Liu F, Chen X J, Guo Y, Yang W Y, Chen X, Zhang X Y, Zhang R R, Ren Y Y, Zhu X F
State Key Laboratory of Experimental Hematology; National Clinical Research Center for Blood Diseases; Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2020 Nov 14;41(11):896-902. doi: 10.3760/cma.j.issn.0253-2727.2020.11.003.
To evaluate the predictive role of ETV6-RUNX1 fusion gene in protocol CCLG-ALL-2008 as well as identify the prognostic factors that influence the outcome of ALL with ETV6-RUNX1 fusion gene. One hundred and seventy-eight patients newly diagnosed with pediatric acute lymphoblastic leukemia with ETV6-RUNX1 rearrangement from April 2008 to April 2015 were enrolled in CCLG-ALL-2008. The follow up period ended in July 2018; we performed retrospective analyses of their data to determine the efficacy of the regimen and the prognostic factors. The median age of the study population (178 pediatric patients) , including 100 boys and 78 girls was 4 (1-13) y, and the median white blood cell count at diagnosis was 9.46 (1.25-239.83) ×10(9)/L. Three patients died, and 1 was lost to follow up by the end of the first induction chemotherapy, resulting in an induced remission rate of 97.8% (174/178) . The cumulative incidence of relapse was 15.9% with a median follow up of 73.5 mon. Total 83.3% of the relapse cases were those of isolated bone marrow relapse, while 79.2% of the cases were those of late relapse. The median interval time between relapse and first complete remission was 35.5 mon (range, 1-62 months) . One of the 5 patients with early recurrence and 7 of the 19 with late recurrence cases survived. The 5-year-OS and 5-year-EFS of ETV6-RUNX1 positive children was (89.4±2.4) % and (82.1±6.9) %, respectively. The estimated 10-year-OS and 10-year-EFS of ETV6-RUNX1 positive children was (88.6±2.5) % and (77.3±4.0) %, respectively. The Kaplan-Meier method and Log-rank test were used to estimate and compare the survival. Univariate statistical analysis showed that poor prognostic factors that influenced survival included central nervous system state 2 at diagnosis, poor prednisone response, high risk, gene positivity after induction chemotherapy, as well as MRD positivity and gene positivity at the 12(th) week. In the multivariate analysis, only the central nervous system state 2 at diagnosis and MRD positivity at the 12(th) week were associated with the outcome. ETV6-RUNX1-positive ALL is a subgroup with a favorable prognosis as per the CCLG-ALL-2008 protocol. Patients with ETV6-RUNX1 should be given more intensive therapy, including hematopoietic stem cell transplantation when they are CNS2 at diagnosis or have high level of MRD at the 12(th) week after treatment.
评估ETV6-RUNX1融合基因在CCLG-ALL-2008方案中的预测作用，并确定影响伴有ETV6-RUNX1融合基因的急性淋巴细胞白血病（ALL）预后的因素。2008年4月至2015年4月新诊断为伴有ETV6-RUNX1重排的小儿急性淋巴细胞白血病的178例患者纳入CCLG-ALL-2008研究。随访期至2018年7月结束；我们对其数据进行回顾性分析以确定该方案的疗效及预后因素。研究人群（178例小儿患者）的中位年龄为4（1 - 13）岁，其中男孩100例，女孩78例，诊断时的中位白细胞计数为9.46（1.25 - 239.83）×10⁹/L。3例患者死亡，1例在首次诱导化疗结束时失访，诱导缓解率为97.8%（174/178）。中位随访73.5个月时，复发累积发生率为15.9%。83.3%的复发病例为单纯骨髓复发，79.2%的病例为晚期复发。复发与首次完全缓解之间的中位间隔时间为35.5个月（范围1 - 62个月）。5例早期复发患者中有1例存活，19例晚期复发患者中有7例存活。ETV6-RUNX1阳性儿童的5年总生存率（OS）和5年无事件生存率（EFS）分别为（89.4±2.4）%和（82.1±6.9）%。ETV6-RUNX1阳性儿童的估计10年OS和10年EFS分别为（88.6±2.5）%和（77.3±4.0）%。采用Kaplan-Meier法和Log-rank检验来估计和比较生存率。单因素统计分析显示，影响生存的不良预后因素包括诊断时中枢神经系统状态2、泼尼松反应差、高危、诱导化疗后基因阳性，以及第12周时微小残留病（MRD）阳性和基因阳性。多因素分析中，仅诊断时中枢神经系统状态2和第12周时MRD阳性与预后相关。根据CCLG-ALL-2008方案，ETV6-RUNX1阳性ALL是一个预后良好的亚组。对于诊断时为CNS2或治疗后第12周MRD水平高的ETV6-RUNX1阳性患者，应给予更强化的治疗，包括造血干细胞移植。
