Pharmacotherapeutic advances in the treatment of acute lymphoblastic leukaemia in adults

Acute lymphoblastic leukaemia (ALL) in adults is a challenging malignancy in that many patients will show evidence of initial chemotherapy responsiveness but will subsequently relapse. The disease is heterogeneous and outcomes vary dramatically depending on the prognostic factors present in an individual patient. An important determinant of outcome is the age of the patient. The stunning success of therapy in paediatric ALL has led to the use of intensive paediatric regimens in adolescents and young adults with what appear to be improved outcomes. For patients who relapse or have high-risk features, blood and marrow transplantation (BMT) continues to play an important role in the therapeutic armamentarium. The use of reduced-intensity conditioning regimens for allogeneic BMT suggests that outcomes may be improved by this approach. Monoclonal antibodies are showing benefit as single agents in the relapsed setting or in combination with chemotherapy in newly diagnosed patients. In recent years, several new chemotherapeutic agents have shown promise as single agents and are being incorporated into multi-agent chemotherapy. The development of tyrosine kinase inhibitors for Philadelphia chromosome-positive leukaemias has significantly improved outcomes. The molecular revolution has led to the identification of new aberrant molecular pathways in the pathogenesis of ALL, and drugs targeting these aberrancies are in various stages of development preclinically and clinically. These developments bring the hope that therapeutic outcomes in adult ALL can begin to approach those seen in the paediatric setting.