Absolute quantification of the pretreatment<i>PML-RARA</i>transcript defines the relapse risk in acute promyelocytic leukemia

Abstract

// Francesco Albano 1 , Antonella Zagaria 1 , Luisa Anelli 1 , Nicoletta Coccaro 1 , Giuseppina Tota 1 , Claudia Brunetti 1 , Crescenzio Francesco Minervini 1 , Luciana Impera 1 , Angela Minervini 1 , Angelo Cellamare 1 , Paola Orsini 1 , Cosimo Cumbo 1 , Paola Casieri 1 , Giorgina Specchia 1 1 Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy Correspondence to: Francesco Albano, e-mail: francesco.albano@uniba.it Keywords: acute promyelocytic leukemia, PML-RARA, relapse risk, droplet digital PCR, prognostic factor Received: February 25, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: April 06, 2015&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: April 18, 2015 ABSTRACT In this study we performed absolute quantification of the PML-RARA transcript by droplet digital polymerase chain reaction (ddPCR) in 76 newly diagnosed acute promyelocytic leukemia (APL) cases to verify the prognostic impact of the PML-RARA initial molecular burden. ddPCR analysis revealed that the amount of PML-RARA transcript at diagnosis in the group of patients who relapsed was higher than in that with continuous complete remission (CCR) (272 vs 89.2 PML-RARA copies/ng, p = 0.0004, respectively). Receiver operating characteristic analysis detected the optimal PML-RARA concentration threshold as 209.6 PML-RARA /ng (AUC 0.78; p &lt; 0.0001) for discriminating between outcomes (CCR versus relapse). Among the 67 APL cases who achieved complete remission after the induction treatment, those with &gt;209.6 PML-RARA /ng had a worse relapse-free survival ( p = 0.0006). At 5-year follow-up, patients with &gt;209.6 PML-RARA /ng had a cumulative incidence of relapse of 50.3% whereas 7.5% of the patients with suffered a relapse ( p &lt; 0.0001). Multivariate analysis identified the amount of PML-RARA before induction treatment as the sole independent prognostic factor for APL relapse. Our results show that the pretreatment PML-RARA molecular burden could therefore be used to improve risk stratification in order to develop more individualized treatment regimens for high-risk APL cases.