Objective: 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) %, χ(2)=9.046, P=0.003], relapse-free survival (RFS) [ (71.6±12.7) % vs (48.1±13.2) %, χ(2)=5.814, P=0.016], and better overall survival (OS) [ (76.9±12.5) % vs (48.9±14.7) %, χ(2)=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>2 Log 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.
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）%（χ(2)=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）%（χ(2)=5.814，P=0.016），5年总生存（OS）率分别为（76.9±12.5）%及（48.9±14.7）%（χ(2)=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。.
Keywords: Child; Gene fusion, RUNX1-RUNX1T1; Leukemia, myeloid, acute; Neoplasm, residual; Prognosis.