诱导治疗早期微小残留病监测在儿童急性淋巴细胞白血病治疗中的多中心评价  

Multicenter evaluation of minimal residual disease monitoring in early induction therapy for treatment of childhood acute lymphoblastic leukemia

作　　者：吴晓君 廖宁[2] 麦惠容[3] 李欣瑜[1] 万伍卿[4] 杨丽华[5] 黄礼彬[6] 罗湘琴 田川 陈启文[9] 龙兴江[10] 何云燕[2] 王缨[3] 李志光[11] 徐宏贵[1] Wu Xiaojun;Liao Ning;Mai Huirong;Li Xinyu;Wan Wuqing;Yang Lihua;Huang Libin;Luo Xiangqin;Tian Chuan;Chen Qiwen;Long Xingjiang;He Yunyan;Wang Ying;Li Chi-Kong;Xu Honggui(Department of Hematology and Oncology,Children′s Medical Center,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China;Department of Pediatrics,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Department of Hematology and Oncology,Shenzhen Children′s Hospital,Shenzhen 518026,China;Department of Pediatrics,the Second Xiangya Hospital of Central South University,Changsha 410011,China;Department of Pediatric Hematology,Zhujiang Hospital,Southern Medical University,Guangzhou 510280,China;Department of Pediatrics,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510062,China;Department of Pediatrics,the Third Affiliated Hospital,Sun Yat-sen University,Guangzhou 510630,China;Department of Pediatrics,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524002,China;Department of Pediatrics,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Department of Pediatrics,Liuzhou People′s Hospital,Liuzhou 545006,China;Department of Pediatrics,Prince of Wales Hospital,Hong Kong 999077,China)

机构地区：[1]中山大学孙逸仙纪念医院儿童医学中心血液肿瘤科,广州510120 [2]广西医科大学第一附属医院儿科,南宁530021 [3]深圳市儿童医院血液肿瘤科,深圳518026 [4]中南大学湘雅二医院儿科,长沙410011 [5]南方医科大学珠江医院小儿血液科,广州510280 [6]中山大学附属第一医院儿科,广州510062 [7]中山大学附属第三医院儿科,广州510630 [8]广东医科大学附属医院儿科,湛江524002 [9]南昌大学第一附属医院儿科,南昌330006 [10]柳州市人民医院儿科,柳州545006 [11]香港中文大学威尔斯亲王医院儿科,中国香港999077

出　　处：《中华儿科杂志》2024年第4期337-344,共8页Chinese Journal of Pediatrics

基　　金：中山大学临床医学研究5010计划(2007016)。

摘　　要：目的探讨诱导治疗早期微小残留病(MRD)监测对儿童急性淋巴细胞白血病(ALL)治疗的价值。方法多中心回顾性队列研究。分析2016年10月至2019年6月华南儿童急性淋巴细胞白血病协作组的16家医院治疗的1164例初诊ALL患儿临床资料。根据诱导治疗第15天MRD水平分为MRD<0.10%组、MRD 0.10%~<10.00%组、MRD≥10.00%组;根据诱导治疗第33天MRD水平分为MRD<0.01%组、MRD 0.01%~<1.00%组、MRD≥1.00%组。分析各组间年龄、初诊白细胞计数、有无中枢神经系统白血病(CNSL)、分子遗传学特征等差异,应用Kaplan-Meier法进行生存分析,Cox回归模型进行预后相关因素分析。结果1164例ALL患儿中男692例、女472例,诊断年龄4.7(0.5,17.4)岁,初诊白细胞计数10.7(0.4,1409.0)×109/L,53例(4.6%)有CNSL,随访时间47.6(0.5,68.8)个月。5年总生存率(OS)为(93.1±0.8)%,无复发生存率(RFS)为(90.3±1.1)%。诱导治疗第15天MRD<0.10%组466例,MRD 0.10%~<10.00%组523例,MRD≥10.00%组175例,5年OS分别为(95.4±1.0)%、(93.3±1.1)%、(85.4±2.9)%,三组间比较差异有统计学意义(χ^(2)=16.47,P<0.05);5年RFS分别为(93.2±1.6)%、(90.8±1.4)%、(78.9±4.3)%,三组间比较差异有统计学意义(χ^(2)=21.06,P<0.05)。诱导治疗第33天MRD<0.01%组925例,MRD 0.01%~<1.00%组164例,MRD≥1.00%组59例,5年RFS分别为(91.4±1.2)%、(84.5±3.2)%、(87.9±5.1)%,三组间比较差异有统计学意义(χ^(2)=9.11,P=0.010)。诱导治疗第15天MRD≥10.00%的ALL患儿中,第33天MRD<0.01%组80例,第33天MRD 0.01%~<1.00%组45例,第33天MRD≥1.00%组45例,5年RFS分别为(83.9±6.0)%、(67.1±8.2)%、(83.3±6.9)%,三组间比较差异有统计学意义(χ^(2)=6.90,P=0.032)。对诱导治疗第15天MRD≥10.00%组、第33天MRD 0.01%~<1.00%组单因素分析显示,第15天MRD≥10.00%组伴有CNSL患儿5年RFS明显低于不伴CNSL患儿[(50.0±20.4)%比(80.3±4.4)%,χ^(2)=4.13,P=0.042]。第33天MRD 0.01%~<1.00%组伴有CNSL或MLL基因重排患儿5年RFS明显低于不伴CNSL或Objective To evaluate the role of minimal residual disease(MRD)monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia(ALL).Methods This was a multicenter retrospective cohort study.Clinical data of 1164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group.According to MRD assay on day 15 of early induction therapy,they were divided into MRD<0.10%group,MRD 0.10%-<10.00%group and MRD≥10.00%group.According to MRD assay on day 33,they were divided into MRD<0.01%group,MRD 0.01%-<1.00%group and MRD≥1.00%group.Age,onset white blood cell count,central nervous system leukemia(CNSL),molecular genetic characteristics and other data were compared between groups.Kaplan-Meier method was used for survival analysis.Cox regression model was used to analyze prognostic factors.Results Of the 1164 enrolled patients,there were 692 males and 472 females.The age of diagnosis was 4.7(0.5,17.4)years.The white blood cell count at initial diagnosis was 10.7(0.4,1409.0)×109/L.Among all patients,53 cases(4.6%)had CNSL.The follow-up time was 47.6(0.5,68.8)months.The 5-year overall survival(OS)and 5-year relapse-free survival(RFS)rates were(93.1±0.8)%and(90.3±1.1)%.On day 15 of early induction therapy,there were 466 cases in the MRD<0.10%group,523 cases in the MRD 0.10%-<10.00%group and 175 cases in the MRD≥10.00%group.The 5-year OS rates of the MRD<0.10%group,MRD 0.10%-<10.00%group and MRD≥10.00%group were(95.4±1.0)%,(93.3±1.1)%,(85.4±2.9)%,respectively,while the RFS rates were(93.2±1.6)%,(90.8±1.4)%,(78.9±4.3)%,respectively(χ^(2)=16.47,21.06,both P<0.05).On day 33 of early induction therapy,there were 925 cases in the MRD<0.01%group,164 cases in the MRD 0.01%-<1.00%group and 59 cases in the MRD≥1.00%group.The 5-year RFS rates in the MRD 0.01%-<1.00%group was lowest among three groups((91.4±1.2)%vs.(84.5±3.2)%vs.(87.9±5.1)%).The difference between three groups is statistically significant(

关 键 词：白血病 多中心研究 预后 儿童 

分 类 号：R733.71[医药卫生—肿瘤]