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.

Keywords::

• acute lymphocytic leukemia
• BCR-ABL
• Philadelphia chromosome