Cui Lei, Zhang Rui-Dong, Gao Chao, Li Wei-Jing, Zhao Xiao-Xi, Zheng Hu-Yong, Li Zhi-Gang, Wu Min-Yuan
Hematology Oncology Center, Beijing Key Laboratory of Pediatric Hematology and Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education; National Key Discipline of Pediatrics; Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.
Hematology Oncology Center, Beijing Key Laboratory of Pediatric Hematology and Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education; National Key Discipline of Pediatrics; Beijing Children's Hospital, Capital Medical University, Beijing 100045, China. E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Apr;22(2):298-303. doi: 10.7534/j.issn.1009-2137.2014.02.007.
This study was purposed to investigate the prognostic value of early response to treatment in childhood acute lymphoblastic leukemia (ALL). Four indexes were used to assess early response to treatment including response to prednisone on day 8 (D8-PR), percentage of lymphoblast in bone marrow on day 22 (D22-BM) and day 33 (D33-BM), the level of minimal residual disease (MRD) on day 33 (D33-MRD) by morphological and molecular biological method in 426 children with ALL. Prognostic impact of early response to treatment was analyzed, and multivariate analysis of the predictive value was performed by Cox-regression analysis. All patients were followed up until October 31, 2013, with a median follow-up time of 80 months (0.5 to 106 months). The results showed that there were significant differences between event free survivals (EFS) of the sub-groups divided according to the four indexes. The 8 years-EFS in patients with prednisone good response (PGR) was significantly higher than that in patients with prednisone poor response (PPR);patients with M1 in bone marrow on day 22 or day 33 had the better outcomes than that of patients with M2/M3;patients with high level of MRD ( ≥ 10(-4)) had the worse outcomes as compared with patients with low level of MRD (<10(-4)) (P < 0.001). Cox proportional hazard model analysis showed that BCR/ABL fusion gene positive, D8-PR, D33-BM and D33-MRD were the independent prognostic factors for childhood ALL, and the hazard ratio of D33-MRD ≥ 10(-2) was highest (HR:11.886, P < 0.001). It is concluded that early response to treatment is an independent prognostic factor with important prognostic values, and it has important clinical guiding instructive significance for risk stratification in the treatment of children ALL.
本研究旨在探讨儿童急性淋巴细胞白血病（ALL）早期治疗反应的预后价值。采用4项指标评估426例ALL患儿的早期治疗反应，包括第8天泼尼松反应（D8-PR）、第22天（D22-BM）和第33天（D33-BM）骨髓原始淋巴细胞百分比，以及第33天采用形态学和分子生物学方法检测的微小残留病（MRD）水平（D33-MRD）。分析早期治疗反应的预后影响，并通过Cox回归分析对预测价值进行多因素分析。所有患者随访至2013年10月31日，中位随访时间为80个月（0.5至106个月）。结果显示，根据这4项指标划分的亚组无事件生存率（EFS）之间存在显著差异。泼尼松反应良好（PGR）患者的8年EFS显著高于泼尼松反应不良（PPR）患者；第22天或第33天骨髓M1型患者的预后优于M2/M3型患者；MRD水平高（≥10⁻⁴）的患者与MRD水平低（<10⁻⁴）的患者相比预后更差（P<0.001）。Cox比例风险模型分析显示，BCR/ABL融合基因阳性、D8-PR、D33-BM和D33-MRD是儿童ALL的独立预后因素，D33-MRD≥10⁻²的风险比最高（HR：11.886，P<0.001）。结论：早期治疗反应是具有重要预后价值的独立预后因素，对儿童ALL治疗中的危险度分层具有重要的临床指导意义。
