WT1基因指导的抢先治疗预防急性髓系白血病移植后复发的疗效及其最佳干预节点  

Efficacy of WT1 gene-guided pre-emptive therapy for prevention of relapse in acute myeloid leukemia after transplantation and its optimal intervention threshold

作　　者：方鹏[1,2,3,4] 高银 信红亚 柳林欣[1,2,3,4] 刘弋 徐雅靖[1,2,3,4] 陈焱 FANG Peng;GAO Yin;XIN Hongya;LIU Linxin;LIU Yi;XU Yajing;CHEN Yan(Department of Hematology,Xiangya Hospital,Central South University,Changsha 410008;National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Changsha 410008;Hunan Hematologic Neoplasms Clinical Medical Research Center,Changsha 410008;National Clinical Research Center for Hematologic Diseases,First Affiliated Hospital of Soochow University,Suzhou Jiangshu 215006;Department of Hematology,Affiliated Hospital of Yangzhou University,Yangzhou Jiangsu 225003,China)

机构地区：[1]中南大学湘雅医院血液科,长沙410008 [2]国家老年疾病临床医学研究中心(湘雅医院),长沙410008 [3]湖南省血液肿瘤临床医学研究中心,长沙410008 [4]国家血液系统疾病临床医学研究中心,苏州大学附属第一医院,江苏苏州215006 [5]扬州大学附属医院血液内科,江苏扬州225003

出　　处：《中南大学学报（医学版）》2024年第7期1120-1129,共10页Journal of Central South University ：Medical Science

基　　金：国家血液系统疾病临床研究中心转化研究课题(2021WWC02);中国抗癌协会-恒瑞TPO受体激动剂研究基金(CORP-253)。

摘　　要：目的:微量残留病(minimal residual disease,MRD)的监测与及时干预是预防成人急性髓系白血病(acute myeloid leukemia,AML)异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后复发的有效策略。泛白血病标志物WT1基因可作为AML患者MRD的监测指标。目前,临床上关于移植后基于WT1基因检测的抢先治疗的干预节点及干预时机尚无统一的标准。本研究旨在评估WT1基因指导的抢先治疗的临床价值,并进一步探讨其最佳干预节点。方法:回顾性收集2014年1月至2020年6月间在中南大学湘雅医院血液科接受alloHSCT的细胞遗传学风险为中危和高危成人AML患者的资料,所有患者均有移植后3年内的WT1基因表达检测数据。比较移植后接受抢先治疗的WT1基因阳性患者、未接受抢先治疗的WT1基因阳性患者之间,以及二者分别与移植后WT1基因阴性患者间终点指标[累积复发率(cumulative incidence of relapse,CIR)、无病生存(disease-free survival,DFS)率、总生存(overall survival,OS)率、非复发死亡(non-relapse mortality,NRM)率]的差异。纳入移植后未行干预的患者的数据,对可能影响预后的因素进行分析。将患者的年龄、性别、移植类型、细胞遗传学危险分层、移植前疾病状态、移植前WT1基因表达情况、移植后WT1基因表达情况、供者性别纳入单因素分析;进一步对单因素分析中P<0.10的因素纳入Cox回归模型进行多因素分析。采用受试者操作特征(receiver operating characteristic,ROC)曲线分析WT1基因表达水平预测复发的最佳截断值。结果:共纳入165例AML患者,86例在移植后3年内出现WT1基因阳性,其中58例接受抢先治疗,28例未接受抢先治疗。与移植后WT1基因阴性患者相比,未接受抢先治疗的WT1基因阳性患者的5年CIR明显升高(42.9%vs 10.5%,P<0.001)、5年DFS率(50.0%vs 80.7%,P=0.001)与OS率(60.7%vs82.8%,P=0.018)明显降低,5年NRM率差异无统计Objective:Monitoring minimal residual disease(MRD)and timely intervention are effective strategies for preventing relapse after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in adult acute myeloid leukemia(AML).The WT1 gene,a pan-leukemia marker,can be used as an indicator for MRD monitoring in AML patients.Currently,there is no unified standard for the intervention timing or treatment threshold based on WT1 gene detection after transplantation.This study aims to evaluate the clinical value of WT1 gene-guided preemptive therapy and further explore its optimal intervention threshold.Methods:Data of adult AML patients with intermediate or high-risk cytogenetics who underwent allo-HSCT between January 2014 and June 2020 at the Department of Hematology,Xiangya Hospital,Central South University,were retrospectively collected.All patients had WT1 gene expression data within three years post-transplantation.We compared the outcomes of WT1-positive patients who received preemptive therapy with those who did not,and both groups with WT1-negative patients.The endpoints analyzed included cumulative incidence of relapse(CIR),disease-free survival(DFS)rate,overall survival(OS)rate,and non-relapse mortality(NRM)rate.Data of patients who did not receive any intervention were included to analyze factors that might influence prognosis.Univariate analysis was performed using factors such as age,gender,transplantation type,cytogenetic risk stratification,pre-transplant disease status,pre-and post-transplant WT1 levels,and donor gender;factors with P<0.10 in univariate analysis were further included in a Cox regression model for multivariate analysis.Receiver operating characteristic(ROC)curve analysis was used to determine the optimal cut-off value of WT1 gene expression for predicting relapse.Results:A total of 165 AML patients were included,of whom 86 had WT1 gene positivity within three years post-transplantation.Among these,58 received preemptive therapy and 28 did not.Compared with WT1-negative patients,those WT

关 键 词：急性髓系白血病 造血干细胞移植 微量残留病 WT1基因 抢先治疗 

分 类 号：R733.71[医药卫生—肿瘤]