title: Impact of residual normal metaphases in core binding factor acute myeloid leukemia.
abstract: BACKGROUND
  Karyotype allows for stratification of outcomes in acute myeloid leukemia (AML) patients. Previous data suggested that the presence of residual normal cells improved the prognosis in patients with monosomy 7. The Southwest Oncology Group (SWOG) reported the impact of residual normal metaphases in AML patients with monosomal karyotype (MK) and found a similar relationship. We determined the influence of residual normal metaphases in patients with core binding factor (CBF) AML.
  
  
  METHODS
  The presence and total number of normal and abnormal metaphases were tallied for patients with CBF AML treated in 10 consecutive SWOG trials and used as a variable to determine the effect on complete remission, refractory disease, and overall survival (OS) rates.
  
  
  RESULTS
  Among 113 CBF AML patients, median age of diagnosis was 45 years (range, 18-77 years), and median OS was 4 years (CI-2 years-not reached). Patients with inv(16) and no normal metaphases had improved OS compared with those with 1+ normal metaphases (P = .00005), whereas no difference was noted for patients with t(8;21). Multivariate analysis demonstrated that having cells with a normal karyotype had a negative impact on survival (HR, 2.11; 95% CI, 1.09-4.08; P = .026). This shorter survival was a consequence of a higher rate of refractory disease in older patients (OR, 1.03; 95% CI, 0.9998-1.06; P = .05) and in those with normal metaphases (HR, 1.26 95% CI, 1.04-1.51; P = .02).
  
  
  CONCLUSIONS
  In patients with CBF AML, the presence of cells with normal metaphases and increasing age negatively affect the prognosis, especially in patients with inv(16).
authors.affiliation: Stanford University School of Medicine, Stanford, CA 94305, USA. bruno.medeiros@stanford.edu
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Medeiros
authors.forename: Megan
authors.initials: M
authors.lastname: Othus
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D050660:Core Binding Factors / Q000235:genetics*; D005260:Female; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
chemical_list: D050660:Core Binding Factors