Significance of Quantification of the PML-RARa Transcript in Children with Acute Promyelocytic Leukemia: A Single Center Experience

Minimal residual disease (MRD) monitoring based on the detection of PML/RARa transcripts employing PCR technology has clearly demonstrated its benefit in the diagnosis and follow-up of acute promyelocytic leukemia (APL) patients. So far, real-time quantitative PCR (RQ-PCR) has been investigated to provide prognostic indexes for APL management in many adults studies. However, there are still no data on the use of such assays for child APL therapy. The aim of this study was conducted to clarify the relationship between the level of MRD and outcome in children with newly diagnosed PML/RARa-positive APL and identify the subgroups at low-risk of relapse.

Since January 2004, we have analyzed 40 child patients treated with all-trans-retinoic acid (ATRA)±arsenic trioxide (ATO) in induction, with a median follow-up of 47 months. They were monitored by RQ-PCR. Hematologic and molecular relapses were recorded. We then looked for associations between relapse risk and RQ-PCR results in children.

The pretreatment characteristics of the 40 patients are listed in Table 1. Thirty-nine patients (97.5%) entered complete remission (CR). The 5-year probabilities of disease-free survival (DFS) and overall survival (OS) were 73.1% and 91.4%, respectively. By employing the standardized real-time quantitative polymerase chain reaction (RQ-PCR) for minimal residual disease (MRD) monitoring, no significant difference were observed in the PML/RARa normalized copy number (NCN) between patients in continuous complete remission and those who relapsed (neither at diagnosis nor after induction). After induction therapy, eight out of 25 cases with positive RQ-PCR (more than 1 NCN) relapsed in contrast to none out of 13 patients with negative RQ-PCR(100% and 55.2% DFS at 5 years in the negative and positive RQ-PCR groups, respectively; P=0.018, Fig.1). Also of note, in the positive RQ-PCR group, the patients treated with ATRA+ATO in induction had a lower relapse rate when compared with those treated with ATRA alone (P=0.03).

PML/RARa - based MRD monitoring by RQ-PCR might allow us to identify subgroups of patients at low risk of relapse after induction in childen. Patients with a low risk of relapse could be monitored less frequently. Combination of ATO and ATRA might decrease the relapse rate compared with ATRA alone in induction therapy for childhood APL.

Fig. 1.

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The 5-year disease-free survival of patients with a different PML/RARa normalized copy number by RQ-PCR after induction.

Fig. 1.

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The 5-year disease-free survival of patients with a different PML/RARa normalized copy number by RQ-PCR after induction.

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No relevant conflicts of interest to declare.