title: A population study showing that the advent of second generation tyrosine kinase inhibitors has improved progression-free survival in chronic myeloid leukaemia.
abstract: BACKGROUND
  Population based data suggest the proportion of patients failing imatinib in chronic myeloid leukaemia (CML) is higher than the reported one-third of patients in clinical trials. Clinical trials have demonstrated second generation tyrosine kinase inhibitors (TKI) dasatinib and nilotinib can restore complete cytogenetic remission (CCR) and major molecular response (MMR) to many patients failing imatinib, but their impact in the general population is not clear.
  
  
  METHODS
  We report CML outcome in a population of 2.3 million people in a geographically contiguous area of North West England and North Wales.
  
  
  RESULTS
  Between 2003 and 2009, 192 new CML cases were diagnosed, of whom 184 were in chronic phase and 160 started on imatinib. The maximal CCR rate was 65% at 24 months and the maximal MMR rate was 50% at 36 months. Patients diagnosed since second generation TKI became available for imatinib failure had a more rapid cumulative CCR and MMR rate and a significantly improved progression free survival (p=0.022) than those diagnosed before this time.
  
  
  CONCLUSIONS
  The study indicates that second generation TKI have improved CML outcome in the general population.
authors.affiliation: Haematology Department, Royal Liverpool University Hospital, Liverpool, UK. Sebastian.Francis@liv.ac.uk
authors.forename: Sebastian
authors.initials: S
authors.lastname: Francis
authors.forename: Claire
authors.initials: C
authors.lastname: Lucas
authors.forename: Steven
authors.initials: S
authors.lastname: Lane
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.forename: Sarah
authors.initials: S
authors.lastname: Watmough
authors.forename: Katy
authors.initials: K
authors.lastname: Knight
authors.forename: Jo
authors.initials: J
authors.lastname: Bell
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kaleel-Rahman
authors.forename: Edwin
authors.initials: E
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: O'Brien
authors.forename: Nauman M
authors.initials: NM
authors.lastname: Butt
authors.forename: Walid
authors.initials: W
authors.lastname: Sadik
authors.forename: Lally
authors.initials: L
authors.lastname: De Soysa
authors.forename: Jim R C
authors.initials: JR
authors.lastname: Seale
authors.forename: Rahuman
authors.initials: R
authors.lastname: Salim
authors.forename: Richard E
authors.initials: RE
authors.lastname: Clark
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage; D000069439:Dasatinib; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D013844:Thiazoles / Q000008:administration & dosage; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib