Chronic myeloid leukemia cells contain a Bcr-Abl oncoprotein with an enhanced tyrosine kinase activity, which is considered to be the principal cause of the leukemia. The use of the first-generation tyrosine kinase inhibitor imatinib to inhibit the dysregulated kinase activity has proved remarkably successful, and imatinib as a single-agent is now considered to be the best initial treatment for the majority of adult patients in chronic phase. For patients who develop resistance to imatinib, the Bcr-Abl signaling pathway is often re-activated, second generation tyrosine kinase inhibitors, such as dasatinib or nilotinib, might restore the kinase inhibition. Allogeneic stem cell transplantation is now generally offered to older patients in whom imatinib therapy, and perhaps dasatinib or nilotinib also, have failed; efforts to establish firm criteria for the selection of second-line therapies after imatinib failure continue. At this time, children and younger adults should probably be considered for transplantation as first-line treatment.
Clinical Lymphoma & Myeloma, Vol. 7, Suppl. 3, S95-S101, 2007