Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has been associated with the worst patient survival rates of the various acute leukemias. Imatinib mesylate is a novel therapeutic agent that targets the BCR-ABL tyrosine kinase, the molecular abnormality associated with Ph+ ALL. The combination of imatinib with chemotherapy has led to improved and durable treatment responses in adult patients with Ph+ ALL, including the elderly population. Hematopoietic stem cell transplantation has also integrated imatinib into its transplant strategies, with early data suggesting improved progression-free survival without clearly identifiable augmented toxicity. Second-generation tyrosine kinase inhibitors offer potentially even greater improvements on these excellent imatinib-associated outcomes. This review addresses the evolution of the management of Ph+ ALL and is intended to assist in the description of its new natural history.
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