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

作者：Albano Francesco^*; Zagaria Antonella; Anelli Luisa; Coccaro Nicoletta; Tota Giuseppina; Brunetti Claudia; Minervini Crescenzio Francesco; Impera Luciana; Minervini Angela; Cellamare Angelo; Orsini Paola; Cumbo Cosimo; Casieri Paola; Specchia Giorgina

来源：Oncotarget, 2015, 6(15): 13269-13277.

DOI：10.18632/oncotarget.3773

• acute promyelocytic leukemia
• PML-RARA
• relapse risk
• droplet digital PCR
• prognostic factor

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 < 0.0001) for discriminating between outcomes (CCR versus relapse). Among the 67 APL cases who achieved complete remission after the induction treatment, those with > 209.6 PML-RARA/ng had a worse relapse-free survival (p = 0.0006). At 5-year follow-up, patients with > 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 < 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.

• 出版日期2015-5-30