title: Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up.
abstract: Shortly before the all-trans retinoic acid (ATRA) era, the GIMEMA cooperative group initiated a randomized study comparing idarubicin (IDA) alone with IDA plus arabinosylcytosine (Ara-C) as induction treatment in patients with newly diagnosed hypergranular acute promyelocytic leukemia (APL). Of the 257 patients evaluable for induction treatment, 131 were randomized to receive IDA alone (arm A) and 126 to receive IDA + Ara-C (arm B). Treatment in arm A consisted of 10 mg/m(2) IDA daily for 6 consecutive days, whereas in arm B it consisted of 12 mg/m(2) IDA daily for 4 days combined with 200 mg/m(2) Ara-C daily in continuous infusion for 7 days. Once in complete remission (CR), patients received 3 consolidation courses of standard chemotherapy, and those still in CR at the end of the consolidation were randomized to receive or not receive 1 mg/kg 6-mercaptopurine daily and intramuscular injections of 0.25 mg/kg methotrexate weekly for 2 years. Overall, 100 (76.3%) patients in arm A and 84 (66.6%) patients in arm B achieved CR (P = NS). Event-free survival (EFS) rates were 35% and 23% for patients in arm A and arm B, respectively (P =.0352). Multivariate analysis revealed that EFS was favorably influenced by induction treatment with IDA alone (P =.0352) and unfavorably influenced by white blood cell (WBC) counts greater than 3000/microL (P =.0001) and increasing age (P =.0251). These results indicate that anthracycline monochemotherapy with IDA favorably influences the EFS of patients with newly diagnosed hypergranular APL.
authors.affiliation: Hematology, Università Campus-Bio-Medico, 83 Via Emilio Longoni, 00155 Rome, Italy. g.avvisati@unicampus.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Avvisati
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Petti
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: Maria Luce
authors.initials: ML
authors.lastname: Vegna
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Nicola
authors.initials: N
authors.lastname: Cantore
authors.forename: Eros
authors.initials: E
authors.lastname: Di Bona
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fioritoni
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gallo
authors.forename: Rosangela
authors.initials: R
authors.lastname: Invernizzi
authors.forename: Mario
authors.initials: M
authors.lastname: Lazzarino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Liso
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Mariani
authors.forename: Francesco
authors.initials: F
authors.lastname: Ricciuti
authors.forename: Carmine
authors.initials: C
authors.lastname: Selleri
authors.forename: Simona
authors.initials: S
authors.lastname: Sica
authors.forename: Dino
authors.initials: D
authors.lastname: Veneri
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007239:Infections / Q000209:etiology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000903:Antibiotics, Antineoplastic; D003561:Cytarabine; D015122:Mercaptopurine; D008727:Methotrexate; D015255:Idarubicin