title: Emerging therapeutic options for Philadelphia-positive acute lymphocytic leukemia.
abstract: Acute lymphocytic leukemia (ALL) is a heterogeneous group of disorders that are associated with a cure rate of > 80% in children. The prognosis in adults is considerably inferior, with age, disease bulk, leukemia karyotype and immune phenotype being prognostically relevant. Adult ALL treatment programs include induction, intensified consolidation and maintenance phases with CNS prophylaxis. The addition of imatinib in patients with BCR-ABL-positive ALL has improved the prognosis of this subgroup, but their survival is still poor. Initial data on the second-generation BCR-ABL inhibitors, dasatinib and nilotinib, indicate a potentially greater efficacy than imatinib, but the improvement is likely to be modest. The overall efforts in terms of developmental therapeutics in ALL are very modest and not in keeping with the urgent need for improvement. Most agents being investigated have mechanisms of action similar to those of existing agents for ALL therapy and thus represent modest opportunities to improve results. Of such agents, data on BCR-ABL inhibitors, sphingosomal vincristine, pemetrexed, talotrexin, annamycin and ABT-751 are reviewed.
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yesid
authors.initials: Y
authors.lastname: Alvarado
authors.forename: Effrosyni
authors.initials: E
authors.lastname: Apostolidou
authors.forename: Ronan
authors.initials: R
authors.lastname: Swords
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000627:therapeutic use; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D005971:Glutamates / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000068437:Pemetrexed; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013449:Sulfonamides / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
chemical_list: C490492:ABT751; D000970:Antineoplastic Agents; D005971:Glutamates; D013449:Sulfonamides; D000068437:Pemetrexed; D014750:Vincristine; D006147:Guanine; D004317:Doxorubicin; D016044:Fusion Proteins, bcr-abl; C080315:annamycin