title: Core binding factor acute myeloid leukemia: the impact of age, leukocyte count, molecular findings, and minimal residual disease.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.|University of Barcelona, Barcelona, Spain.
authors: Montserrat
authors: M
authors: Hoyos
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Josep F
authors: JF
authors: Nomdedeu
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Jordi
authors: J
authors: Esteve
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Rafael
authors: R
authors: Duarte
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Josep M
authors: JM
authors: Ribera
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Andreu
authors: A
authors: Llorente
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Lourdes
authors: L
authors: Escoda
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Javier
authors: J
authors: Bueno
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Mar
authors: M
authors: Tormo
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: David
authors: D
authors: Gallardo
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Maria Paz Queipo
authors: MPQ
authors: de Llano
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Josep M
authors: JM
authors: Martí
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Anna
authors: A
authors: Aventín
authors: Networking Research Center on Bioengineering Biomaterials and Nanomedicine (CIBER-BBN MICINN ISCIII), Barcelona, Spain.
authors: Ramón
authors: R
authors: Mangues
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.
authors: Salut
authors: S
authors: Brunet
authors: Spanish CETLAM Group Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona Spanish Cancer Network (RTICC), Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.|Banc de Sang i Teixits de Catalunya, Barcelona, Spain.
authors: Jorge
authors: J
authors: Sierra
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D050660:Core Binding Factors / Q000235:genetics*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D000075142:RUNX1 Translocation Partner 1 Protein; D012008:Recurrence; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C107844:AML1-ETO fusion protein, human; C095514:CBFbeta-MYH11 fusion protein; D050676:Core Binding Factor Alpha 2 Subunit; D050660:Core Binding Factors; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein
keywords: acute myeloid leukemia; biologic and molecular prognostic factors; core binding factors
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