title: 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.
abstract: OBJECTIVE
  To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML).
  
  
  METHODS
  Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age > or = 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age > or = 60 years) x 8 instead of maintenance.
  
  
  RESULTS
  A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P =.0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P =.085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P =.026).
  
  
  CONCLUSIONS
  We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.
authors.affiliation: University Medical Center, Department of Medicine, Hematology and Oncology, University of Muenster, Ulbert-Schweitzer-Str 33, D-48129 Muenster, Germany. buechnr@uni-muenster.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Büchner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wörmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Schoch
authors.forename: Christa
authors.initials: C
authors.lastname: Fonatsch
authors.forename: Helmut
authors.initials: H
authors.lastname: Löffler
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: Georg
authors.initials: G
authors.lastname: Maschmeyer
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Carlo
authors.initials: C
authors.lastname: Aul
authors.forename: Andreas
authors.initials: A
authors.lastname: Gruneisen
authors.forename: Eva
authors.initials: E
authors.lastname: Lengfelder
authors.forename: Norbert
authors.initials: N
authors.lastname: Frickhofen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Hubert L
authors.initials: HL
authors.lastname: Serve
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Mesters
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Sauerland
authors.forename: Achim
authors.initials: A
authors.lastname: Heinecke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone; D013866:Thioguanine; D003630:Daunorubicin