title: Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia.
abstract: BACKGROUND
  The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy.
  
  
  METHODS
  We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events.
  
  
  RESULTS
  The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events.
  
  
  CONCLUSIONS
  After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
authors.affiliation: Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. drukerb@ohsu.edu
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Stephen G
authors.initials: SG
authors.lastname: O'Brien
authors.forename: Insa
authors.initials: I
authors.lastname: Gathmann
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Norbert
authors.initials: N
authors.lastname: Gattermann
authors.forename: Michael W N
authors.initials: MW
authors.lastname: Deininger
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Janice L
authors.initials: JL
authors.lastname: Gabrilove
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Josy
authors.initials: J
authors.lastname: Reiffers
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: Timothy
authors.initials: T
authors.lastname: Hughes
authors.forename: Hermine
authors.initials: H
authors.lastname: Agis
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Gregor
authors.initials: G
authors.lastname: Verhoef
authors.forename: John
authors.initials: J
authors.lastname: Shepherd
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Johan L
authors.initials: JL
authors.lastname: Nielsen
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
authors.forename: Kerry
authors.initials: K
authors.lastname: Taylor
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Charlene
authors.initials: C
authors.lastname: So
authors.forename: Laurie
authors.initials: L
authors.lastname: Letvak
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl