儿童急性B淋巴细胞性白血病诱导缓解治疗期白血病细胞清除率指标检测研究  

Clinical research on clearance of leukemic cell during induction of remission therapy in children with precursor B cell acute lymphoblastic leukemia

作　　者：易志刚[1] 崔蕾[2] 高超[2] 金眉[2] 张瑞东[2] 李志刚[2] 吴敏媛[2] 

机构地区：[1]川北医学院附属医院儿科,637000 [2]首都医科大学附属北京儿童医院血液病中心,100045

出　　处：《中华儿科杂志》2011年第3期170-174,共5页Chinese Journal of Pediatrics

基　　金：国家科技支撑计划课题资助项日（2007BAI04B03）;北京市科技计划基金资助项目（D0905001040431）;北京市科技新星计划基金资助项目（2005B06）

摘　　要：目的 探讨儿童急性B淋巴细胞性白血病（BCP-ALL）诱导缓解治疗期白血病细胞清除率（CL）对于预测复发的临床价值.方法 对206例初治BCP-ALL患儿进行3方面研究：（1）分析诱导缓解治疗期CL对无复发生存率（RFS）的影响.CL的3类4项评估指标包括：第8天泼尼松敏感试验（d8-PR）、诱导缓解治疗第22天、第33天骨髓形态学检测（d22-BM、d33-BM）、第33天微小残留病检测（d33-MRD）;（2）计算4个评估指标预测复发的灵敏度、特异度、阳性预测值及阴性预测值,评价各指标预测复发的效力;（3）分析4个指标的一致性.结果 （1）单因素生存分析中,分别按4个指标将患儿分成不同的亚组,各亚组的RFS差异均有统计学意义（P＜0.01）;Cox比例风险模型分析显示d33-MRD≥10-3、BCR/ABL融合基因阳性具有独立预后意义.（2）d33-MRD预测复发灵敏度最高（69.9%）,而特异度（88.5%）最低.（3）3类指标之间的一致性差,但d22-BM、d33-BM呈幼稚细胞≥5%的病例全部呈d33-MRD≥10-3,而d8-PR呈泼尼松反应不良的病例则不然,表明d8-PR含有d33-MRD所不能涵括的预后信息.结论 诱导缓解治疗期白血病细胞清除率对儿童BCP-ALL具有重要临床价值;诱导缓解治疗后骨髓MRD检测预测复发的灵敏度显著高于形态学检测,而泼尼松敏感试验结合诱导缓解治疗后骨髓MRD检测可能是评估白血病细胞清除率的最好方法.Objective To investigate the clinical value of clearance of leukemic cell during induction of remission therapy in children with precursor B cell acute lymphoblastic leukemia （ BCP-ALL）,and to assess the applicative value of different indexes. Method From April 2005 to April 2008, 206children with de novo BCP-ALL were admitted. We firstly analyzed the effect of clearance of leukemic cells during induction of remission therapy on relapse-free survival （RFS）. Four indexes were used to assess the clearance of leukemic cells including prednisone response on day 8 （ d8-PR ）, percentage of lymphoblast in bone marrow on day 22 （ d22-BM ） and day 33 （ d33-BM ） , and bone marrow （ BM ） minimal residualdisease （MRD） detection on day 33 （d33-MRD）. Then the sensitivity, specificity, positive predictive value and negative predictive value of the four indexes to assess their ability to predict relapse were analyzed.Finally, the consistency between two of the four indexes to explore the relationships among them were analyzed. Result There were significant differences between RFS of the sub-groups divided according tod8-PR, d22-BM, d33-BM, d33-MRD （ P ＜ 0. 01 ）; Cox proportional hazard model analysis showed that d33-MRD≥ 10-3 and positive BCR/ABL fusion gene were the independent prognostic factors. Sensitivity ofd33-MRD was higher than that of morphology detection （ d22-BM, d33-BM and d8-PR） in prediction of relapse, and positive predictive value of morphology detection was higher than that of d33-MRD. Sensitivity could be greatly increased by combination with clinical and biological characteristics. Consistency could not be found between d8-PR and d22-BM, d33-BM, d33-MRD, as well as between d22-BM, d33-BM, and d33-MRD. However, all cases of d22-BM, d33-BM M2/M3 were d33-MRD ≥ 10-3, while the same phenomenon could not be found for patients with poor d8-PR. Conclusion Clearance of leukemic cell during induction of remission therapy in children with BCP-ALL had important clinical value

关 键 词：白血病 B细胞 急性 代谢清除率 缓解诱导 肿瘤 残余 分子生物学 

分 类 号：R733.71[医药卫生—肿瘤]