title: Prognostic impact of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia treated with nilotinib or dasatinib.
abstract: BACKGROUND
  Deletions of derivative chromosome 9 are a poor prognostic factor in patients with chronic myeloid leukemia (CML) treated with hydroxyurea, interferon, or stem cell transplantation. Imatinib may overcome the adverse prognostic impact of deletions of derivative chromosome 9.
  
  
  METHODS
  A study was undertaken to investigate the prognostic impact of deletions of derivative chromosome 9 in 353 patients with CML receiving the second generation tyrosine kinase inhibitors (TKIs) nilotinib (n = 161) or dasatinib (n = 192).
  
  
  RESULTS
  Deletion of derivative chromosome 9 status was determined in 245 (69%). Twenty-eight (11%) patients, 22 in chronic phase, 4 in accelerated phase, and 2 in blast phase, carried deletions of derivative chromosome 9, including 17 receiving nilotinib and 11 receiving dasatinib (P = .47). Overall survival (OS) at 24 months was similar between patients with or without deletions of derivative chromosome 9 (70% vs 71%, P = .76). For patients in chronic phase, no significant differences in overall major cytogenetic response (77% vs 82%, P = .57) or complete cytogenetic response (77% vs 81%, P = .71) rates were observed between patients with or without deletions of derivative chromosome 9. At 24 months, patients with CML in chronic phase without deletions of derivative chromosome 9 had improved event-free survival (EFS) (88% vs 66%, P = .07) and OS (96% vs 82%; P = .08) compared with those carrying deletions of derivative chromosome 9. However, multivariate analysis established second-line versus frontline second generation TKI therapy as the only adverse prognostic factor for EFS and increased bone marrow blast burden and older age as independent adverse prognostic factors for OS.
  
  
  CONCLUSIONS
  Deletions of derivative chromosome 9 do not appear to be an independent risk factor for survival among patients with CML in chronic phase receiving second generation TKIs.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002899:Chromosomes, Human, Pair 9; D000069439:Dasatinib; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D017384:Sequence Deletion; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib