【作者】 刘恒；

【导师】 李子坚；

【作者基本信息】 兰州大学 ， 临床医学·内科学（专业学位）， 2024， 硕士

【摘要】 目的:分析急性髓系白血病微小残留病早期转阴的相关因素,以期为AML临床诊疗和精准分层提供更多的信息。方法:回顾性分析2018年1月至2023年12月兰州大学第一医院血液科收治的159例AML患者的临床资料,并分析急性髓系白血病微小残留病早期转阴的相关因素。根据MRD转阴时间分组,MRD早期转阴（首次诱导后）的患者78例,MRD早期未转阴的患者81例。本研究以多参数流式细胞术检测MRD,MRD<10^-4定义为MRD阴性。结果:1.159例患者中携带基因突变的患者有152例,半数以上的患者携带3种及以上的基因突变。其中,携带1种、2种、3种、4种、5种、6种、7种、8种基因突变的患者分别为27例、36例、29例、26例、17例、13例、2例、1例,最多的携带12种基因突变,可见于1例患者。FLT3-ITD和TET2突变是发生频率最高的基因突变,可见于41例患者,其次是DNMT3A、ASXL1、NPM1突变,分别可见于38例、36例、33例的患者,WT1、NRAS、IDH2、CEBPA b ZIP、TP53、^*CEBPA突变分别可见于31例、27例、22例、19例、19例、17例的患者,其余RUNX1、KIT、FLT3-TKD等基因突变频率均不足10%。2.单因素COX回归分析显示MRD早期未转阴、年龄≥60岁、MPO不表达、IDH2野生型是患者OS的不良预后因素。多因素COX回归分析显示MRD早期未转阴、年龄≥60岁、不伴IDH2突变是不良结局的独立危险因素,MRD早期转阴、年龄<60岁、IDH2突变的患者的OS更好。KM生存分析显示MRD早期转阴、年龄<60岁、IDH2突变的患者具有更高的总生存率。3.单因素分析显示,MPO表达水平、WT1突变、NPM1突变、TET2突变与MRD早期转阴具有相关性。多因素分析显示,MPO表达水平、WT1突变、NPM1突变、TET2突变是MRD早期转阴的独立相关因素,其中MPO表达、WT1突变、NPM1突变是MRD早期转阴的促进因素,TET2突变是MRD早期转阴的不利因素。4.利用四个独立相关因素构建了AML患者MRD早期转阴的预测模型。ROC曲线和AUC值表明,该列线图有较好的区分能力;校准曲线和DCA曲线表明,该模型具有较好的准确度和临床实用性。结论:1.MRD早期转阴是OS的独立保护因素,MRD早期转阴的患者具有更高的总生存率。MPO表达、WT1突变、NPM1突变、TET2突变是MRD早期转阴的独立的相关因素,且MPO表达、WT1突变、NPM1突变是MRD早期转阴的促进因素,TET2突变是MRD早期转阴的不利因素。2.利用MRD早期转阴的四个独立相关因素构建了预测AML患者MRD早期转阴的列线图。该列线图可对AML患者MRD早期转阴概率进行有效和客观的评估。更多还原

【Abstract】 Objective:This study aims to analyze the associated factors of early negative conversion of minimal residual disease in acute myeloid leukemia.The findings will provide valuable information for the clinical diagnosis and treatment of AML,as well as precise stratification.Methods:The study retrospectively analyzed the clinical data of 159 AML patients admitted to the Department of Hematology of the First Hospital of Lanzhou University from January 2018 to December 2023.The analysis focused on the relevant factors of the early negative conversion of MRD in acute myeloid leukemia.The study grouped patients based on the timing of MRD negative conversion.There were 78 patients with early MRD negative conversion（after first induction）,and 81 patients with early MRD non-negative conversion.MRD was detected using multiparametric flow cytometry,and MRD<10^-4 was defined as MRD negative.Results:1.152 out of 159 patients carried gene mutations,more than half of the patients had more than three gene mutations.Among them,27 patients carried only one gene mutation,while 36 patients,29 patients,26 patients,17 patients,13 patients,2 patients,and 1 patient had two,three,four,five,six,seven,and eight gene mutations,respectively.The highest number of gene mutations were 12,carried by 1 patient.FLT3-ITD and TET2 mutations were the most frequent gene mutations,observed in 41patients.This was followed by DNMT3A,ASXL1,and NPM1 mutations,which were observed in 38 patients,36 patients,and 33 patients,respectively.Additionally,gene mutations in WT1,NRAS,IDH2,CEBPA b ZIP,TP53,and^*CEBPA were observed in31 patients,27 patients,22 patients,19 patients,19 patients,17 patients,respectively.Gene mutations frequency in RUNX1,KIT,and FLT3-TKD were present in less than10%of the patients.2.The results of the one-way COX regression analysis indicate that MRD early non-negative conversion,age≥60 years,MPO non-expression,and IDH2 wild type were identified as poor prognostic factors for OS in patients.Multifactorial COX regression analysis showed that MRD early non-negative conversion,age≥60 years,and without IDH2 mutation were significant predictors of OS.Independent risk factors for poor outcome were identified as age≥60 years,absence of early MRD negative conversion,and lack of IDH2 mutation.Patients with early MRD conversion,age<60years,and IDH2 mutation have a better OS.The KM survival analysis revealed that patients with early MRD negative conversion had a higher overall survival.Additionally,patients who were age<60 years and had an IDH2 mutation also had higher overall survival.3.The results of the univariate analysis indicate that MPO expression level,WT1mutation,NPM1 mutation,and TET2 mutation were significantly correlated with MRD early negative conversion.The multifactorial analysis revealed that MPO expression level,WT1 mutation,NPM1 mutation and TET2 mutation were independent correlation factors of MRD early negative conversion.Specifically,MPO expression,WT1mutation,and NPM1 mutation were found to facilitate MRD early negative conversion,while TET2 mutation was identified as unfavorable for MRD early negative conversion.4.A prediction model was constructed to predict MRD early negative conversion in AML patients using four independent correlation factors of MRD early negative conversion.The ROC curve and AUC value demonstrated the good discriminatory ability of the column plot.The calibration curve and DCA curve indicated that the model had good accuracy and clinical utility.Conclusions:1.MRD early negative conversion is an independent protective factor for OS,and patients with MRD early negative conversion have a higher overall survival rate.MPO expression,WT1 mutation,NPM1 mutation,TET2 mutation are independent correlation factors of early MRD negative conversion;MPO expression,WT1 mutation,NPM1 mutation are facilitators and TET2 mutation are impediments of early MRD negative conversion.2.A column chart was created to predict early MRD negative conversion in AML patients using four independent correlation factors of MRD early negative conversion.更多还原