title: Dose modification of imatinib by monitoring the level of BCR-ABL transcript in chronic myelogenous leukemia.
abstract: Chronic myelogenous leukemia (CML) is a hematological malignancy that is characterized by the chromosome anomaly, t(9;22)(q34;q11). By this chromosomal translocation, a novel activated tyrosine kinase, BCR-ABL chimeric protein, is generated, and the protein is causative of the disease. Recently, Imatinib mesylate targeting to a BCR-ABL chimeric protein has been developed, and shown to achieve complete remission at a high rate. Patients are currently required to receive a fixed dose, 400 mg daily; however, it is possible that some of patients can maintain their remission with reduced doses of imatinib. In this study, we determined levels of BCR-ABL transcript in CML patients by real-time quantitative polymerase chain reaction analysis, and explored the possibility of individualization of therapeutic doses of imatinib. Thirty-five CML patients, including 17 newly diagnosed patients, 16 patients pre-treated with interferon-alpha, and 2 relapsed patients after allogeneic transplantation, were treated with imatinib. Complete cytogenetic response was achieved in 31 (89%) patients. Major molecular response (MMR) was achieved in 21 (60%). Complete molecular response (CMR) was achieved in 7 (20%). Imatinib was discontinued in 2 patients, one patient with MMR due to noncompliance and other patient sustaining CMR, but both patients relapsed 7 and 13 months later, respectively. The doses of imatinib were reduced in 7 patients due to its side effects, but 4 out of the 7 patients have sustained MMR, and 2 of them have sustained CMR for more than 23 months. These results indicate that some patients are able to maintain MMR with low-dose imatinib.
authors.affiliation: Department of Internal Medicine, Osaki Citizen Hospital, Osaki, Japan. idumi000@hotmail.com
authors.forename: Izumi
authors.initials: I
authors.lastname: Ishikawa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kato
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sugawara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tomiya
authors.forename: Minami
authors.initials: M
authors.lastname: Yamada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Kameoka
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000097:blood*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010347:Patient Care Planning; D010879:Piperazines / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D011743:Pyrimidines / Q000008:administration & dosage*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl