Tohoku J. Exp. Med., 2006, 210(4)

Dose Modification of Imatinib by Monitoring the Level of BCR-ABL Transcript in Chronic Myelogenous Leukemia

IZUMI ISHIKAWA,¹ CHIAKI KATO,² HIDEO HARIGAE,³ TOMOHIRO SUGAWARA,¹ YASUO TOMIYA,³ MINAMI YAMADA,³ KENICHI ISHIZAWA,³ JUNICHI KAMEOKA,³ KOICHI MIYAMURA⁴ and TAKESHI SASAKI³

¹Department of Internal Medicine, Osaki Citizen Hospital, Osaki, Japan, ²Division of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan, ³Department of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan, ⁴Department of Internal Medicine, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

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.

keywords —— chronic myeloid leukemia; imatinib mesylate; RQ-PCR; BCR-ABL; dose modification

© 2006 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2006, 210, 355-363

Correspondence: Izumi Ishikawa, M.D., Department of Internal Medicine, Osaki Citizen Hospital, Osaki 989-6183, Japan.

e-mail: idumi000@hotmail.com