title: Chronic myeloid leukemia in chronic phase responding to imatinib: the occurrence of additional cytogenetic abnormalities predicts disease progression.
abstract: OBJECTIVE
  The acquisition of additional cytogenetic changes (clonal evolution, CE) during treatment of chronic myeloid leukemia (CML) with imatinib mesylate is currently regarded as an index of increasing resistance to imatinib. Therefore, to investigate whether CE as an isolated event increases the risk of disease progression during imatinib treatment, we compared the outcome of patients with CML in chronic phase (CML-CP) who developed CE whilst in complete hematologic remission with the outcome of comparable patients in complete hematologic remission who showed no evidence of CE.
  
  
  METHODS
  We serially studied cytogenetic findings in 102 patients receiving the Abl-tyrosine kinase inhibitor, imatinib mesylate, as sole agent to treat CML-CP who had no evidence of CE before initiation of imatinib treatment.
  
  
  RESULTS
  CE was identified during treatment with imatinib in 15 patients, 10 of whom were in complete hematologic remission. In most cases these changes occurred exclusively in the Ph+ population but in three patients additional changes occurred in a co-existing Ph-negative population. Patients with de novo CE in the absence of any other sign of disease progression had a significantly higher incidence of progression by 18 months than did non-CE patients (progression-free survival 34.3% (CI 10.5-69.8%) vs. 94.1% (CI 80.6-98.4%), p<0.0001).
  
  
  CONCLUSIONS
  Based on this relatively small series of patients, we conclude that acquisition of clonal evolution increases the risk of subsequent disease progression also in CML patients in complete hematologic remission on imatinib.
authors.affiliation: Department of Hematology, Imperial College at Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Marktel
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.forename: Nicola
authors.initials: N
authors.lastname: Foot
authors.forename: Richard
authors.initials: R
authors.lastname: Szydlo
authors.forename: Marco
authors.initials: M
authors.lastname: Bua
authors.forename: Anastasios
authors.initials: A
authors.lastname: Karadimitris
authors.forename: Valeria A S
authors.initials: VA
authors.lastname: De Melo
authors.forename: Paul
authors.initials: P
authors.lastname: Kotzampaltiris
authors.forename: Francesco
authors.initials: F
authors.lastname: Dazzi
authors.forename: Amin
authors.initials: A
authors.lastname: Rahemtulla
authors.forename: Eduardo
authors.initials: E
authors.lastname: Olavarria
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides; D002869:Chromosome Aberrations; D002999:Clone Cells / Q000473:pathology; D020732:Cytogenetic Analysis; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl