title: Result of high-dose imatinib mesylate in patients with Philadelphia chromosome-positive chronic myeloid leukemia after failure of interferon-alpha.
abstract: Imatinib at 400 mg daily is effective in chronic-phase chronic myeloid leukemia (CML) after interferon failure, although only a few patients achieve a molecular remission. We investigated whether higher doses of imatinib may be more effective. Thirty-six patients with chronic-phase CML after failure on interferon-alpha were treated with 400 mg imatinib twice daily. Median time from diagnosis was 25 months (range, 10-135 months); 4 patients (11%) had clonal evolution. All 11 patients with active disease achieved complete hematologic response. Excluding patients with fewer than 35% Ph-positive metaphases before the start of therapy, 19 (90%) of 21 evaluable patients achieved a major cytogenetic response. Of 27 evaluable patients, 24 (89%) achieved a complete cytogenetic response. Quantitative polymerase chain reaction was performed in bone marrow every 3 months. Of 32 evaluable patients, 18 (56%) showed BCR-ABL/ABL percentage ratios lower than 0.045%, including 13 (41%) with undetectable levels. With a median follow-up of 15 months, all patients were alive in chronic phase. Toxicities were similar to those reported with standard dose; 71% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induces complete cytogenetic responses in most patients with chronic-phase CML after interferon failure. This is accompanied by a high rate of molecular remission.
authors.affiliation: Department of Leukemia and Bioimmunotherapy, M. D. Anderson Cancer Center, University of Texas-Houston, 1515 Holcombe Blvd, Box 428, Houston, TX 77030, USA. jcortes@mdanderson.org
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Emil J
authors.initials: EJ
authors.lastname: Freireich
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides; D020732:Cytogenetic Analysis; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000633:toxicity; D011743:Pyrimidines / Q000008:administration & dosage* / Q000633:toxicity; D012334:RNA, Neoplasm / Q000032:analysis; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016879:Salvage Therapy
chemical_list: D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D012334:RNA, Neoplasm; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl