Refractory chronic lymphocytic leukemia: Prognosis and treatment options

Chronic lymphocytic leukemia (CLL) is a common malignancy often managed by the practicing oncologist rather than at a tertiary referral center. Since no standard treatment has been shown to be curative, patients are frequently observed without treatment for many years. In the past, first-line therapy with an alkylating agent, particularly chlorambucil, was standard when treatment became necessary. Because of its superior activity in achieving remission and extending the time to relapse and disease progression compared with alkylating agents, the purine nucleoside analog fludarabine is now commonly used as first-line treatment. Historically, salvage treatment with combination chemotherapy included an alkylating agent, anthracycline, vinca alkyloid, and/or corticosteroid. Currently, salvage regimens often incorporate a purine nucleoside analog and an alkylating agent. Two monoclonal antibodies, rituximab and alemtuzumab, have become available and have made further advances in both first-line and salvage treatment of patients with CLL. In this article we review the agents and regimens that have been studied as salvage treatment of CLL. With the development of purine nucleoside analogs and monoclonal antibodies, incremental progress has been made in the therapy of previously treated patients with CLL. Newer strategies will aim to further improve the complete remission rate, which may have a positive impact on survival.