儿童急性淋巴细胞白血病早期治疗反应评估与预后价值  

Evaluation of Early Response to Treatment and Its Prognostic Value in Childhood Acute Lymphoblastic Leukemia

作　　者：崔蕾[1] 张瑞东[1] 高超[1] 李伟京[1] 赵晓曦[1] 郑胡镛[1] 李志刚[1] 吴敏媛[1] 

机构地区：[1]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、教育部儿科重大疾病重点实验、儿科学国家重点学科,北京100045

出　　处：《中国实验血液学杂志》2014年第2期298-303,共6页Journal of Experimental Hematology

基　　金：国家自然科学基金项目(81200392);国家自然科学基金项目(81170504);北京市教育委员会科技计划重点项目(KZ201210025031);国家科技支撑计划项目(2007BAI04B03)

摘　　要：本研究目的是探讨儿童急性淋巴细胞白血病(ALL)早期治疗反应在儿童ALL预后中的价值。采用细胞形态学和分子生物学(定量PCR)方法对2005年3月31日至2008年3月31日期间我院收治的426例初治ALL患儿进行了早期治疗反应评估,评估内容包括第8天强的松试验反应(D8-PR)、第22天骨髓缓解状态(D22-BM)、第33天骨髓缓解状态(D33-BM),以及第33天MRD水平(D33-MRD)。单因素分析4个评估指标对无事件生存率(EFS)的影响,Cox比例风险模型分析其独立预后意义。所有病例随访截止至2013年10月31日,中位随访时间80个月(0.5-106个月)。结果表明:单因素分析4个早期治疗反应评估指标均具有明显的预后意义。强的松反应良好(PGR)患儿的8年EFS明显高于强的松反应不良(PPR)患儿;第22天、第33天骨髓缓解状态为M1骨髓的患儿预后明显好于M2、M3骨髓的患儿;第33天MRD高水平(≥10-4)的患儿预后明显差于MRD低水平(<10-4)患儿(P<0.001)。多因素分析结果显示,儿童ALL中具有独立预后意义的指标有BCR/ABL+、D8-PR、D33-BM和D33-MRD,其中以D33-MRD≥10-2的风险比最高(HR:11.886,P<0.001)。结论:早期治疗反应在儿童ALL中具有重要的预后价值,是具有独立意义的预后因素,对儿童ALL的危险度分层治疗中具有重要的临床指导意义。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 thatof 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 I〉 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.

关 键 词：急性淋巴细胞白血病 早期治疗反应 微小残留病 预后价值 

分 类 号：R733.71[医药卫生—肿瘤]