Dose modification of imatinib by monitoring the level of BCR-ABL transcript in chronic myelogenous leukemia.
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.
Ishikawa
Izumi
I
Department of Internal Medicine, Osaki Citizen Hospital, Osaki, Japan. idumi000@hotmail.com
Kato
Chiaki
C
Harigae
Hideo
H
Sugawara
Tomohiro
T
Tomiya
Yasuo
Y
Yamada
Minami
M
Ishizawa
Kenichi
K
Kameoka
Junichi
J
Miyamura
Koichi
K
Sasaki
Takeshi
T
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
D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl