title: A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group.
abstract: The Spanish PETHEMA group designed a protocol for newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia (APL) in which induction and consolidation followed the original AIDA regimen, except for the omission of cytarabine and etoposide from consolidation. Induction consisted of 45 mg/m(2) all-trans retinoic acid (ATRA) daily until complete remission (CR) and 12 mg/m(2) idarubicin on days 2, 4, 6, and 8. Patients in CR received 3 monthly chemotherapy courses: idarubicin 5 mg/m(2)/d x 4 (course no. 1), mitoxantrone 10 mg/m(2)/d x 5 (course no. 2), and idarubicin 12 mg/m(2)/d x 1 (course no. 3). Maintenance therapy consisted of 90 mg/m(2)/d mercaptopurine orally, 15 mg/m(2)/wk methotrexate intramuscularly, and, intermittently, 45 mg/m(2)/d ATRA for 15 days every 3 months. Between November 1996 and December 1998, 123 patients with newly diagnosed PML/RARalpha-positive APL from 39 centers were enrolled. A total of 109 patients achieved CR (89%; 95% confidence interval [CI], 83 to 95), 12 died of early complications, and the remaining 2 were resistant. Consolidation treatment was associated with very low toxicity and no deaths in remission were recorded. Molecular assessment of response by reverse transcriptase-polymerase chain reaction (RT-PCR) showed conversion to PCR-negative in 48 of 99 (51%) and 82 of 88 patients (93%) after induction and consolidation, respectively. The 2-year Kaplan-Meier estimates of overall survival and event-free survival were 82% +/- 4% and 79% +/- 4%, respectively. For patients who achieved CR, the 2-year disease-free survival (DFS) was 92% +/- 3%. These data indicate that a significant reduction in toxicity might be obtained in APL using a less intensive consolidation without apparently compromising the antileukemic effect. These results also suggest a minor role for cytarabine and etoposide in the treatment of newly diagnosed PML/RARalpha-positive APL patients.
authors.affiliation: Servicio de Hematología, Hospital Universitario La Fe, Valencia, Spain. msanz@uv.es
authors.forename: M A
authors.initials: MA
authors.lastname: Sanz
authors.forename: G
authors.initials: G
authors.lastname: Martín
authors.forename: C
authors.initials: C
authors.lastname: Rayón
authors.forename: J
authors.initials: J
authors.lastname: Esteve
authors.forename: M
authors.initials: M
authors.lastname: González
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: P
authors.initials: P
authors.lastname: Bolufer
authors.forename: E
authors.initials: E
authors.lastname: Barragán
authors.forename: M J
authors.initials: MJ
authors.lastname: Terol
authors.forename: J D
authors.initials: JD
authors.lastname: González
authors.forename: D
authors.initials: D
authors.lastname: Colomer
authors.forename: C
authors.initials: C
authors.lastname: Chillón
authors.forename: C
authors.initials: C
authors.lastname: Rivas
authors.forename: T
authors.initials: T
authors.lastname: Gómez
authors.forename: J M
authors.initials: JM
authors.lastname: Ribera
authors.forename: R
authors.initials: R
authors.lastname: Bornstein
authors.forename: J
authors.initials: J
authors.lastname: Román
authors.forename: M J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: J
authors.initials: J
authors.lastname: Arias
authors.forename: C
authors.initials: C
authors.lastname: Alvarez
authors.forename: F
authors.initials: F
authors.lastname: Ramos
authors.forename: G
authors.initials: G
authors.lastname: Debén
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D018943:Anthracyclines; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D015255:Idarubicin