Outcome of induction and postremission therapy in younger adults with acute myeloid leukemia with normal karyotype: a cancer and leukemia group B study

J Clin Oncol. 2005 Jan 20;23(3):482-93. doi: 10.1200/JCO.2005.06.090. Epub 2004 Nov 8.

Abstract

Purpose: Evaluate the outcome of induction and postremission therapy in adults younger than 60 years with normal cytogenetics acute myeloid leukemia (AML).

Patients and methods: In 490 patients, induction included cytarabine and daunorubicin (AD) or cytarabine and escalated doses of daunorubicin and etoposide +/- PSC-833 (ADE/ADEP). Intensification included one cycle of high-dose cytarabine (HDAC) followed by etoposide/cyclophosphamide and mitoxantrone/diaziquone (group I), three HDAC cycles (group II), four intermediate-dose cytarabine (IDAC) or HDAC cycles (group III), or one HDAC/etoposide cycle and autologous stem-cell transplantation (ASCT; group IV).

Results: Of 350 patients receiving AD, 73% achieved complete remission (CR), compared with 82% of 140 receiving ADE/ADEP (P = .04). Splenomegaly was associated with a lower CR rate (P < .001), and ADE/ADEP, with a higher CR rate in younger patients (P = .005). The 5-year disease-free survival (DFS) rate was 28% each for intensification groups I and II, compared with 41% and 45% for groups III and IV, respectively (P = .02). The 5-year cumulative incidence of relapse (CIR) was 62% and 67% for groups I and II, respectively, compared with 54% and 44% for groups III and IV, respectively (P = .049). The type of postremission intensification remained significant for DFS and CIR in multivariable analysis.

Conclusion: In younger adults with normal cytogenetics AML, splenomegaly predicts a lower CR rate, and the postremission strategies of either four cycles of I/HDAC or one cycle of HDAC/etoposide followed by ASCT are associated with improved DFS and reduced relapse compared with therapies that include fewer cycles of cytarabine or no transplantation.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Age Factors
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aziridines / administration & dosage
  • Benzoquinones / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Karyotyping
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / pathology
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Prognosis
  • Recurrence
  • Splenomegaly*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Aziridines
  • Benzoquinones
  • Cytarabine
  • Etoposide
  • Cyclophosphamide
  • Mitoxantrone
  • diaziquone
  • Daunorubicin

Supplementary concepts

  • DAV regimen