Safety and Tolerability

Imatinib has generally been well tolerated, with grade 3 or 4 nonhematologic toxicities being uncommon. The most common grade 1 or 2 toxicities include fluid retention, nausea, muscle cramps, skin rashes, fatigue, and diarrhea. Myelosuppression is more common in advanced phase patients than in chronic phase patients, and imatinib induced prolonged aplasia in 1% of blast crisis patients (Sawyers et al. 2002). In contrast, patients with GIST treated with 400 or 600 mg per day of imatinib had rates of grade 3/4 neutropenia and thrombocytopenia of 5% and less than 1%, respectively, demonstrating the specificity of this side effect to leukemia patients (Demetri et al. 2002). Thus, myelosuppression is more likely to be due to suppression of the BCR-ABL-positive clone as opposed to inhibition of normal hematopoiesis. For this reason, it is not clear how much is accomplished by dose reduction for myelosuppression.

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