南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (02): 255-261.doi: 10.12122/j.issn.1673-4254.2020.02.19

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第19天微小残留病检测在儿童急性淋巴细胞白血病中的预后意义及危险因素分析

余洁明，易甜甜，林贯川，温建芸，陈丽白，陈佳奇，吴学东   

  • 出版日期:2020-03-14 发布日期:2020-02-20
  • 基金资助:

Prognostic significance and risk factors of minimal residual disease ≥1% on 19th day of induction chemotherapy in children with acute lymphoblastic leukemia

  

  • Online:2020-03-14 Published:2020-02-20

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摘要： 目的 探讨使用中国抗癌协会儿童肿瘤协作组（CCCG）急性淋巴细胞白血病（ALL）2015方案治疗的患儿中，第19天微小残留病（D19 MRD）≥1%作为评价早期治疗反应对预后的意义及其风险因素。方法 回顾性分析2015年1月1日至2018年12月31日在本中心使用该方案治疗的ALL患儿病历资料共243例。以诱导化疗D19 MRD≥1%为节点，分为早期治疗反应良好 （D19 MRD<1%）组和早期治疗反应不良（D19 MRD≥1%）组。比较两组生存时间的差异并分析D19 MRD≥1%的风险因素。结果 D19 MRD<1%组3年总生存率（OS）优于D19 MRD≥1%组（100% vs 90.2%，P=0.004）。D19 MRD<1%组3年无事件生存 率（EFS）优于D19 MRD≥1%组（97.6% vs 71.6%，P<0.001）。单因素分析表明纵膈侵犯，T-细胞免疫分型、TEL/AML1（ETV6/RUNX1）融合基因及第5天外周血存在幼稚细胞的风险系数（OR）及95%置信区间（CI）分别是4.47（0.275~72.968，P=0.034）、 5.250（1.950~14.133，P=0.02）、0.330（0.112~0.970，P=0.036）及4.407（1.782~10.895，P=0.01）。初治危险度（P<0.001），初治白细胞计数分等级间（P=0.018）及其数量（P=0.027），第5天幼稚细胞数量（P<0.001）在两组间均有差异。多因素分析表明初治危险度为中高危，第5天外周血存在幼稚细胞是D19 MRD≥1%的独立风险因素，其OR及其95%CI分别是2.889（1.193~6.996，P=0.019）、4.477（1.692~11.843，P=0.003）。结论 D19 MRD≥1%是影响预后的因素；纵膈侵犯、T细胞免疫分型及第5天外周血存在幼稚细胞是风险因素，而TEL/AML1融合基因是保护因素；中高危及第5天外周血存在幼稚细胞为独立风险因素。

Abstract: Objective To assess the prognostic value of minimal residual disease on 19th day of induction chemotherapy (D19 MRD) and the risk factors of D19 MRD ≥1% in children with acute lymphoblastic leukemia (ALL) treated following the Chinese Children’s Cancer Group ALL protocol. Methods We retrospectively analyzed the data of 243 children with ALL diagnosed between January 1, 2015 and December 31, 2018 in the Department of Pediatrics of Nanfang Hospital (Guangzhou China). Kaplan Meier-survival analysis was performed to compare the survival time between the patients with D19 MRD <1% and those with D19 MRD ≥1%; logistic regression analyisis and Chi-square test were used to identify the risk factors of D19 MRD ≥1%. Results Compared with those with D19 MRD≥1%, the children with D19 MRD<1% had significantly better 3-year overall survival (100% vs 90.2%, P=0.004) and event-free survival (97.6% vs 71.6%, P<0.001). Univariate analysis showed that the odds ratio (OR) for mediastinal invasion, T-cell immunophenotype, TEL/AML1 fusion gene and the presence of blasts in peripheral blood on the 5th day were 4.47 (95%CI: 0.275-72.968, P=0.034), 5.250 (95%CI: 1.950-14.133, P=0.02), 0.330 (95%CI: 0.112-0.970, P=0.036) and 4.407 (95%CI: 1.782-10.895, P=0.01), respectively. The initial risk stratification (P<0.001), white blood cell grades (P=0.018) and its counts (P=0.027), and the number of blasts on the 5th day (P<0.001) were significantly different between the two groups. Multivariate analysis showed that initial risk stratification as intermediate and high risks (OR=2.889, 95% CI: 1.193-6.996) and the presence of blasts in peripheral blood on the 5th day (OR=4.477, 95% CI: 1.692-11.843) were independent risk factors for poor early treatment response. Conclusion D19 MRD ≥1% is a predictor of poor prognosis in children with ALL. Mediastinal invasion, T-cell immunophenotype and the presence of blasts in peripheral blood on the 5th day are all risk factors for poor early treatment response, while TEL/AML1 fusion gene is a protective factor; the initial risk stratification as intermediate to high risk and the presence of blasts in peripheral blood on the 5th day are independent risk factors for poor early treatment response of the patients.