流式细胞术检测微小残留病对儿童急性B淋巴细胞白血病预后判断的临床价值

Clinical value of minimal residual disease detection by flow cytometry in childhood B-cell acute lymphoblastic leukemia

摘要:

目的 探讨4色荧光标记B淋巴细胞抗体组合模板用于流式细胞术检测微小残留病(MRD)对儿童急性B淋巴细胞白血病(B-ALL)预后判断的临床价值.方法 回顾性分析2010年10月至2012年3月间采用流式细胞技术检测MRD的初发B-ALL患儿的相关临床资料.根据MRD检测的时间及检测的结果,将183例患儿分为诱导缓解期MRD阴性组(n=37),诱导缓解期MRD阳性组(n=18),维持治疗期MRD阴性组(n=113)和维持治疗期MRD阳性组(n=15).结果 诱导缓解期和维持治疗期MRD阳性患儿,其初诊危险分级为中、高危的患者比例较阴性者高(P<0.05).维持治疗期MRD阳性组患儿的3年累积复发率明显高于阴性组(P=0.04).Cox分析显示对强的松不敏感(RR=1.005,95%CI:0.864~1.170,P=0.032)、第15天骨髓象未达M1(RR=6.454,95%CI:2.191~19.01,P=0.002)和缓解后MRD≥0.01%(RR=1.923,95%CI:0.750~4.933,P=0.043)是儿童B-ALL发生复发的高危因素.结论 4色荧光标记B淋巴细胞抗体组合模板用于流式细胞术能区分化疗后MRD阳性和阴性的B-ALL患儿.MRD水平与强的松反应性、第15天骨髓象等指标一样,是儿童B-ALL重要的预后判断因素,对儿童B-ALL具有较好的临床预后判断意义.

Abstract:

Objective To elevate the prognostic value of minimal residual disease (MRD) detection by four-color flow cytometry with the antibody panel in childhood B-cell acute lymphoblastic leukemia (B-ALL). Methods The clinical data of 183 children with newly-diagnosed acute B-ALL and who accepted MRD detection between October 2010 and March 2012 was retrospectively reviewed. According to the detection time and result of MRD, the 183 children were classified into four groups: MRD negative (n=37) and positive (n=18) in the induction chemotherapy and MRD negative (n=113) and positive (n=15) in the maintenance chemotherapy. Results During both induction and maintenance chemotherapy, the percentage of patients at high and median risk in the MRD positive group was higher than in the MRD positive group (P<0.05). In the maintenance chemotherapy group, the 3-year cumulative incidence of relapse in MRD positive patients was higher than negative patients (P=0.04). The Cox's proportional hazards regression analysis showed that insensitive reaction for prednisone (RR=1.005, 95%CI: 0.864-1.170, P=0.032), bone marrow morphology that did not meet M1 on the 15th day (RR=6.454, 95%CI: 2.191-19.01, P=0.002) and MRD≥0.01% (RR=1.923, 95%CI: 0.750-4.933, P=0.043) were risk factors for relapse in children with B-ALL. Conclusions The four-color flow cytometry with the antibody panel can distinguish from MRD positive patients from negative patients with B-ALL. The result of MRD detection, as prednisone sensitivity and bone marrow morphology on the 15th day, is also a independent prognostic factor in children with B-ALL.