title: Single cycle of arsenic trioxide-based consolidation chemotherapy spares anthracycline exposure in the primary management of acute promyelocytic leukemia.
abstract: PURPOSE Event-free survival following all-trans-retinoic acid (ATRA) -based therapy for acute promyelocytic leukemia (APL) averages 70% at 5 years. While arsenic trioxide (ATO) can induce remissions in 95% of relapsed patients, few studies have addressed the integration of ATO into the primary management of APL. This study examines the efficacy of a single cycle of ATO-based consolidation therapy in a treatment regimen designed to decrease exposure to other cytotoxic agents. PATIENTS AND METHODS After induction with ATRA and daunorubicin (DRN), untreated patients with APL received 3 days of cytarabine and DRN followed by 30 doses of ATO beginning on day 8. Molecular remitters received 2 years of risk-based maintenance therapy. Results Forty-one of 45 patients receiving induction therapy achieved remission; four patients died (one before treatment was initiated). Thirty-seven patients received consolidation and maintenance; of these one patient relapsed (CNS) and one died in remission during maintenance therapy (hepatic sickle cell crisis). With a median follow-up of 2.7 years, estimated disease-free survival was 90%; overall survival for all patients was 88%. Despite a total anthracycline dose of only 360 mg/m(2), cardiac ejection fraction decreased by > or = 20% in 20% of patients. CONCLUSION These data, combined with other recent studies using ATO in the primary management of APL, demonstrate the important role that ATO can play in the primary management of this curable disease. Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, CRB1-288, 1650 Orleans St, Baltimore, MD 21231, USA. gorest@jhmi.edu
authors.forename: Steven D
authors.initials: SD
authors.lastname: Gore
authors.forename: Ivana
authors.initials: I
authors.lastname: Gojo
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.forename: Lawrence
authors.initials: L
authors.lastname: Morris
authors.forename: Marcel
authors.initials: M
authors.lastname: Devetten
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jamieson
authors.forename: Robert L
authors.initials: RL
authors.lastname: Redner
authors.forename: Robert
authors.initials: R
authors.lastname: Arceci
authors.forename: Ibitayo
authors.initials: I
authors.lastname: Owoeye
authors.forename: Tianna
authors.initials: T
authors.lastname: Dauses
authors.forename: Esther
authors.initials: E
authors.lastname: Schachter-Tokarz
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gallagher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D010087:Oxides / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001152:Arsenicals; D010087:Oxides; D003561:Cytarabine; D014212:Tretinoin; D000077237:Arsenic Trioxide; D003630:Daunorubicin