微小残留病在TCF3/PBX1^(+)的儿童急性B淋巴细胞白血病中的临床意义

Clinical Significance of Minimal Residual Disease in Pediatric Patients with TCF3/PBX1+B-cell Acute Lymphoblastic Leukemia

目的:探讨流式细胞术(FCM)和聚合酶链反应(PCR)技术在TCF3/PBX1^(+)的儿童急性B淋巴细胞白血病(B-ALL)不同治疗阶段进行微小残留病(MRD)检测的一致性及检测结果与预后的相关性。方法:回顾性分析2005年1月至2017年12月北京大学人民医院儿科收治的64例TCF3/PBX1^(+)B-ALL患儿的临床资料,分别采用FCM和PCR方法在治疗d33和d90对64例患儿的同期骨髓标本进行MRD检测,并对检测结果进行分析。结果:64例患儿中男37例,女27例,中位年龄8(0.8-16.0)岁,完全缓解(CR)率为100%,其中1疗程CR率为98.4%(62/63);随访期内共12例患儿出现复发,中位复发时间16.9(5.3-46.3)个月,总体中位随访时间77.2(1.0-184.8)个月,5年总生存(OS)率和无事件生存(EFS)率分别为82.8%±4.7%和75.0%±5.4%。化疗3个月时(d90),2种方法检测MRD结果的一致率为98.4%,相关Kappa值为0.792(P<0.001),一致性明显高于诱导化疗后(d33)的一致率(76.7%)及相关Kappa值(0.328);诱导化疗后(d33),MRD-FCM-组的5年EFS率(79.3%±5.3%)明显优于MRD-FCM+组(40.0%±21.9%)(P=0.028);MRD-PCR+组和MRD-PCR-组的5年OS率及EFS率的差异无统计学意义;MRD-FCM-/PCR-组的5年EFS率(85.4%±5.5%)明显优于MRD-FCM+/PCR+组(40.0%±21.9%)(P=0.026)。结论:在儿童TCF3/PBX1~+B-ALL中,采用FCM和PCR方法检测的MRD结果具有较好的一致性,尤其是巩固化疗期(d90)的一致性更高。诱导化疗后(d33)的MRD水平是影响长期预后的重要因素,特别是应用FCM方法于d33进行的MRD检测结果与预后明显相关。

Objective:To explore the consistency of flow cytometry(FCM)method and polymerase chain reaction(PCR)technique in the detection of minimal residual disease(MRD)at different treatment stages in pediatric patients with TCF3/PBX1+B-cell acute lymphoblastic leukemia(B-ALL)and the correlations between the detection results and prognosis.Methods:The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1+B-ALL admitted to the Department of Pediatrics of Peking University People′s Hospital from January 2005 to December 2017 were retrospectively analyzed.FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively,and the detection results were analyzed.Results:There were 37 males and 27 females in the 64 patients,with a median age of 8 years(range 0.8 to 16 years).The complete remission(CR)rate after the first cycle of induction chemotherapy was 98.4%(62/63),with overall CR rate of 100%.12 patients experienced recurrence,with a median recurrence time of 16.9(5.3-46.3)months.The median followup time of the 64 patients was 77.2(1.0-184.8)months,and the 5-year overall survival(OS)rate and event-free survival(EFS)rate were 82.8%±4.7%and 75.0%±5.4%,respectively.On d90,the concordance rate of the MRD results from the two methods was 98.4%,and the related kappa value was 0.792(P<0.001),which were significantly higher than those on d33.After induction chemotherapy(d33),the 5-year EFS rate of MRD-FCM-group(79.3%±5.3%)was significantly better than that of MRD-F CM^(+)group(40.0%±21.9%)(P=0.028),there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR+group and MRD-PCR-group,and the 5-year EFS rate of MRD-FCM-/PCR-group(85.4%±5.5%)was significantly better than that of MRD-FCM^(+)/PCR+group(40.0%±21.9%)(P=0.026).Conclusion:In children with TCF3/PBX1+B-ALL,the MRD results detected by FCM and PCR methods show good consistency,especially in consolidation therapy period(d90).The MRD level at the end of induction therapy(d33)is an important factor affecting the long-term prognosis,especially the MRD results detected by FCM method,which is significantly associated with prognosis.