title: Absolute quantification of the pretreatment PML-RARA transcript defines the relapse risk in acute promyelocytic leukemia.
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 < 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.
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Albano
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Zagaria
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Anelli
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Coccaro
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Tota
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Brunetti
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Crescenzio Francesco
authors.initials: CF
authors.lastname: Minervini
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Impera
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Minervini
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Cellamare
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Orsini
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Cumbo
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Casieri
authors.affiliation: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124, Bari, Italy.
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016016:Proportional Hazards Models; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
keywords: PML-RARA; acute promyelocytic leukemia; droplet digital PCR; prognostic factor; relapse risk