二代测序技术检测儿童急性B淋巴细胞白血病IGH/IGK基因克隆性重排微小残留病的临床意义  

Clinical significance of next-generation sequencing-based IGH/IGK gene rearrangement analysis in the diagnosis of minimal residual disease of children with acute B-cell lymphoblastic leukemia

作　　者：李慧敏[1] 康美云 薛瑶 王娅萍 张姮 戎留成 黄婕[1] 方拥军[1] Li Huimin;Kang Meiyun;Xue Yao;Wang Yaping;Zhang Heng;Rong Liucheng;Huang Jie;Fang Yongjun(Department of Hematology and Oncology,Children′s Hospital of Nanjing Medical University,Nanjing 210008,China)

机构地区：[1]南京医科大学附属儿童医院血液肿瘤科,南京210008

出　　处：《中华实用儿科临床杂志》2023年第5期348-351,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(81903383);江苏省卫生健康委医学科研立项项目(ZDB2020018);南京市卫生科技发展专项基金(JQX19008)。

摘　　要：目的与流式细胞术(FCM)比较,评价基于IGH/IGK基因克隆性重排的二代测序技术(NGS)在检测儿童急性B淋巴细胞白血病(B-ALL)微小残留病(MRD)中的临床意义。方法回顾性分析南京医科大学附属儿童医院2019年7月至2021年7月诊断的85例B-ALL患儿的临床信息、初诊及诱导治疗后骨髓NGS-MRD与FCM-MRD结果,采用χ^(2)检验或Fisher′s精确概率法比较2种方法的灵敏性和阳性率,并采用Spearman相关分析比较两者的相关性。结果初诊时患儿通过NGS方法均检测到优势克隆序列,75例(88.2%)通过FCM方法找到筛选标记。诱导治疗后,同一时间点NGS-MRD与FCM-MRD阳性率分别为31.8%(27/85)和9.4%(8/85),差异有统计学意义(P<0.001)。与FCM相比,NGS方法具有良好的灵敏度(100.0%)、特异度(75.3%)及阴性预测值(100.0%),阳性预测值为29.6%。NGS-MRD定量结果与FCM-MRD具有良好的相关性(r=0.569,P<0.001)。截至2022年7月27日,2例NGS-MRD(+)FCM-MRD(-)患儿在维持治疗期间出现复发。结论NGS与FCM用于检测B-ALL患儿MRD具有较高一致性。与FCM相比,NGS在灵敏性方面具有显著优势。将NGS与FCM两种方式相结合用于监测B-ALL患儿诱导治疗后骨髓MRD,能让他们更大程度获益。Objective To assess the clinical significance of next-generation sequencing(NGS)-based IGH/IGK gene rearrangement analysis versus flow cytometry(FCM)in diagnosing minimal residual disease(MRD)of children with acute B-cell lymphoblastic leukemia(B-ALL).Methods Clinical data,NGS-MRD and FCM-MRD findings at the initial diagnosis and after induction chemotherapy of 85 children diagnosed as B-ALL in Children′s Hospital of Nanjing Medical University from July 2019 to July 2021,were retrospectively analyzed.The sensitivity of the two methods,and the positive rate were compared byχ^(2) test or Fisher′s test.The correlation was identified by Spearman correlation analysis.Results Dominant clone sequences were detected in all children at the initial diagnosis by NGS,while selection markers were identified by FCM in 75(88.2%)patients.Positive MRD rate detected by NGS-MRD was significantly higher than that of FCM-MRD at the same time point after induction chemotherapy[31.8%(27/85)vs.9.4%(8/85),P<0.001].Compared with those of FCM-MRD,NGS-MRD had good sensitivity(100.0%),specificity(75.3%)and negative predictive value(100.0%),and the positive predictive value was 29.6%.MRD results detected by NGS were consistent with that of FCM(r=0.569,P<0.001).By July 27,2022,2 patients with NGS-MRD(+)FCM-MRD(-)relapsed during maintenance chemotherapy.Conclusions NGS is highly consistent with FCM in the detection of MRD in children with B-ALL,which is more sensitive.The combination of NGS-MRD and FCM-MRD benefits more in monitoring MRD in children with B-ALL after induction chemotherapy.

关 键 词：二代测序 急性淋巴细胞白血病 微小残留病 流式细胞术 

分 类 号：R733.71[医药卫生—肿瘤]