title: Prognostic factors in normal karyotype acute myeloid leukemia in the absence of the FLT3-ITD mutation.
abstract: Patients with normal karyotype acute myeloid leukemia (NK-AML) without the FLT3 internal tandem duplication (FLT3-ITD) mutation account for approximately 30% of all AML cases, and exhibit a heterogeneous clinical outcome. Except for NPM1 mutations, prognostic factors in this subgroup of AML are still unclear. Here we explored the impact of immunophenotypic markers along with NPM1 mutations and clinical features on the outcome of 133 FLT3-ITD negative NK-AML patients. CD34 expression was associated with poorer complete remission (CR) rate, disease-free survival (DFS), event-free survival (EFS), and overall survival (OS), whereas CD56 expression adversely affected EFS and OS. In contrast, NPM1 mutations correlated with an improved CR rate, DFS, and EFS. Moreover, males experienced shorter DFS and EFS, while older patients (≥60 years) had shorter EFS. Multivariate analysis of age, gender, NPM1, CD34, and CD56 showed NPM1 mutation was an independent predictor of better CR rate, DFS, and EFS (P<0.001, P=0.003, and P=0.006, respectively). In addition, older age was associated with shorter DFS and EFS (P=0.045 and P=0.028, respectively), and CD56 positivity predicted shorter EFS (P=0.012). Our results confirm the favorable impact of NPM1 mutations and identify the adverse prognostic relevance of CD56 expression in this subgroup of AML.
authors.affiliation: Department of Laboratory Hematology, University Health Network, Toronto, ON, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Jiang
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Joseph
authors.initials: J
authors.lastname: Brandwein
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019002:CD56 Antigen / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D020440:Gene Duplication; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D020080:Tandem Repeat Sequences / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; D019002:CD56 Antigen; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3