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
Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
Oncotarget. 2015 May 30;6(15):13269-77. doi: 10.18632/oncotarget.3773.
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.
在本研究中，我们通过液滴数字聚合酶链反应（ddPCR）对76例新诊断的急性早幼粒细胞白血病（APL）病例中的PML-RARA转录本进行了绝对定量，以验证PML-RARA初始分子负荷的预后影响。ddPCR分析显示，复发患者组诊断时的PML-RARA转录本量高于持续完全缓解（CCR）组（分别为272与89.2个PML-RARA拷贝/ng，p = 0.0004）。受试者工作特征分析检测到区分结局（CCR与复发）的最佳PML-RARA浓度阈值为209.6个PML-RARA/ng（AUC 0.78；p < 0.0001）。在诱导治疗后达到完全缓解的67例APL病例中，PML-RARA/ng > 209.6的患者无复发生存期较差（p = 0.0006）。在5年随访时，PML-RARA/ng > 209.6的患者累积复发率为50.3%，而PML-RARA/ng较低的患者复发率为7.5%（p < 0.0001）。多变量分析确定诱导治疗前的PML-RARA量是APL复发的唯一独立预后因素。我们的结果表明，预处理时的PML-RARA分子负荷可用于改善风险分层，以便为高危APL病例制定更个体化的治疗方案。
