Several tyrosine kinase inhibitors have activity in Ph-positive chronic and acute leukemia, but resistant disease and unacceptable side effects may limit efficacy. Ponatinib showed a high level of activity in a phase 2 study of tyrosine kinase inhibitor–resistant disease but was associated with arterial thrombosis. Patients with newly diagnosed chronic myeloid leukemia (CML) frequently receive imatinib. Although initial response rates are high, imatinib fails in up to 40% of patients because of disease resistance, frequently because of BCR-ABL kinase domain mutations or unacceptable side effects. 1 , 2 Patients who discontinue imatinib may have a response to second-generation tyrosine kinase inhibitors. However, 37 to 52% of patients do not have a response, 3 – 8 and 23 to 26% of patients have an initial major cytogenetic response that is lost by 2 years. 3 , 9 The prognosis for these patients is very poor. With the exception of the small number . . .