CCLG-ALL 2008方案治疗143例儿童ALL的MRD监测临床意义分析

Clinical significance of MRD monitoring in 143 childhood ALL treated with CCLG-ALL-2008 procotol

目的对143例儿童急性淋巴细胞白血病(ALL)治疗的长期随访结果进行分析,探讨微小残留病(MRD)监测对儿童ALL的无事件生存率(EFS)及复发的影响。方法回顾性分析2013年1月1日—2015年10月31日我院接受CCLG-ALL2008方案治疗的143例ALL患儿,采集骨髓样品使用流式细胞学检测化疗第15d,第33d及第12周MRD表达水平并调整分度,采用Kaplan-Meier方法评估EFS,用Log-rank法进行组间比较,采用COX回归分析影响预后的因素,以P <0. 05为差异具有显著性。结果根据MRD调整分度后标危组42例(29. 4%)、中危组74例(51.7%)、高危组27例(18.9%),5年EFS率分别为77.3%、67.3%、56.3%,采用Log-rank法进行组间比较,第15d MRD≥10^(-3)、第33d MRD≥10^(-4)、第12周MRD≥10^(-3),最终分度和BCR-ABL(+)组间EFS差异具有显著性(P<0.05),经过多因素COX回归分析,结果显示,监测第33d MRD≥10^(-4)、最终危险分度、BCR-ABL(+)为影响EFS的危险因素(P<0.05)。随访至2018年1月1日,共有29例复发(20. 3%),标危组、中危组、高危组复发率分别是6. 9%、44. 8%、48. 3%(P <0. 05)。结论监测第33d MRD是ALL治疗方案重要的分层参数,对进行危险度分级,判断复发发生,具有重要的临床指导意义。

Objective To analyze the long-term follow-up prognosis of childhood acute lymphoblastic leukemia(ALL)In 143 patients,explore the efficacy of minimal residual disease(MRD)monitoring prediction on event-free survival(EFS).Methods From January 1 st 2013 to October 31 st2015,143 patients diagnosed with ALL and treated with the CCLG-ALL 2008 protocol were employed in this study.Bone marrow MRD was measured by flow cytometry on 15th day,33rd day and 12th week of induction chemotherapy.Adjusting the risk stratification according to MRD levels.The Kaplan-Meier method was used to estimate the EFS rate,differences were compared with the Log-rank method,and the COX regression analysis was used to evaluate the prognosis.Results Based the MRD levels,42 patients(29.4%)were in the standard-risk group,74 patients(51.7%)in the middle-risk group,and 27 patients(18.9%)in the high-risk group.The 5-year EFS rates at standard-risk,middle-risk,high-risk group were 77.3%,67.3%,and 56.3%,respectively.According to Log-rank method,the MRD10-3 on the 15th day,the MRD>10-4on the 33rd day,the MRD≥10-3 on the 12th week,and BCR-ABL(+)were associated with poor prognosis(P<0.05).MRD≥10-4 on the 33rd,and BCR-ABL(+)were independent prognostic factors by multivariate analysis(P<0.05).29(20.3%)patients developed relapse until January 1 st,2018.The relapse rate in the standard-risk,middle-risk and the high-risk groups were 6.9%、44.8%and 48.3%,respectively(P<0.05).Conclusions The MRD≥10-4 on the 33rd is an independent prognostic factor for childhood ALL.It has great clinical significance to conduct risk classification and judge the recurrence.