title: Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group.
abstract: OBJECTIVE
  The purpose of the study was to assess the contribution of age and disease variables to the outcome of untreated patients with acute myeloid leukemia (AML) receiving varying intensive induction chemotherapy.
  
  
  METHODS
  Patients 16 to 85 years of age with primary AML, known karyotype, and uniform postremission chemotherapy enrolled onto two consecutive trials were eligible and were randomly assigned to induction either with a standard-dose (cytarabine, daunorubicin, and 6-thioguanine) and a high-dose (cytarabine and mitoxantrone) combination, or with two courses of the high-dose combination. Subgroups were defined by karyotype, nucleophosmin and FLT3 mutation, WBC count, serum lactate dehydrogenase, and residual blasts.
  
  
  RESULTS
  In 1,284 patients, the overall survival at 4 years in those younger and older than 60 years was 37% versus 16% (P < .001) and the ongoing remission duration was 46% versus 22% (P < .001). Similar age-related differences in outcome were found for all defined subgroups. No difference in outcome according to randomly assigned treatment regimen was observed in any age group or prognostic subset. Regarding prognostic subgroups, molecular factors were also considered.
  
  
  CONCLUSIONS
  Under harmonized conditions, older and younger patients with AML show modest differences in their risk profiles and equally no dose response to intensified chemotherapy. Their observed fundamental difference in outcome across all subgroups remains unexplained. Further molecular investigation may elucidate the age effect in AML and identify new targets.
authors.affiliation: University of Münster, Department of Hematology/Oncology, Münster, Germany. buechnr@uni-muenster.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Büchner
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
authors.forename: Jan
authors.initials: J
authors.lastname: Braess
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
authors.forename: Joachim
authors.initials: J
authors.lastname: Kienast
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Andreas
authors.initials: A
authors.lastname: Grüneisen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Albrecht
authors.initials: A
authors.lastname: Reichle
authors.forename: Georg
authors.initials: G
authors.lastname: Maschmeyer
authors.forename: Carlo
authors.initials: C
authors.lastname: Aul
authors.forename: Eva
authors.initials: E
authors.lastname: Lengfelder
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Sauerland
authors.forename: Achim
authors.initials: A
authors.lastname: Heinecke
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wörmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D011379:Prognosis; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3