初发儿童急性B淋巴细胞白血病细胞遗传学特征及首次治疗反应危险因素分析  

Analysis of cytogenetic characteristics of primary childhood B-cell acute lymphoblastic leukemia and risk factors for first treatment response

作　　者：连珠兰 葛丹丹 王玥[1] 郭碧赟[1] Lian Zhulan;Ge Dandan;Wang Yue;Guo Biyun(Department of Pediatrics,the First Affiliated Hospital of Xiamen University,Pediatrics Key Laboratory of Xiamen,Institute of Pediatrics,School of Medicine,Xiamen University,Xiamen 361003,China)

机构地区：[1]厦门大学附属第一医院儿科、厦门市儿科重点实验室、厦门大学儿童医学研究所,厦门361003

出　　处：《白血病．淋巴瘤》2023年第5期274-278,共5页Journal of Leukemia & Lymphoma

基　　金：厦门市儿童危重症救治与分级诊疗体系建设项目(YDZX20193502000003)。

摘　　要：目的探讨初发儿童急性B淋巴细胞白血病(B-ALL)的细胞遗传学特征及首次治疗反应相关影响因素。方法回顾性收集2019年4月至2021年9月厦门大学附属第一医院收治的49例初发B-ALL患儿资料,获得患儿临床特征、细胞遗传学和分子生物学检查结果、治疗前后临床指标等数据。按照儿童ALL诊疗规范(2018版),进行基因分型和首次诱导化疗后临床危险度分层及化疗方案制订。分析B-ALL患儿不同基因分型与临床指标的关系,采用Spearman等级相关分析法分析临床危险度分层与各指标的相关性。结果49例患儿中位年龄3.0岁(四分位数间距:3.2岁),男性32例(65.3%),女性17例(34.7%),男女比1.88∶1。治疗前基因突变35例(71.4%),无突变14例(28.6%)。基因突变35例中,E2A-PBX15例(10.2%),其中伴费城染色体(Ph)样1例;IKZF1缺失8例(16.3%),其中伴Ph样4例,伴Ph阳性1例,伴MLL重排1例;MLL重排3例(6.1%);单独Ph样12例(24.5%);TEL-AML16例(12.2%),其中伴Ph样2例;单独Ph阳性1例(2.0%)。临床危险度分层高危7例(14.3%),中危28例(57.1%),低危14例(28.6%)。诱导化疗前基因突变患者临床危险度高、中危患者比例[20.0%(7/35)比0.0%(0/14)、62.9%(22/35)比42.9%(6/14)]及诱导化疗第33天基因突变情况发生改变患者比例[42.9%(15/35)比0.0%(0/14)]均高于治疗前基因未突变患者(均P<0.01),诱导化疗前是否基因突变与性别、初诊时白细胞计数、激素敏感性、诱导化疗第15天至第19天骨髓微小残留病(MRD)、诱导化疗第33天MRD均不相关(均P>0.05)。患儿临床危险度分层与初诊时白细胞计数(r=0.392,P=0.005)、中性粒细胞计数(r=0.453,P=0.001)、淋巴细胞计数(r=0.418,P=0.001)、单核细胞计数(r=0.359,P=0.017)、血尿酸水平(r=0.378,P=0.007)、治疗前(r=0.316,P=0.027)和诱导化疗第15天至第19天(r=0.399,P=0.005)及诱导化疗第33天骨髓幼稚淋巴细胞比例(r=0.408,P=0.028)以及诱导化疗第33天骨髓MRD≥0.0001患儿比例(χ^(2)Objective To investigate the cytogenetic characteristics and influencing factors associated with first treatment response in primary childhood B-cell acute lymphoblastic leukemia(B-ALL).Methods The data of 49 children with primary B-ALL who were admitted to the First Hospital of Xiamen University from April 2019 to September 2021 were retrospectively collected,and the clinical characteristics,cytogenetic and molecular biology findings and other clinical indicators before and after treatment were obtained.Genotyping,clinical risk stratification after the first induction chemotherapy and chemotherapy regimen development were performed according to the pediatric ALL treatment specification(2018 version).The relationship between different genotypes and clinical indicators in children with B-ALL was analyzed,and the correlation between clinical risk stratification and each indicator was analyzed by Spearman rank correlation analysis.Results The median age of 49 children was 3.0 years old(interquartile range:3.2 years old),32 cases(65.3%)were male and 17 cases(34.7%)were female,with a male-to-female ratio of 1.88∶1.Thirty-five cases(71.4%)had gene mutations before treatment and 14 cases(28.6%)had no mutations.Among the 35 cases with mutations,E2A-PBX1 was found in 5 cases(10.2%),including 1 case with Philadelphia chromosome(Ph)-like;IKZF1 deletion was found in 8 cases(16.3%),including 4 cases with Ph-like,1 case with Ph-positive,and 1 case with MLL rearrangement;MLL rearrangement was found in 3 cases(6.1%);Ph-like alone was found in 12 cases(24.5%);TEL-AML1 was found in 6 cases(12.2%),including 2 cases with Ph-like;1 case(2.0%)with Ph-positive alone.The clinical risk stratification showed that 7 cases(14.3%)had high risk,28 cases(57.1%)had intermediate risk,and 14 cases(28.6%)had low risk.The proportions of patients with high and intermediate clinical risk before induction chemotherapy[20.0%(7/35)vs.0.0%(0/14),62.9%(22/35)vs.42.9%(6/14)]and the proportion of patients with altered mutation status on day 33 of inductio

关 键 词：白血病 B细胞 儿童 细胞遗传学分析 预后 

分 类 号：R733.71[医药卫生—肿瘤]