伴TP53突变儿童急性淋巴细胞白血病的临床特征及预后分析  

Clinical characteristics and prognosis analysis of children with acute lymphoblastic leukemia and TP53 mutation

作　　者：郑湧智 乐少华[1] 李健[1] 陈再生[1] 华雪玲[1] 胡建达[2] 郑浩[1] Zheng Yongzhi;Le Shaohua;Li Jian;Chen Zaisheng;Hua Xueling;Hu Jianda;Zheng Hao(Department of Pediatric Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,China;Department of Hematology,Fujian Medical University Union Hospital,Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fuzhou 350001,China)

机构地区：[1]福建医科大学附属协和医院小儿血液科,福州350001 [2]福建医科大学附属协和医院血液科,福建省血液病研究所,福建省血液病学重点实验室,福州350001

出　　处：《白血病．淋巴瘤》2022年第6期343-347,共5页Journal of Leukemia & Lymphoma

基　　金：福建医科大学启航基金(2019QH1032);福建省血液医学中心建设项目(闽政办(2017)4号)。

摘　　要：目的探讨伴TP53突变儿童急性淋巴细胞白血病(ALL)的临床特征、疗效及TP53突变与儿童ALL预后的关系。方法收集2016年11月至2019年12月福建医科大学附属协和医院应用二代测序技术进行骨髓标本全外显子基因检测的141例初诊ALL患儿临床资料。回顾性分析TP53突变患儿临床特征,采用Kaplan-Meier法比较是否伴TP53突变患儿总生存(OS)和无事件生存(EFS)。结果141例初诊ALL患儿中5例(3.5%)检出TP53突变,均为急性前体B淋巴细胞白血病(B-ALL),急性T淋巴细胞白血病(T-ALL)患儿中未检出TP53突变,TP53突变者占B-ALL患儿的4.0%(5/126)。TP53突变类型均为单核苷酸变异。5例伴TP53突变的ALL患儿均为男性,中位年龄60个月(16~156个月);初诊时均贫血、乳酸脱氢酶升高,4例皮下出血及高尿酸血症;免疫表型均为前体B细胞型,4例伴有髓系抗原表达。接受规范治疗的4例伴TP53突变ALL患儿中,2例复发,复发时间分别为8.9个月和12.1个月。伴TP53突变ALL患儿的预计15个月EFS率和OS率均低于TP53未突变ALL患儿(37.5%比97.7%,χ^(2)=29.90,P<0.001;37.5%比98.3%,χ^(2)=24.90,P<0.001)。结论伴TP53突变ALL患儿以男性、B细胞型多见,早期复发率高,疗效差;TP53突变可能成为预后评估的必要补充。Objective To investigate the clinical characteristics and efficacy of children with acute lymphoblastic leukemia(ALL)and TP53 mutation,and to explore the relationship between TP53 mutation and the prognosis of children with ALL.Methods The clinical data of 141 children with newly diagnosed ALL from November 2016 to December 2019 in Fujian Medical University Union Hospital were collected,and the whole-exome gene assay was performed in bone marrow samples of the children by using next-generation sequencing technology.The clinical characteristics of children with TP53 mutation were retrospectively analyzed,and the Kaplan-Meier method was used to compare the overall survival(OS)and event-free survival(EFS)of children with or without TP53 mutation.Results Among the 141 children with newly diagnosed ALL,TP53 mutations were detected in 5 children(3.5%),all of which were B-precursor acute lymphoblastic leukemia(B-ALL).No TP53 mutation was detected in T-cell acute lymphoblastic leukemia(T-ALL)children,and TP53 mutation accounted for 4.0%(5/126)of B-ALL children.The types of TP53 mutation were all single nucleotide variants.Five ALL children with TP53 mutation were male,with a median age of 60 months(16-156 months).At the time of onset,all children had anemia and elevated lactate dehydrogenase,and 4 children had subcutaneous hemorrhage and hyperuricemia.The immunophenotypes of all children were precursor B-cell type,and 4 children had myeloid antigen expression.Among 4 ALL children with TP53 mutation who received standard treatment,2 cases relapsed,and the recurrence time was 8.9 months and 12.1 months,respectively.The expected 15-month EFS rate and OS rate of ALL children with TP53 mutation were lower than those of ALL children without TP53 mutation(37.5%vs.97.7%,χ^(2)=29.90,P<0.001;37.5%vs.98.3%,χ^(2)=24.90,P<0.001).Conclusions ALL children with TP53 mutation are more commonly found in male and B-cell type,with high early recurrence rate and poor efficacy.TP53 mutation may become a necessary supplement for prognostic a

关 键 词：白血病 淋巴细胞性 急性 TP53突变 二代测序 儿童 预后 

分 类 号：R733.71[医药卫生—肿瘤]