title: High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia.
abstract: Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). However, most patients treated with 400 mg imatinib daily have variable levels of residual molecular disease. We treated 114 patients with newly diagnosed chronic phase CML with 400 mg imatinib twice daily. Overall, 109 patients (96%) had a major cytogenetic response (Philadelphia chromosome [Ph] < 35%), and 103 (90%) had a complete response (Ph 0%). With a median follow-up of 15 months, no patient has progressed to accelerated or blastic phase. The estimated 2-year survival rate was 94%. By quantitative polymerase chain reaction (QPCR) studies, 71 (63%) of 112 patients showed BCR-ABL/ABL percentage ratios decrease to less than 0.05%, and 31 (28%) to undetectable levels. Compared with standard-dose imatinib, high-dose imatinib was associated with significantly better complete cytogenetic response (P =.0005), major molecular response (QPRC < 0.05%; P =.00001), and complete molecular response (undetectable BCR-ABL; P =.001). High-dose imatinib was well tolerated but resulted in more frequent myelosuppression; 82% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induced higher rates of complete cytogenetic response and of molecular response in patients with newly diagnosed chronic phase CML.
authors.affiliation: Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA. hkantarj@mdanderson.org
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: Laurie
authors.initials: L
authors.lastname: Letvak
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D035703:Therapies, Investigational
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D015507:Drugs, Investigational; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate