MLL基因重排阳性的儿童急性白血病患者的临床特点及预后分析  

Clinical characteristics and prognosis of pediatric acute leukemia patients with MLL gene rearrangements

作　　者：刘青[1] 张娜[1] 邵静波[1] 李红[1] 陈凯[1] 杜成坎 王真 蒋慧[1] LIU Qing;ZHANG Na;SHAO Jing-bo;LI Hong;CHEN Kai;DU Cheng-kan;WANG Zhen;JIANG Hui(Department of Hematology and Oncology,Shanghai Children's Hospital,Shanghai Jiao Tong University,Shanghai 200040,China;Department of Clinical Laboratory,Shanghai Children's Hospital,Shanghai Jiao Tong University,Shanghai 200040,China)

机构地区：[1]上海交通大学附属儿童医院/上海市儿童医院血液肿瘤科,上海200040 [2]上海交通大学附属儿童医院/上海市儿童医院检验科,上海200040

出　　处：《上海交通大学学报（医学版）》2021年第7期903-909,共7页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市卫生健康委员会科研课题基金(20194Y0112);上海申康医院发展中心重大临床研究项目(SHDC2020CR4089)。

摘　　要：目的·分析混合谱系白血病(mixed linage leukemia,MLL)基因重排(MLL rearrangement,MLL-r)阳性的儿童急性白血病(acute leukemia,AL)患者的临床特点及预后情况。方法·回顾性分析2009年1月1日至2019年12月31日上海交通大学附属儿童医院收治的MLL-r AL患儿45例。采用荧光原位杂交和/或实时荧光定量PCR检测MLL-r。Kaplan-Meier法评估患儿生存情况,Log-rank检验比较各组生存率。对性别、年龄、白细胞数等影响生存的指标进行单因素和多因素分析。结果·AL患儿MLL-r的检出率为7.1%;在急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)和急性髓细胞性白血病(acute myeloid leukemia,AML)中MLL-r的检出率分别为5.4%和13.3%,二者差异有统计学意义(P=0.002);2组患儿的年龄(>1岁和≤1岁)和初发时白细胞数(≥50×10^(9)/L和<50×10^(9)/L)比较,差异均有统计学意义(P=0.032和P=0.021)。MLL-r ALL患儿的免疫分型以早期前体B-ALL为主,占79.2%;MLL-r AML患儿以M5为主,占77.8%。MLL伙伴基因分析,ALL患儿MLL/AF4占59.2%(16/27),其中小于1岁的患儿占68.7%(11/16),与非MLL/AF4组小于1岁的患儿数相比差异有统计学意义(P=0.034);AML患儿以MLL/AF9为主,占33.3%。42例患儿可进行疗效分析,完全缓解率为97.6%(41/42),中位随访时间26个月(2~138个月),中位无事件生存(event-free survival,EFS)和总生存(overall survival,OS)时间分别为21个月和24.5个月,3年EFS和OS率分别为(41.8±9.4)%和(60.9±9.3)%。MLL-r ALL患儿中位EFS和OS时间分别为21.5个月和28个月,3年EFS和OS率分别为(44.3±11.7)%和(58.2±12.1)%。MLL-r AML患儿中位EFS和OS时间分别为16个月和23个月,2年EFS和OS率分别为(36.5±15.8)%和(64.7±14.5)%。ALL患儿复发8例,中位复发时间20个月(2~36个月);AML患儿复发7例,中位复发时间16个月(5~38个月);二者累积复发率分别为48.4%和63.9%,差异无统计学意义(P=0.398)。单因素分析显示,MLL-r ALL患儿年龄>1岁与≤1岁组、白细胞数�Objective·To analyze the clinical characteristics and prognosis of pediatric acute leukemia(AL)patients with positive mixed linage leukemia(MLL)gene rearrangement(MLL-r).Methods·Forty-five children with MLL-r AL admitted to Shanghai Children′s Hospital,Shanghai Jiao Tong University from January 1,2009 to December 31,2019 were retrospectively analyzed.Fluorescence in situ hybridization and/or fluorescent real-time PCR were used to detect the MLL-r.Kaplan-Meier method was used to evaluate the survival of children.Log-rank test was used to compare the difference of survival rate.Univariate analysis and multivariate analysis were performed on the factors influencing survival,such as gender,age and the number of white blood cells.Results·The incidence rate of MLL-r in children with AL in our center was 7.1%,and the incidence rate of MLL-r in children with acute lymphoblastic leukemia(ALL)and acute myeloid leukemia(AML)were 5.4%and 13.3%,respectively.The difference between the two groups was statistically significant(P=0.002).The age of the two groups of children(>1 year and≤1 year)and the number of white blood cells at the time of onset(≥50×10^(9)/L and<50×10^(9)/L)were compared.The differences were statistically significant(P=0.032 and 0.021).The main immunophenotype of children with MLL-r ALL was early precursor B-ALL,accounting for 79.2%.The main immunophenotype of children with MLL-r AML was M5,accounting for 77.8%.MLL partner gene analysis showed that MLL/AF4 accounted for 59.2%(16/27)of MLL-r ALL children,of which 68.7%(11/16)were children younger than 1 year old.Compared with the children younger than 1 year old in the non-MLL/AF4 group,the difference was statistically significant(P=0.034).The majority of children with MLL-r AML were MLL/AF9,accounting for 33.3%.Of the 45 patients,42 cases were included for the prognosis analysis.The complete remission rate was 97.6%(41/42),and the median follow-up time was 26(2‒138)months.The median event-free survival(EFS)and overall survival(OS)time were 21 mont

关 键 词：白血病 混合谱系白血病基因 儿童 预后分析 

分 类 号：R733.71[医药卫生—肿瘤]