中国循证儿科杂志 ›› 2018, Vol. 13 ›› Issue (2): 107-112.

• 论著 • 上一篇    下一篇

RUNX1-RUNX1T1阳性儿童急性髓细胞白血病融合转录本动态监测的临床意义

陆继冉,高超,赵晓曦,李君,侯贝,李静,张瑞东,郑胡镛   

  1. 国家儿童医学中心,首都医科大学附属北京儿童医院血液肿瘤中心,儿童血液病与肿瘤分子分型北京市重点实验室,儿科学国家重点学科,儿科重大疾病研究教育部重点实验室 北京,100045
  • 收稿日期:2018-01-29 修回日期:2018-04-25 出版日期:2018-04-25 发布日期:2018-04-25
  • 通讯作者: 郑胡镛,高超
  • 基金资助:
     

Clinical significance of monitoring the transcript dynamics in RUNX1-RUNX1T1-positive pediatric acute myeloid leukemia

 LU Ji-ran, GAO Chao, ZHAO Xiao-xi, LI Jun, HOU Bei, LI Jing, ZHANG Rui-dong, ZHENG Hu-yong   

  1.  Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China
  • Received:2018-01-29 Revised:2018-04-25 Online:2018-04-25 Published:2018-04-25
  • Contact: ZHENG Hu-yong,GAO Chao
  • Supported by:
     

摘要: 目的:探讨 RUNX1-RUNX1T1+急性髓细胞白血病(AML) RUNX1-RUNX1T1转录本(融合转录本)的动态变化及其对预后的指导作用。 方法:回顾性队列研究,纳入2006年10月1日至2015年3月31日在首都医科大学附属北京儿童医院(我院)采用BCH-AML 05方案治疗的全部 RUNX1-RUNX1T1+ AML患儿,根据初诊(time point 0,TP0)、诱导Ⅰ后(TP1)、诱导Ⅱ后(TP2)、巩固Ⅰ后(TP3)、巩固Ⅱ后(TP4)和巩固Ⅲ后(TP5)融合转录本的检测情况,相应地分为高表达组和低表达组,分组界值分别为每104 GUS中融合转录本拷贝数104、103、102、10、1和0,随访至2017年12月31日。采用χ2检验比较初诊高表达组和低表达组临床和生物学特征的差异;Kaplan-Meier法分析患儿5年总生存(OS)和无复发生存(RFS),通过Log-rank检验比较组间差异,以Cox比例风险回归模型分析影响患儿5年OS和RFS的独立预后因素。 结果:符合本文纳入标准的患儿52例,男27例,中位年龄8(2~14)岁;2例TP1时失访,21例在随访中死亡,其余29例中位随访时间62.2(34.0~134.3)个月。①初诊高表达组(17/50)和低表达组(33/50)患儿的年龄、性别、WBC、Hb、PLT计数和骨髓幼稚细胞数、除CD15(P=0.004)外的免疫学表型、TP1~TP5的MRD差异均无统计学意义。②单因素分析表明,TP1和TP5融合转录本水平与患儿的5年OS和RFS相关,性别、初诊PLT与5年OS相关,初诊WBC与5年RFS相关。多因素分析显示,TP1时融合转录本水平>103拷贝/104 GUS是5年OS的独立不良因素(HR=0.095,95%:CI:0.011~0.860,P=0.036)。 结论: RUNX1-RUNX1T1+ AML患儿第1次诱导治疗结束后融合转录本水平是患儿长期预后的独立影响因素。

 

Abstract: Objective:To investigate the RUNX1-RUNX1T1 transcript (fusion transcript) dynamics in pediatric acute myeloid leukemia (AML) and their correlation with patients' clinico-biological characteristics and long-term outcomes. Methods:In a retrospective cohort, all patients with RUNX1-RUNX1T1-positive AML at Beijing Children's Hospital (our hospital), from October 1st, 2006 to March 31st, 2015 were enrolled. Patients were divided into high-expression or low-expression groups according to >104 copies, >103 copies, >102 copies, >10 copies, >1 copy and >0 copy per 104 copies GUS at diagnosis (time point 0, TP0) and following MRD detective time points, after Induction Ⅰ(TP1), Induction Ⅱ (TP2), and after ConsolidationⅠ (TP3), Consolidation Ⅱ (TP4) and Consolidation Ⅲ (TP5), respectively. The follow-up deadline was December 31st, 2017. Chi-square were used to test the differences of clinical and biological characteristics between the subgroups, Kaplan-Meier method was used to analyse patients' overall survival (OS) and relapse free survival (RFS), and Log-rank test for comparing the difference. Cox's proportional hazards regression model was used to analyze the independent significance for OS and RFS. Results:52 patients were enrolled and 27 of them were male, the median age was 8(2~14). Two patients were lost to follow up at TP1. 21 patients died during the follow-up, the median follow-up time of other 29 patients were 62.2(34~134.3) months. ①There were no significant differences in age, gender, WBC, Hb, PLT count, blasts account in the bone marrow, immunophenotype except CD15(P=0.004) and MRD of TP1~TP5 between the high-expression patients(17/50) and low-expression patients(33/50). ②Univariate analysis showed that RUNX1-RUNX1T1 transcript at TP1 and TP5 were corelated with 5 year OS and RFS, the gender and PLT count at TP0 were corelated with 5 year OS and WBC count at TP0 were corelated with 5 year RFS. Multivariate analysis showed that the RUNX1-RUNX1T1 transcript level >103 copies per 104 GUS at TP1 was the independent risk factor for poor OS of RUNX1-RUNX1T1+ pediatric AML patients, P=0.036, hazard ratio (HR) was 0.095 and the 95% confidence interval(CI) was (0.011, 0.860). Conclusion:The fusion transcript level after the first induction therapy was the independent factor affecting long outcome in RUNX1-RUNX1T1+ pediatric AML.

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