title: All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol.
abstract: We previously reported a benefit for all-trans retinoic acid (ATRA) in both induction and maintenance therapy in patients with acute promyelocytic leukemia (APL). To determine the durability of this benefit and identify important prognostic factors, long-term follow-up of the North American Intergroup APL trial is reported. A total of 350 patients with newly diagnosed APL were randomized to either daunorubicin and cytarabine (DA) or ATRA for induction and then either ATRA maintenance or observation following consolidation chemotherapy. The complete remission (CR) rates were not significantly different between the ATRA and DA groups (70% and 73%, respectively). However, the 5-year disease-free survival (DFS) and overall survival (OS) were longer with ATRA than with DA for induction (69% vs 29% and 69% vs 45%, respectively). Based on both induction and maintenance randomizations, the 5-year DFS was 16% for patients randomized to DA and observation, 47% for DA and ATRA, 55% for ATRA and observation, and 74% for ATRA and ATRA. There was no advantage of either induction regimen among any subgroups when CR alone was considered. However, female sex, classical M3 morphology (vs the microgranular variant [M3v]), and treatment-white blood cell count (WBC) interaction (ATRA/WBC below 2 x 10(9)/L [2000/microL] best, DA/WBC above 2 x 10(9)/L worst) were each significantly associated with improved DFS (P <.05). Treatment with ATRA, WBC below 2 x 10(9)/L, and absence of bleeding disorder were each significantly associated with improved OS. Age more than 15 years, female sex, and treatment-morphology interaction (DA/M3v worst, ATRA best regardless of morphology) were each significantly associated with improved DFS based on maintenance randomization. The improvement in outcome with ATRA in APL was maintained with long-term follow-up.
authors.affiliation: Northwestern University, Feinburg School of Medicine, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA. m-tallman@northwestern.edu
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Janet W
authors.initials: JW
authors.lastname: Andersen
authors.forename: Charles A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: James H
authors.initials: JH
authors.lastname: Feusner
authors.forename: William G
authors.initials: WG
authors.lastname: Woods
authors.forename: Angela
authors.initials: A
authors.lastname: Ogden
authors.forename: Howard
authors.initials: H
authors.lastname: Weinstein
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.forename: Cheryl
authors.initials: C
authors.lastname: Willman
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wiernik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D007958:Leukocyte Count; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D014212:Tretinoin; D003630:Daunorubicin