Adverse Events after Imatinib Mesylate Therapy

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Abstract
Chronic myelomonocytic leukemia and myelofibrosis with myeloid metaplasia are hematopoietic stem-cell disorders for which there is no effective drug therapy. Imatinib mesylate (Gleevec, Novartis, Basel, Switzerland), formerly known as STI571, is an orally bioavailable derivative of 2-phenylaminopyrimidine that stabilizes an inactive conformation of BCR-ABL and related kinases.1 One of these kinases is the platelet-derived growth factor receptor.2 Because the pathogenesis of both chronic myelomonocytic leukemia and myelofibrosis with myeloid metaplasia may involve signal transduction mediated by platelet-derived growth factor, we initiated two independent pilot studies of imatinib mesylate in these two disorders. We report 3 cases of splenic rupture: 2 occurred among 3 patients with chronic myelomonocytic leukemia, and 1 occurred among 23 patients with myelofibrosis with myeloid metaplasia who were enrolled in phase 2 trials that had been approved by the institutional review boards of participating institutions.