title: Acute Myeloid Leukemia (AML): different treatment strategies versus a common standard arm--combined prospective analysis by the German AML Intergroup.
abstract: OBJECTIVE
  Identifying true therapeutic progress in patients with acute myeloid leukemia (AML) requires a comparison of treatment strategies and results on the basis of uniform patient selection. To foster comparability across five clinical studies, we introduced a common standard arm combined with a general upfront randomization and performed prospective analyses with adjustment for differences in prognostic baseline characteristics.
  
  
  METHODS
  Whereas the studies' own regimens differed in chemotherapies, risk adaption, and guidelines for allogeneic stem-cell transplantation, the standard arm contained uniform cytarabine- and anthracycline-based standard-dose remission induction and high-dose consolidation courses.
  
  
  RESULTS
  Of 2,995 evaluable patients aged 16 to 60 years, 290 patients were randomly assigned to the common standard arm. Seventy percent of the 290 achieved complete remissions (62% with complete recovery, 8% with incomplete recovery; 95% CI, 65% to 76%). Five-year survival probabilities were 44.3% (95% CI, 37.7% to 50.7%) for overall survival, 44.8% (95% CI, 37.0% to 52.2%) for relapse-free survival, and 31.5% (95% CI, 25.7% to 37.4%) for event-free survival. Neither the unadjusted survival probabilities of the Kaplan-Meier method nor their adjustment for prognostic variables in multiple Cox regression models led to statistically significant different results in the three survival end points when the outcomes of each study were compared with the standard arm.
  
  
  CONCLUSIONS
  A strictly prospective comparison of different treatment strategies in patients with AML did not show clinically relevant outcome differences when compared through a common standard treatment arm. The results provide a representative basis for further therapeutic approaches.
authors.affiliation: Department of Internal Medicine A-Hematology, Oncology and Pneumology, University of Münster, Albert-Schweitzer Campus 1, Geb. A 1, 48129 Münster, Germany. buechnr@uni-muenster.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Büchner
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: Markus
authors.initials: M
authors.lastname: Schaich
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Rainer
authors.initials: R
authors.lastname: Krahl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heil
authors.forename: Utz
authors.initials: U
authors.lastname: Krug
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Sauerland
authors.forename: Achim
authors.initials: A
authors.lastname: Heinecke
authors.forename: Daniela
authors.initials: D
authors.lastname: Späth
authors.forename: Michael
authors.initials: M
authors.lastname: Kramer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Scholl
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
authors.forename: Joerg
authors.initials: J
authors.lastname: Hasford
authors.forename: Verena S
authors.initials: VS
authors.lastname: Hoffmann
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Dietger W
authors.initials: DW
authors.lastname: Niederwieser
authors.forename: Markus
authors.initials: M
authors.lastname: Pfirrmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016001:Confidence Intervals; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005858:Germany; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003561:Cytarabine; D003630:Daunorubicin