摘要目的 探讨动态监测RUNX1-RUNX1T1转录本水平在儿童t(8;21)急性髓系白血病(AML)预后评估中的价值.方法 以2010年1月至2016年4月就诊于郑州大学人民医院的55例儿童t(8;21)AML患者为研究对象,应用实时荧光定量PCR(RQ-PCR)动态监测患者的RUNX1-RUNX1T1转录本水平,分析其变化与疾病预后的关系.结果 初诊时患者骨髓细胞中的RUNX1-RUNX1T1转录本水平与复发及预后无关.1个疗程诱导缓解治疗后,骨髓细胞中RUNX1-RUNX1T1转录本水平比诊断时下降大于2个对数级(a>2 Log)者与a≤2 Log者相比:5年累积复发率(CIR)分别为(24.3±8.4)%及(52.6±9.7)%(χ2=9.046,P=0.003),5年无复发生存(RFS)率分别为(71.6±12.7)%及(48.1±13.2)%(χ2=5.814,P=0.016),5年总生存(OS)率分别为(76.9±12.5)%及(48.9±14.7)%(χ2=6.346,P=0.012),差异均有统计学意义.多因素Cox回归模型结果显示,1个疗程诱导缓解后RUNX1-RUNX1T1转录本下降是否大于2 Log是影响RFS(HR=0.263,95%CI 0.081~0.851,P=0.026)与OS(HR=0.214,95%CI 0.057~0.808,P=0.023)的独立预后因素.巩固治疗及治疗结束随访期间动态监测RUNX1-RUNX1T1转录本水平变化,共有16例患者发生分子学复发,其中13例患者发生了血液学复发,分子学复发至血液学复发的中位时间为4.0(1.5~5.8)个月.对2例分子学复发后的患者及时采取异基因造血干细胞移植治疗后,患者未发生血液学复发.结论 通过RQ-PCR动态监测儿童t(8;21)AML患者的RUNX1-RUNX1T1转录本水平,可以将儿童t(8;21)AML细分为相对低危组和相对高危组并提前预测血液学复发,为实现儿童t(8;21)AML的精准分层和风险-适应治疗提供科学依据.

abstractsObjective To investigate the prognostic value of dynamic monitoring of RUNX1-RUNX1T1 transcript in pediatric patients with t(8;21)acute myeloid leukemia(AML). Methods The clinical features and RUNX1-RUNX1T1 transcript levels of 55 pediatric t(8;21) AML patients, newly diagnosed from Jan. 2010 to Apr. 2016, were analyzed retrospectively. The relationship between the minimal residual disease (MRD) and prognosis was analysed by dynamic monitoring of RUNX1-RUNX1T1 transcript levels using real-time quantitative PCR (RQ-PCR) technology. Results The RUNX1-RUNX1T1 transcript levels in bone marrow cells at diagnosis was not related to relapse. After one course of induction therapy, patients with a more than 2 Log reduction of RUNX1-RUNX1T1 transcript levels(>2 Log)had lower 5 years cumulative incidence of relapse(CIR)[(24.3±8.4)%vs(52.6±9.7)%,χ2=9.046, P=0.003], relapse-free survival(RFS)[(71.6 ± 12.7)%vs(48.1 ± 13.2)%,χ2=5.814, P=0.016], and better overall survival (OS)[(76.9 ± 12.5)% vs (48.9 ± 14.7)%, χ2=6.346, P=0.012], compared to patients with a less than 2 Log reduction(a<2 Log). Multivariate Cox survival analysis suggested that a>2Log reduction in RUNX1- RUNX1T1 transcript levels after a course of induction therapy was an independent prognostic factor for RFS(HR=0.263, 95%CI 0.081-0.851, P=0.026)and OS(HR=0.214, 95%CI 0.057-0.808, P=0.023). During consolidation therapy and follow-up period, molecular relapse of 16 cases and hematologic relapse of 13 cases were identified by continuous dynamic monitoring of RUNX1-RUNX1T1 transcript levels, with a median interval of 4.0(1.5-5.8)months from the molecular relapse to hematologic relapse. 2 cases of molecular relapse who received timely allogeneic hematopoietic stem cell transplantation did not experience hematologic relapse. Conclusion Dynamic monitoring RUNX1-RUNX1T1 transcript levels by RQ-PCR technique can subdivide patients into relatively low and high risk group, early screen patients at high risk of relapse and provide a scientific basis for precision stratification and risk-adapted therapy for pediatric t(8;21)AML children.