动态监测RUNX1-RUNX1T1转录本水平在儿童急性髓系白血病中的预后价值

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.