title: Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial.
abstract: The objective of the AML HD93 treatment trial was to evaluate the outcome in young adults with acute myeloid leukemia (AML) after postremission therapy was stratified according to cytogenetically defined risk. The rationales for the study design were based (i) on previous favorable results with high-dose cytarabine in AML with t(8;21), inv/t(16q22) and in AML with normal karyotype, and ii) on encouraging results obtained in several phase II trials using autologous stem cell transplantation (SCT). Between July 1993 and January 1998, 223 eligible patients, 16-60 years of age with newly diagnosed AML other than French-American-British type M3/M3v, were entered into the trial. Risk groups were defined as follows: low risk: t(8;21) or inv/t(16q22); intermediate risk: normal karyotype; high risk: all other chromosomal abnormalities. Following intensive double induction therapy with idarubicin, cytarabine and etoposide, all patients in complete remission (CR) received a first consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). A second consolidation therapy was stratified according to the risk group: low risk: HAM; intermediate risk: related allogeneic SCT or sequential HAM; high risk: related allogeneic or autologous SCT. Double induction therapy resulted in a high CR rate of 74.5%, and 90% of the responding patients were eligible for consolidation therapy. Survival for all 223 trial entrants was 40%, and for the 166 patients who entered CR, disease-free (DFS) and overall survival were 40 and 51% after 5 years, respectively. Within the low-, intermediate- and high-risk groups, DFS and survival after 5 years were 62.5 and 87, 40 and 49 and 17 and 26% respectively, without advantage for allogeneic transplantation in the intermediate- and high-risk groups. Postremission therapy-related mortality was 0, 7 and 14%, respectively. This study demonstrates the feasibility of cytogenetically defined risk-adapted consolidation therapy. The overall trial results are at least equivalent to those of published trials supporting the risk-adapted treatment strategy.
authors.affiliation: Department of Internal Medicine III, University of Ulm, Germany.
authors.forename: R F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: A
authors.initials: A
authors.lastname: Benner
authors.forename: F
authors.initials: F
authors.lastname: Hartmann
authors.forename: F
authors.initials: F
authors.lastname: del Valle
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.forename: H
authors.initials: H
authors.lastname: Pralle
authors.forename: J Th
authors.initials: JT
authors.lastname: Fischer
authors.forename: U
authors.initials: U
authors.lastname: Gunzer
authors.forename: A
authors.initials: A
authors.lastname: Pezzutto
authors.forename: W
authors.initials: W
authors.lastname: Weber
authors.forename: W
authors.initials: W
authors.lastname: Grimminger
authors.forename: J
authors.initials: J
authors.lastname: Preiss
authors.forename: M
authors.initials: M
authors.lastname: Hensel
authors.forename: S
authors.initials: S
authors.lastname: Fröhling
authors.forename: K
authors.initials: K
authors.lastname: Döhner
authors.forename: R
authors.initials: R
authors.lastname: Haas
authors.forename: H
authors.initials: H
authors.lastname: Döhner
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000627:therapeutic use; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use; D012074:Remission Induction / Q000379:methods; D018570:Risk Assessment; D033581:Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D016019:Survival Analysis
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone