title: A simulation study using validated prognostic factors to assess expected long-term survival.
abstract: OBJECTIVE
  In chronic myeloid leukemia, after promising results in major cytogenetic remission (MCR), long-term survival data on imatinib treatment is of particular interest, especially in relation to former standard treatment based on interferon-alpha. However, data is still unavailable and due to high remission rates, most patients randomized to interferon-alpha in a clinical trial crossed over to imatinib. Therefore, to assess the expected long-term survival advantage with imatinib, a simulation study based on prognostic factors validated for interferon-alpha treatment was performed.
  
  
  METHODS
  In interferon-alpha-treated patients with intermediate-risk and low-risk according to the established New CML score, survival probabilities of patients with MCR were significantly higher than those of patients without MCR. Three samples with simulated survival data for imatinib-treated intermediate-risk patients were constituted by randomly drawing varying percentages of their survival times from interferon-alpha-treated intermediate-risk patients with MCR and the remaining data from intermediate-risk patients without MCR. The same procedure was applied to low-risk patients.
  
  
  RESULTS
  The 10-year survival probabilities of inter-feron-alpha-treated intermediate-risk and low-risk patients were 0.22 and 0.37. In the simulated samples, when 80%, 65%, and 50% of survival times were as favorable as for interferon-alpha-treated patients with MCR, respectively, the corresponding survival probabilities were 0.43 and 0.57, 0.36 and 0.49, and 0.30 and 0.42.
  
  
  CONCLUSIONS
  In all simulation samples, increments of survival probabilities by imatinib were predicted, although survival probabilities of patients with MCR were assumed to be lower than with interferon-alpha. Prognosticated survival advantage with imatinib is backed by increasing observation time of imatinib-treated patients in real studies.
authors.affiliation: IBE Institut für Medizinische Informatik, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität, München, Germany. pfi@ibe.med.uni-muenchen.de
authors.forename: M
authors.initials: M
authors.lastname: Pfirrmann
authors.forename: J
authors.initials: J
authors.lastname: Hasford
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D002648:Child; D003198:Computer Simulation; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007155:Immunologic Factors / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011336:Probability; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D001549:Benzamides; D007155:Immunologic Factors; D016898:Interferon-alpha; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate