ABSTRACT

Since the introduction of imatinib mesylate, the ‘first generation ’ tyrosine kinase inhibitor (TKI), into the clinic in 1998, the drug has become the preferred treatment for the majority, if not all, newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase (CP), except perhaps for children. 1 , 2 Imatinib reduces substantially the number of CML cells in a patient ’ s body, resulting in a complete cytogenetic remission in a significant proportion of patients but complete molecular responses only in a minority and then only after some years of treatment and probably in less than 50 % of patients. 3 The next (second) generation TKIs, dasa tinib and nilotinib, appear to be more potent than imatinib and are now in the clinic, for the treatment of imatinib-resistant/refractory CML and Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). 4,5 Other candidate drugs include bosutinib (SKI-606), INNO-406 (NS-187), and an aurora kinase inhibitor, MK-0457 (VX680). Allogeneic stem cell transplantation (alloSCT), however, remains the only therapeutic modality that can clearly produce long-term complete molecular remission associated, presumably, with eradication of all residual leukemia stem cells. 6,7 In this chapter we address the current treatment algorithms for patients with CML, with an emphasis on the non-transplant therapies, and speculate on some of the challenges for the future. AlloSCT is discussed in Chapter 7.