title: High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial.
abstract: OBJECTIVE
  To assess the treatment outcome benefit of multiagent consolidation in young adults with acute myeloid leukemia (AML) in a prospective, randomized, multicenter trial.
  
  
  METHODS
  Between December 2003 and November 2009, 1,179 patients (median age, 48 years; range, 16 to 60 years) with untreated AML were randomly assigned at diagnosis to receive either standard high-dose cytarabine consolidation with three cycles of 18 g/m(2) (3× HD-AraC) or multiagent consolidation with two cycles of mitoxantrone (30 mg/m(2)) plus cytarabine (12 g/m(2)) and one cycle of amsacrine (500 mg/m(2)) plus cytarabine (10 g/m(2); MAC/MAMAC/MAC). Allogeneic and autologous hematopoietic stem-cell transplantations were performed in a risk-adapted and priority-based manner.
  
  
  RESULTS
  After double induction therapy using a 3 + 7 regimen including standard-dose cytarabine and daunorubicin, complete remission was achieved in 65% of patients. In the primary efficacy population of patients evaluable for consolidation outcomes, consolidation with either 3× HD-AraC or MAC/MAMC/MAC did not result in any significant difference in 3-year overall (69% v 64%; P = .18) or disease-free survival (46% v 48%; P = .99) according to the intention-to-treat analysis. Furthermore, MAC/MAMAC/MAC led to additional GI and hepatic toxicity and a higher rate of infection and bleeding, resulting in significantly shorter 3-year overall survival in the per-protocol analysis compared with 3× HD-AraC (63% v 72%; P = .04).
  
  
  CONCLUSIONS
  In younger adults with AML, multiagent consolidation using mitoxantrone and amsacrine in combination with high-dose cytarabine does not improve treatment outcome and confers additional toxicity.
authors: Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. markus.schaich@uniklinikum-dresden.de
authors: Markus
authors: M
authors: Schaich
authors: Stefani
authors: S
authors: Parmentier
authors: Michael
authors: M
authors: Kramer
authors: Thomas
authors: T
authors: Illmer
authors: Friedrich
authors: F
authors: Stölzel
authors: Christoph
authors: C
authors: Röllig
authors: Christian
authors: C
authors: Thiede
authors: Mathias
authors: M
authors: Hänel
authors: Kerstin
authors: K
authors: Schäfer-Eckart
authors: Walter
authors: W
authors: Aulitzky
authors: Hermann
authors: H
authors: Einsele
authors: Anthony D
authors: AD
authors: Ho
authors: Hubert
authors: H
authors: Serve
authors: Wolfgang E
authors: WE
authors: Berdel
authors: Jiri
authors: J
authors: Mayer
authors: Norbert
authors: N
authors: Schmitz
authors: Stefan W
authors: SW
authors: Krause
authors: Andreas
authors: A
authors: Neubauer
authors: Claudia D
authors: CD
authors: Baldus
authors: Johannes
authors: J
authors: Schetelig
authors: Martin
authors: M
authors: Bornhäuser
authors: Gerhard
authors: G
authors: Ehninger
mesh_terms: D000293:Adolescent; D000328:Adult; D000677:Amsacrine / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000677:Amsacrine; D003561:Cytarabine; D008942:Mitoxantrone; D003630:Daunorubicin