Objective: To investigate the clinical characteristics and long-term prognostic factors of relapsed pediatric acute lymphoblastic leukemia (ALL). Methods: 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. Results: 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)% vs. (16±5)%, (28±8)%, χ2=35.91, P<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)% vs. (31±5)%, (29±12)%, χ2=9.14, P<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)% vs. (90±10)%, (54±8)%, χ2=32.88, P<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)% vs. (26±5)%, χ2=14.04, P<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)% vs. (27±5)%, χ2=15.18, P<0.05). Multivariate analysis identified very early/early relapse (HR=3.91, 95%CI 1.96-7.79; HR=4.15, 95%CI 1.99-8.67), bone marrow relapse including isolated bone marrow relapse and combined relapse (HR=6.50, 95%CI 2.58-16.34; HR=5.19, 95%CI 1.78-15.16), with ETV6::RUNX1 (HR=0.23, 95%CI 0.07-0.74) and HSCT after relapse (HR=0.24, 95%CI 0.14-0.43) as independent prognostic factors for OS (all P<0.05). Conclusions: 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.
目的： 探讨复发急性淋巴细胞白血病（ALL）患儿的临床特征及长期预后影响因素。 方法： 回顾性队列研究。分析中国医学科学院血液病医院2008年4月至2015年4月按照中国儿童白血病协作组（CCLG）-ALL 2008方案初治的217例ALL复发患儿的年龄、复发时间、复发部位、分子生物学特征等临床资料，对其中136例复发后接受治疗的患儿按照不同复发时间、复发部位等临床资料进行分组，采用Kaplan-Meier法进行单因素分析评估患儿总生存率（OS）及无事件生存率（EFS），采用Cox比例风险回归模型进行多因素分析评估生存率的独立影响因素。 结果： 217例复发ALL患儿初诊年龄为5（3，7）岁，男135例，女82例，复发时间为22（10，39）个月，136例复发后接受治疗的患儿随访时间为65（47，90）个月，5年OS、EFS分别为（37±4）%、（26±4）%，预期10年OS、EFS分别为（35±5）%、（20±4）%。单因素分析显示，晚期复发组（43例）5年OS优于极早期复发（54例）和早期复发组（39例）［（72±7）%比（16±5）%、（28±8）%，χ2=35.91，P<0.05］，单纯髓外复发组（20例）5年OS优于单纯骨髓复发（102例）和联合复发组（14例）［（69±11）%比（31±5）%、（29±12）%，χ2=9.14，P<0.05］，高危组（80例）5年OS低于标危（10例）及中危组（46例）［（20±5）%比（90±10）%、（54±8）%，χ2=32.88，P<0.05］。ETV6：：RUNX1是最常见的融合基因（13.2%，18/136），预期10年OS优于ETV6：：RUNX1融合基因阴性组（118例）［（83±9）%比（26±5）%，χ2=14.04，P<0.05］，复发后行造血干细胞移植（HSCT）治疗组（42例）5年OS优于未行HSCT组（94例）［（56±8）%比（27±5）%，χ2=15.18，P<0.05］。多因素分析显示，极早期或早期复发（HR=3.91，95%CI 1.96~7.79；HR=4.15，95%CI 1.99~8.67）、骨髓复发（包括单纯骨髓复发和联合复发，HR=6.50，95%CI 2.58~16.34；HR=5.19，95%CI 1.78~15.16）、伴有ETV6：：RUNX1融合基因（HR=0.23，95%CI 0.07~0.74）、复发后行HSCT治疗（HR=0.24，95%CI 0.14~0.43）是复发ALL患儿OS的独立影响因素（均P<0.05）。 结论： 儿童ALL复发以极早期复发、骨髓复发为主，预后差，ETV6：：RUNX1是最常见的分子生物学异常且预后相对较好，HSCT可以改善复发患儿预后，但总体生存率仍低。.