定期监测微小残留病变对儿童急性淋巴细胞白血病的预后价值  

Significance of minimal residual disease in monitoring recurrence of pediatric acute lymphoblastic leukemia

作　　者：顿建新 丁玉亭 张艾[1] 王雅琴[1] 刘爱国[1] 胡群[1] DUN Jianxin;DING Yuting;ZHANG Ai;WANG Yaqin;LIU Aiguo;HU Qun(Department of Pediatric Hematology,Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院儿童血液科,武汉430030

出　　处：《中国循证儿科杂志》2024年第3期179-182,共4页Chinese Journal of Evidence Based Pediatrics

摘　　要：背景微小残留病变(MRD)用于监测和评估儿童急性淋巴细胞白血病(ALL)的治疗反应,并根据MRD水平进行危险度分层。目的探讨ALL患儿化疗期间及结束化疗后定期监测MRD对复发的预后价值。设计回顾性队列研究。方法收集2015年1月至2020年2月华中科技大学同济医学院附属同济医院(我院)接受CCCG-ALL 2015方案化疗的初诊ALL连续病例的临床资料,使用流式细胞术检测MRD。分析定期监测MRD与早期预测复发之间的关系。主要结局指标无复发生存期(RFS)。结果224例患儿纳入本文分析,男134例,女90例,中位年龄4.8岁。①诱导缓解第19天(D19)MRD阳性104例(46.4%),第46天(D46)MRD阳性23例(10.3%)。从诱导缓解后(16周)至结束化疗(125周)MRD均阴性145例。结束化疗后随访期间(152~287周),13例MRD阳性,其中11例(84.6%)复发。②28例患儿复发,中位复发时间33月,14例存活,12例死亡,2例失访;20例骨髓复发,其中2例合并睾丸复发,1例合并中枢神经系统复发(CNSL);8例单纯CNSL。③224例患儿随访时间52(IQR:36.5~69.5)月,5年RFS(84.5±2.8)%。D46 MRD≥0.01%与<0.01%、诱导缓解后至结束化疗期间MRD均阴性与MRD至少1次阳性患儿的5年RFS差异均有统计学意义(P<0.05)。结论D46 MRD≥0.01%及诱导缓解后至结束化疗期间MRD至少1次阳性的患儿预后较差。化疗过程中定期监测MRD十分重要。Background Minimal residual disease(MRD)is used to monitor and assess the treatment response in pediatric acute lymphoblastic leukemia(ALL)and to stratify risk based on MRD levels.Objective To investigate the prognostic value of regularly monitoring MRD during and after chemotherapy in predicting relapse in children with ALL.Design Retrospective cohort study Methods The clinical data of 224 ALL children received CCCG-ALL2015 chemotherapy from January 2015 to February 2020 were retrospectively included in our study.MRD was detected using flow cytometry to analyze the association between regular monitoring of MRD and prediction of recurrence.Main outcome measures Recurrence free survival(RFS)Results A total of 224 children were included in this analysis,with 134 males and 90 females,and a median age of 4.8 years.On day 19(D19)of induction remission,104 cases(46.4%)were MRD-positive,and on day 46(D46),23 cases(10.3%)were MRD-positive.From post-induction remission(week 16)to the end of chemotherapy(week 125),145 cases remained MRD-negative.During follow-up after the end of chemotherapy(weeks 152-287),13 cases became MRD-positive,of which 11(84.6%)relapsed.A total of 28 children relapsed,with a median relapse time of 33 months.Among them,14 survived,12 died,and 2 were lost to follow-up.There were 20 cases of bone marrow relapse,including 2 with concurrent testicular relapse and 1 with CNSL and 8 with CNSL alone.The median follow-up time for the 224 children was 52 months(IQR:36.5-69.5 months),and the 5-year RFS was(84.5±2.8)%.There were statistically significant differences in the 5-year RFS between children with D46 MRD≥0.01%and<0.01%,as well as between those who remained MRD-negative throughout chemotherapy and those who were MRD-positive at least once(P<0.05).Conclusion Children with D46 MRD≥0.01%and those who were MRD-positive at least once during chemotherapy had a poorer prognosis.Regular MRD monitoring during chemotherapy is crucial.

关 键 词：儿童 急性淋巴细胞白血病 微小残留病变 复发 

分 类 号：R733.71[医药卫生—肿瘤]