation sequencing(NGS)or PCR.The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITD^(mut)R/R AML were analyzed.Results:14.3%(1/7)of the patients in FLT3-ITD^(mut)group and 22.2%(2/9)of the patients in FLT3-ITDwt group achieved complete remission(CR)/CR with incomplete blood count recovery(CRi),respectively,with no significant difference(P=0.69).There was no significant difference in overall response rate(ORR)(CR/CRi+PR)between FLT3-ITD^(mut)group and FLT3-ITDwt group[42.9%(3/7)vs 44.4%(4/9),P=0.95],too.The median overall survival(OS)time of FLT3-ITD^(mut)patients was significantly shorter than that of FLT3-ITDwt patients(130 vs 300 days,respectively)(P=0.02).Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR.Coexisting mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR.Three FLT3-ITD^(mut)R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA.Conclusion:VEN plus AZA showed a certain effect on patients with FLT3-ITD^(mut)R/R AML.To improve OS of the patients,bridging transplantation is need.IDH1 and SF3B1 mutations might predict that patients with FLT3-ITD^(mut)R/R AML have treatment response to VEN plus AZA,while the combination of NPM1 mutation may indicate poor response.
作者
翁光样
游伟文
刘焕勋
蔡云
杜新
WENG Guang-Yang;YOU Wei-Wen;LIU Huan-Xun;CAI Yun;DU Xin(Department of Hematology,Shenzhen Second People's Hospital,Shenzhen 518000,Guangdong Province,China)
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2023年第5期1333-1339,共7页
Journal of Experimental Hematology
