title: Randomised Introduction of 2-CDA as Intensification during Consolidation for Children with High-risk AML--results from Study AML-BFM 2004.
abstract: BACKGROUND
  The outcome in children and adolescents with high-risk (HR) acute myeloid leukemia (AML) is still unsatisfactory. Therefore, in study AML-BFM 2004 we aimed to improve outcome of HR-patients by adding moderately dosed 2-Chloro-2-Deoxyadenosine (2-CDA) to the respective consolidation treatment backbone without increasing toxicity. The aim was to improve prognosis especially in FAB M4/M5/MLL patients, who represent the largest subgroup of HR patients.
  
  
  METHODS
  In total, 343 children and adolescents with HR-AML were randomized to receive or not 2-CDA (6 mg/m²/d, days 1, 3) in combination with cytarabine/idarubicine (AI=500 mg/m² cytarabine 5 days continuous infusion plus 7 mg/m²/d idarubicin, days 3 and 5).
  
  
  RESULTS
  RESULTS for patients of the AI/2-CDA arm (n=168) vs. the AI-arm (n=175) were similar: 5-year overall survival 68±4 vs. 72±4%, plogrank=0.38, event-free survival 53±4 vs. 49±4%, plogrank=0.77; cumulative incidence of relapse at 5 years: 35±4 vs. 37±4%, p(Gray)=0.89. RESULTS in patients with MLL rearrangement or FAB M4/M5 were also similar in the treatment groups. In addition, toxicities did not differ between the two arms.
  
  
  CONCLUSIONS
  We conclude that additional, moderate dose 2-CDA does not improve prognosis in HR-patients when given during consolidation treatment. Its effect might be too low in this multidrug regimen, where the strongest effects are achieved during induction, or the chosen dose of 2-CDA might have been too low.
authors.affiliation: Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Creutzig
authors.affiliation: St. Anna Children's Hospital and Children's Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Dworzak
authors.affiliation: Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Pediatric Hematology/Oncology, Zürich, University of Zurich, Switzerland.
authors.forename: J-P
authors.initials: JP
authors.lastname: Bourquin
authors.affiliation: Department of Pediatrics, Jena University Hospital, Jena, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Gruhn
authors.affiliation: Paediatric Hematology and Oncology, Medical Center, University of Essen, Essen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Fleischhack
authors.affiliation: Paediatric Haematology and Oncology, Children's Hospital Medical Center, Homburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Graf
authors.affiliation: Pediatric Hematology, Oncology and Hemostaseology, University Children's Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.affiliation: Paediatric Hematology and Oncology, Medical Center, University of Essen, Essen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kremens
authors.affiliation: Pediatric Hematology, Oncology and Hemostaseology, University Children's Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Lehrnbecher
authors.affiliation: Paediatric Hematology and Oncology, Medical Center, University of Essen, Essen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: von Neuhoff
authors.affiliation: Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: von Stackelberg
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Stray
authors.affiliation: Paediatric Hematology and Oncology, Medical Center, University of Essen, Essen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D017338:Cladribine / Q000008:administration & dosage* / Q000009:adverse effects*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate
chemical_list: D003561:Cytarabine; D017338:Cladribine; D015255:Idarubicin