title: All-trans retinoic acid with daunorubicin or idarubicin for risk-adapted treatment of acute promyelocytic leukaemia: a matched-pair analysis of the PETHEMA LPA-2005 and IC-APL studies.
abstract: Front-line treatment of acute promyelocytic leukaemia (APL) consists of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. In this setting, a comparison of idarubicin and daunorubicin has never been carried out. Two similar clinical trials using ATRA and chemotherapy for newly diagnosed APL were compared using matched-pair analysis. One was conducted by the PETHEMA/HOVON group with idarubicin and the other by the International Consortium on APL (IC-APL) using daunorubicin. Three hundred and fifty patients from the PETHEMA/HOVON cohort were matched with 175 patients in the IC-APL cohort, adjusting for the significantly unbalanced presenting features of the two entire cohorts. Complete remission (CR) rate was significantly higher in the PETHEMA/HOVON (94 %) than in the IC-APL cohort (85 %) (P = 0.002). The distribution of causes of induction failure and the time to achieve CR were similar in both cohorts. Patients who achieved CR had comparable cumulative incidence of relapse and disease-free survival rates, but lower overall and event-free survivals were observed in the IC-APL cohort, which was mainly due to a higher death rate during induction therapy. A higher death rate during consolidation therapy was also observed in the IC-APL. These results show that daunorubicin and idarubicin have similar antileukaemic efficacy in terms of primary resistance, molecular persistence, as well as molecular and haematological relapse rates when combined with ATRA in treatment of APL. However, a higher toxic death rate during induction and consolidation therapy was observed in the IC-APL cohort. This trial was registered at www.clinicaltrials.gov as #NCT00408278 [ClinicalTrials.gov].
authors.affiliation: Hematology Department, University Hospital La Fe, Avinguda Fernando Abril Martorell, 106, 46026, Valencia, Spain, msanz@uv.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Ruiz-Argüelles
authors.forename: María S
authors.initials: MS
authors.lastname: Undurraga
authors.forename: María R
authors.initials: MR
authors.lastname: Uriarte
authors.forename: Lem
authors.initials: L
authors.lastname: Martínez
authors.forename: Rafael H
authors.initials: RH
authors.lastname: Jacomo
authors.forename: Homero
authors.initials: H
authors.lastname: Gutiérrez-Aguirre
authors.forename: Raul A M
authors.initials: RA
authors.lastname: Melo
authors.forename: Rosane
authors.initials: R
authors.lastname: Bittencourt
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pasquini
authors.forename: Katia
authors.initials: K
authors.lastname: Pagnano
authors.forename: Evandro M
authors.initials: EM
authors.lastname: Fagundes
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Alexandra
authors.initials: A
authors.lastname: Holowiecka
authors.forename: Ana J
authors.initials: AJ
authors.lastname: González-Huerta
authors.forename: Pascual
authors.initials: P
authors.lastname: Fernández
authors.forename: Javier
authors.initials: J
authors.lastname: De la Serna
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Elena
authors.initials: E
authors.lastname: De Lisa
authors.forename: José
authors.initials: J
authors.lastname: González-Campos
authors.forename: José M
authors.initials: JM
authors.lastname: Ribera
authors.forename: Isabel
authors.initials: I
authors.lastname: Krsnik
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Nancy
authors.initials: N
authors.lastname: Berliner
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Rego
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014212:Tretinoin; D015255:Idarubicin; D003630:Daunorubicin