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[儿童复发性急性淋巴细胞白血病的临床特征及长期预后分析]

[Clinical features and long-term prognostic analysis of relapsed pediatric acute lymphoblastic leukemia].

作者信息

Wang N, Qi B Q, Ruan M, Zhang X Y, Zhang R R, Liu T F, Chen Y M, Zou Y, Guo Y, Yang W Y, Zhang L, Zhu X F, Chen X J

机构信息

Department of Pediatric Hematology and Oncology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Institutes of Health Science, Tianjin 300020, China.

出版信息

Zhonghua Er Ke Za Zhi. 2024 Nov 2;62(11):1090-1096. doi: 10.3760/cma.j.cn112140-20240914-00643.

Abstract

To investigate the clinical characteristics and long-term prognostic factors of relapsed pediatric acute lymphoblastic leukemia (ALL). Clinical data including the age, time from initial diagnosis to relapse, relapse site, and molecular biological features of 217 relapsed ALL children primarily treated by the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between April 2008 and April 2015 were collected and analyzed in this retrospective cohort study. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. The age at initial diagnosis of 217 relapsed patients was 5 (3, 7) years. There were 135 males and 82 females. The time from initial diagnosis to relapse of 217 children was 22 (10, 39) months. After relapse, 136 out of 217 children (62.7%) received treatment and the follow-up time was 65 (47, 90) months. The 5-year OS rate and EFS rate of the 136 relapsed children were (37±4) % and (26±4) %, respectively. The predicted 10-year OS rate and EFS rate were (35±5) % and (20±4) %, respectively. Univariate analysis showed that the 5-year OS rate in the group of patients with late relapse (43 cases) was significantly higher than those with very early (54 cases) and early relapse (39 cases) ((72±7)% (16±5)%, (28±8)%, =35.91, <0.05), 5-year OS rate of the isolated extramedullary relapse group (20 cases) was significantly higher than isolated bone marrow relapse group (102 cases) and combined relapse group (14 cases) ((69±11)% (31±5)%, (29±12)%, =9.14, <0.05), 5-year OS rate of high-risk group (80 cases) was significantly lower than standard-risk group (10 cases) and intermediate-risk group (46 cases) ((20±5)% (90±10)%, (54±8)%, =32.88, <0.05). ETV6::RUNX1 was the most common fusion gene (13.2%, 18/136). The predicted 10-year OS rate of relapsed children with positive ETV6::RUNX1 was significantly higher than those without ETV6::RUNX1 (118 cases) ((83±9)% (26±5)%, =14.04, <0.05). The 5-year OS for those accepted hematopoietic stem cell transplantation (HSCT) after relapse (42 cases) was higher than those without HSCT (94 cases) ((56±8)% (27±5)%, =15.18, <0.05). Multivariate analysis identified very early/early relapse (=3.91, 95% 1.96-7.79; =4.15, 95% 1.99-8.67), bone marrow relapse including isolated bone marrow relapse and combined relapse (=6.50, 95% 2.58-16.34; =5.19, 95% 1.78-15.16), with ETV6::RUNX1 (=0.23, 95% 0.07-0.74) and HSCT after relapse (=0.24, 95% 0.14-0.43) as independent prognostic factors for OS (all <0.05). Relapsed pediatric ALL mainly occurs very early and often affects bone marrow, which confer poor outcome. ETV6::RUNX1 is the most common genetic aberration with a favorable outcome. HSCT could rescue the outcome of relapsed children, though the survival rate is still poor.

摘要

探讨儿童急性淋巴细胞白血病(ALL)复发后的临床特征及长期预后因素。收集2008年4月至2015年4月在中国医学科学院血液病医院按照中国儿童白血病协作组(CCLG)-ALL 2008方案初次治疗后复发的217例ALL患儿的临床资料,包括年龄、从初次诊断至复发的时间、复发部位及分子生物学特征等,并进行回顾性队列研究分析。采用Kaplan-Meier分析评估总生存(OS)率和无事件生存(EFS)率进行单因素分析,采用Cox比例风险回归模型评估OS率和EFS率的影响因素进行多因素分析。217例复发患者初次诊断时的年龄为5(3,7)岁,男135例,女82例。217例患儿从初次诊断至复发的时间为22(10,39)个月。复发后,217例患儿中有136例(62.7%)接受治疗,随访时间为65(47,90)个月。136例复发患儿的5年OS率和EFS率分别为(37±4)%和(26±4)%,预测的10年OS率和EFS率分别为(35±5)%和(20±4)%。单因素分析显示,晚期复发组(43例)患者的5年OS率显著高于极早期复发组(54例)和早期复发组(39例)((72±7)% (16±5)%,(28±8)%,=35.91,<0.05),孤立髓外复发组(20例)的5年OS率显著高于孤立骨髓复发组(102例)和联合复发组(14例)((69±11)% (31±5)%,(29±12)%,=9.14,<0.05),高危组(80例)的5年OS率显著低于标危组(10例)和中危组(46例)((20±5)% (90±10)%,(54±8)%,=32.88,<0.05)。ETV6::RUNX1是最常见的融合基因(13.2%,18/136)。ETV6::RUNX1阳性的复发患儿预测的10年OS率显著高于ETV6::RUNX1阴性患儿(118例)((83±9)% (26±5)%,=14.04,<0.05)。复发后接受造血干细胞移植(HSCT)的患儿(42例)5年OS率高于未接受HSCT的患儿(94例)((56±8)% (27±5)%,=15.18,<0.05)。多因素分析确定极早期/早期复发(=3.91,95% 1.96 - 7.79;=4.15,95% 1.99 - 8.67)、骨髓复发包括孤立骨髓复发和联合复发(=6.50,95% 2.58 - 16.34;=5.19,95% 1.78 - 15.16)、ETV6::RUNX1阳性(=0.23,95% 0.07 - 0.74)和复发后HSCT(=0.24,95% 0.14 - 0.43)为OS的独立预后因素(均<0.05)。复发的儿童ALL主要发生在极早期,常累及骨髓,预后较差。ETV6::RUNX1是最常见的基因异常,预后较好。HSCT可改善复发患儿的预后,尽管生存率仍较低。

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