title: [A study to determine the safety and efficacy of imatinib mesylate in patients with chronic phase of chronic myeloid leukemia after interferon therapy failure. Four year follow-up].
abstract: Targeted therapy with the use of imatinib mesylate is a recognized option for patients with chronic myeloid leukemia (CML) not eligible for allogeneic hematopoietic cell transplantation. We present results of a multicenter phase II study on the use of imatinib in chronic phase after failure to interferon-alpha (IFN-alpha). Sixty patients (27 female, 33 male), median age 46 (range, 21-64), were included with hematologic relapse (n= 11), hematologic refractoriness (n=4), cytogenetic relapse/ /+65resistance (n=40) or intolerance to IFN-alpha (n=5). The median time from CML diagnosis was 39 months (range, 4-132), the median time of IFN-alpha therapy equaled 23 months (range, 1-78). Imatinib mesylate was administered at a dose of 400 mg/day for 1 year. In patients who achieved major cytogenetic response (MCR) the therapy was continued until progression. Thirty-three (55%) patients achieved MCR after one year of treatment. At 4 years the cumulative incidence of complete cytogenetic response equaled 40% (95% CI, 29-56). Among 27 patients who did not achieve MCR at 12 moths, in 12 cases the study course was discontinued prematurely because of blast crisis (n=9), prolonged neutropenia (n=l), severe transaminases elevation (n=l) or incidental death not related to the study drug or disease (n=l). The probability of OS at 4 years equaled 82% (95% CI, 72-91) and was lower for patients with the disease duration >36 months and those with Sokal index > or =0.8. Among patients who achieved MCR, the probability of progression-free survival was 78% (95% CI, 69-85). Time to progression (cytogenetic, n=6; blast crisis, n=l) varied from 3-36 months.
  
  
  CONCLUSIONS
  Imatinib mesylate is characterized by good tolerance and allows achieving cytogenetic response in more than half of late chronic phase CML patients with failure of interferon therapy. However, the progression rate is substantial, which raises concern regarding the curative potential of monotherapy with imatinib in this group of patients.
authors.affiliation: Katedra i Klinika Hematologii i Transplantacji Szpiku Slaskiej Akademii Medycznej, Katowicach.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Hołowiecki
authors.forename: Lech
authors.initials: L
authors.lastname: Konopka
authors.forename: Grazyna
authors.initials: G
authors.lastname: Bober
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.forename: Bernadeta
authors.initials: B
authors.lastname: Ceglarek
authors.forename: Kinga
authors.initials: K
authors.lastname: Kos
authors.forename: Beata
authors.initials: B
authors.lastname: Stella-Hołowiecka
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kruzel
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kopera
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bartkowska-Chrobok
authors.forename: Ewa
authors.initials: E
authors.lastname: Pszenna
authors.forename: Anna
authors.initials: A
authors.lastname: Sikorska
authors.forename: Barbara
authors.initials: B
authors.lastname: Pieńikowska-Grela
mesh_terms: D000328:Adult; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects*; D012074:Remission Induction / Q000379:methods; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate