ABSTRACT
Objective To explore the prognostic value of quantitative monitoring of RUNX1-RUNX1T1 fusion gene in pediatric t(8;21)/RUNX1-RUNX1T1 positive acute myeloid leukemia(AML).Methods A total of 81 new-ly diagnosed AML children with t(8;21)/RUNX1-RUNX1T1 positive were enrolled in the People′s Hospital,Peking University,between August 2005 and January 2016.RUNX1-RUNX1T1 gene copy number of all the patients was analyzed by real-time quantitative PCR(qPCR)technology at diagnosis and after therapy in all patients.Cumulative incidence of relapse rate(CIR),event-free survival(EFS)rate and overall survival(OS)rate were estimated by Ka-plan-Meier method and prognostic factors were evaluated by COX regression. Results The level of RUNX1-RUNX1T1 gene on diagnosis was used as the baseline to determine whether the level of gene after treatment had a more than 3 logarithmic(3 log)reduction.After 2 courses of induction therapy,the patients with a more than 3 log reduction of RUNX1-RUNX1T1 transcript levels(≥3 log)had better EFS rate(82.4% vs.57.6%,χ2=7.454,P<0.01),and better OS(93.6% vs.59.3%,χ2=9.703,P<0.01),compared to the patients with a less than 3 log reduction(<3 log).Multivariate analysis showed that 3 log reduction in RUNX1-RUNX1T1 transcript levels after 2 courses of in-duction therapy was an independent prognostic factor for EFS rate[hazard ratio(HR)=4.223,95% confidence interval (CI):1.507-11.836,P<0.01]and OS rate(HR=5.002,95%CI:1.282-19.516,P<0.05).When periodically monitoring the RUNX1-RUNX1T1 gene,63 out of the 81 children patients were monitored for more than 6 times.The patients who had a more than 3 log reduction of gene before,but then those whose gene transcript level rose more than 1 log level were divided into group A,and the remaining patients were divided group B,and the difference of CIR was statistically significant between group A and group B(46. 7% vs. 4. 7%,P <0. 01). Conclusions RUNX1-RUNX1T1 gene copy number was detected with qPCR method in pediatric t(8;21)/RUNX1-RUNX1T1 positive AML,which can determine the treatment effect,predict the recurrence of patients and assess long-term prognosis.Thus it has great clinical application value.
ABSTRACT
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) %, 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>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.