Core Binding Factor Acute Myeloid Leukemia: The Impact of Age, Leukocyte Count, Molecular Findings, and Minimal Residual Disease

Eur J Haematol. 2013 Sep;91(3):209-18. doi: 10.1111/ejh.12130. Epub 2013 Jul 25.

Abstract

Purpose: Most patients with acute myeloid leukemia (AML) and genetic rearrangements involving the core binding factor (CBF) have favorable prognosis. In contrast, a minority of them still have a high risk of leukemia recurrence. This study investigated the adverse features of CBF AML that could justify investigational therapeutic approaches.

Patients and methods: One hundred and fifty patients (median age 42 yr, range 16-69) with CBF AML (RUNX1-RUNX1T1 n = 74; CBFB-MYH11 n = 76) were prospectively enrolled into two consecutive CETLAM protocols at 19 Spanish institutions. Main clinic and biologic parameters were analyzed in the whole series. In non-selected cases with available DNA samples, the impact of molecular characterization and minimal residual disease (MRD) was also studied.

Results: Overall, complete remission (CR) rate was 89% (94% in ≤50 yr old and 72% in >50 yr, P = 0.002). At 5 yr, cumulative incidence of relapse (CIR) was 26 ± 1%, disease-free survival (DFS) 62 ± 6%, and overall survival (OS) 66 ± 4%. In multivariate analyses, leukocyte count above 20 × 10(9) /L, BAALC over-expression, and high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy (CT) led to increased relapse rate. Regarding OS, age >50 yr, leukocyte count above 20 × 10(9) /L, and increased MN1 expression were adverse features.

Conclusion: Age, leukocyte counts, BAALC, and MN1 gene expressions as well as high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy are useful tools to predict the outcome and should be considered for risk-adapted therapy.

Keywords: acute myeloid leukemia; biologic and molecular prognostic factors; core binding factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factors / genetics*
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukocyte Count
  • Male
  • Middle Aged
  • Neoplasm, Residual
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • RUNX1 Translocation Partner 1 Protein
  • Recurrence
  • Translocation, Genetic
  • Young Adult

Substances

  • AML1-ETO fusion protein, human
  • CBFbeta-MYH11 fusion protein
  • Core Binding Factor Alpha 2 Subunit
  • Core Binding Factors
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein