动态监测FLT3-ITD基因突变在急性髓系白血病中的意义

Significance of Dynamic Monitoring of FLT3-ITD Mutation in Acute Myeloid Leukemia

目的:分析急性髓系白血病(AML)化疗前后FLT3-ITD基因突变与临床缓解的相关性,探讨FLT3-ITD基因动态改变对评估AML患者临床疗效的意义。方法:分析2016年6月—2019年6月中山市人民医院收治的初诊AML患者178例(除M3型),通过PCR扩增联合一代测序的方法检测骨髓单个核细胞FLT3-ITD突变情况,比较FLT3-ITD阳性患者与阴性患者临床特征和缓解率的差异。结果:AML初诊患者中FLT3-ITD阳性患者(33例)的中位白细胞计数、骨髓原始细胞比例及血乳酸脱氢酶水平明显高于FLT3-ITD阴性患者(145例)(P<0.05);AML初诊FLT3-ITD阳性患者与阴性患者相比,具有更低的完全缓解率(42.4%vs58.6%,P<0.05);而在FLT3-ITD初诊阳性患者(33例)中,化疗后持续阳性患者(5例)的完全缓解率显著低于化疗后阴性的患者(28例)(0.0%vs 50.0%,P<0.05)。结论:AML初诊FLT3-ITD阳性患者化疗效果欠佳,化疗后FLT3-ITD持续阳性与AML难以缓解相关,提示连续监测FLT3-ITD突变有助于判断治疗效果、评估疾病预后。

Objective:therapy in acute myeloid leukemia(AML),and to explore the significance of FLT3-ITD gene dynamic changes in evaluating theclinical efficacy of AML patients.Methods:The clinical data of 178 patients(except M3 type)with initial diagnosis of AML fromJune 2016 to June 2019 were analyzed,and the FLT3-ITD mutations of bone marrow mononuclear cells were detected by PCR am-plification combined with first-generation sequencing.The clinical features and remission rates of FLT3-ITD positive patients andFLT3-ITD negative patients were compared.Results:The median white blood cell count,bone marrow blast ratio and blood lactatedehydrogenase levels in FLT3-ITD positive patients(33 cases)were significantly higher than FLT3-ITD negative patients(145 cas-es)(P<0.05).Compared with negative patients,AML newly diagnosed FLT3-ITD positive patients had a lower complete remissionrate(42.4%vs 58.6%,P<0.05).Among newly diagnosed FLT3-ITD positive patients(33 cases),the complete remission rate of pa-tients who continued to be positive after chemotherapy(5 cases)was significantly lower than that of patients who were negative af-ter chemotherapy(28 cases)(0%vs 50%,P<0.05).Conclusion:AML patients with FLT3-ITD-positive patients who were newlydiagnosed had poor chemotherapy effects.The continued positive FLT3-ITD after chemotherapy was associated with difficulty in re-lieving AML,suggesting that continuous monitoring of FLT3-ITD mutations can help to judge the therapeutic effect and assess dis-ease prognosis..