Detection Of Minimal Residual Disease In Childhood With Acute Promyelocytic Leukemia By Real-time Quantitative PCR

Detection of minimal residual disease in childhood with acute promyelocytic leukemia by real-time quantitative PCR[Abstract] Objective The detection of PML/RARαby real-time polymerase chain reaction (RQ-PCR) is becoming an important tool for monitoring minimal residual disease (MRD) in patients with acute promyelocytic leukemia (APL). However, its benefit in children remains to be determined. Our aim was to analyze any associations between the risk of relapse and RQ-PCR results in different phases of treatment, comparing these data with those yielded by conventional qualitative reverse transcriptase-PCR.Methods Real-time polymerase chain reaction (RQ-PCR) and/or regular reverse transcription polymerase chain reaction(RT-PCR)were used to analyzed blood or marrow samples from 49 children with newly diagnosed acute promyelocytic leukemia. All the TaqMan probe-based RQ-PCR reactions and analysis were performed on an ABI-PRISM 7500 platform. Hematologic and molecular relapses were recorded. We then looked for associations between relapserisk and RQ-PCR results. Data were analyzed with SPSS system software.Result Thirty-eight boys and 11 girls were included in this study. The median age at diagnosis was 9(1.5-16) years old. The WBC count at presentation was more than 10×109/L in 16 patients (32.7%). Forty-seven children (98.0%) achieved complete remission (CR). Early death from hemorrhage occurred in one patient. The 5-year event-free, disease-free and overall survival rates were 72.0%,73.5% and 98.0%, respectively. PML/RAR a fusion transcripts were detected in 47 (98%) patients. Of 47 patients, 34 (72.3%) had the L isoform,3 (6.4%) had the V isoform and 10 (21.2%) had the S isoform. We observed the significant PML/RARαNCN variance in the pretreatment samples between individual patients. Patients treated with the protocol before 2010 were identified into 2 groups according to the different induction medication. Twenty patients were given ATRA alone (group-1) and 5 patients were treated with ATO+ATRA (group-2). Though the 5-year estimate of DFS between group-land group-2 had no statistically significant difference (P=0.160), there was a 30% higher DFS rate for group-2. ATO+ATRA might decrease the relapse rate when compared with ATRA alone in induction therapy of childhood APL. No false negative results occurred in 274 samples when tested by RQ-PCR. After induction therapy, none out of 13 cases with negative RQ-PCR relapsed in contrast to 8 out of 25 patients with positive RQ-PCR. The disease-free survival at 5 years was 100% and 40.3±18.3% (P=0.06), respectively. In the patients with positive RQ-PCR, the relapse rate was lower in those patients treated with arsenic trioxide in induction.Conclusion The RQ-PCR assay is reliable for the detection of PML-RAR a transcripts. Detection of PML-RAR a fusion gene can be relaxed a little. Treated with ATRA combined with arsenic trioxide for induce therapy provided favorable results in children with APL.