Therapy of Advanced‐Stage and Resistant Chronic Myeloid Leukemia

In the developed world, 85–90% of patients with chronic myeloid leukemia are diagnosed in the chronic phase. With introduction of imatinib (IM), the treatment of chronic phase has significantly changed over the last decade. The majority of newly diagnosed patients with chronic phase chronic myeloid leukemia (CML-CP) respond well to imatinib therapy, with overall survival of over 70% of long-term recipients achieving complete cytogenetic response. However, ∼30% of newly diagnosed patients with CML-CP failed imatinib treatment during the first 5 years of therapy. Imatinib failure could be a result of imatinib resistance and/or intolerance. Therapeutic options for patients with imatinib resistance include high-dose imatinib, second-generation tyrosine kinase inhibitors (TKIs), and stem cell transplantation (SCT). Selection of second-generation TKIs (dasatinib or nilotinib) or high-dose imatinib may be guided by the presence and type of mutation, disease phase at the time of imatinib mesylate (IM) resistance, and the patient's tolerance to imatinib. Although the prognosis of patients with CML-CP has improved significantly over last decade, there has not been much improvement in the prognosis for patients with advanced-stage CML (accelerated phase and blast crisis). Some patients with advanced phase CML will respond to imatinib and second-generation TKIs. However, in most of the patients, the risk of resistance is high and the response is short lived. Hence, in many patients, allogeneic stem cell transplantation should be the preferred approach once second chronic phase has been achieved.