title: Managing Philadelphia chromosome-positive acute lymphoblastic leukemia: role of tyrosine kinase inhibitors.
abstract: Before the introduction of tyrosine kinase inhibitors, the prognosis for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia was poor. The treatment of choice, stem cell transplantation, is a potentially curative option, but it is available only for a minority of patients and is associated with significant risk of morbidity and mortality. Although imatinib is largely effective, a substantial proportion of patients become resistant or intolerant to it. The activity of imatinib may be enhanced by coadministration with chemotherapy; such treatment is effective in many patients. Dasatinib is established as a second-line treatment in patients with resistance to or intolerance of imatinib. Recent data suggest that dasatinib, either alone or in combination with chemotherapy, has utility as first-line therapy. Dasatinib is more potent than imatinib, is less susceptible to drug-resistance mechanisms, and has been shown to penetrate the blood-brain barrier, making it potentially effective for treating central nervous system disease. Patients who relapse during treatment with dasatinib frequently carry the T315I mutation of BCR-ABL. Future regimens combining dasatinib with an agent able to inhibit this mutation may further improve outcome.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA. fravandi@mdanderson.org
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D000069439:Dasatinib; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib