Prevention of Resistance

Since nearly all patients with chronic phase CML have persistent disease as indicated by the presence of BCR-ABL transcripts (51), it is critical to maintain sufficient BCR-ABL kinase inhibition in order to reduce the risk of disease progression or development of resistant disease. Moreover, the IRIS trial has shown that newly diagnosed CML chronic phase patients who received imatinib as their initial therapy had superior cytogenetic response and overall survival than patients who first received interferon and later on crossed over to imatinib (14). Therefore, it is recommended to initiate treatment immediately after diagnosis with 400 mg per day in chronic phases and 600 mg in advanced phases. It is important to avoid unnecessary dose reductions or interruptions. Whenever possible, imatinib side effects should be treated without dose reduction. If a dose reduction is inevitable, doses lower than 300 mg per day should be avoided. Below a daily dose of 300 mg, imatinib plasma levels are not sufficient to suppress BCR-ABL kinase activity (52), which in turn may lead to the selection of resistant subclones.

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