Practical aspects of the treatment of chronic myelogenous leukemia with imatinib mesylate

Imatinib mesylate (Gleeve; formerly known as STI-571; Novartis Pharmaceuticals, Basel, Switzerland) is a protein tyrosine kinase inhibitor that has been approved by the US Food and Drug Administration for chronic-phase chronic myeloid leukemia (CML) that is refractory to or intolerant of interferon-alpha, and with accelerated and blast-phase CML. Imatinib is remarkably effective as treatment for chronic-phase and accelerated-phase CML at doses of 400 mg and 600 mg daily, respectively. Although dramatic responses are noted in patients with myeloid blast crisis, lymphoid blast crisis, and Philadelphia chromosome-positive acute lymphoblastic leukemia, the responses are usually incomplete and of short duration. The role of imatinib in relation to allogeneic stem cell transplantation is discussed, recognizing that the data on which any decisions can be made are relatively immature. At this time, it remains to be seen whether the chronic phase of CML can be extended sufficiently long in some patients so that they are functionally "cured," and whether doses of imatinib higher than 400 mg daily will improve response rates in chronic-phase CML. The feasibility of combining imatinib with other agents also needs to be examined, as does the utility of molecular monitoring of response. Finally, developing methods to overcome resistance to imatinib is a looming challenge.