Purine nucleoside analogues and combination therapies in B-cell chronic lymphocytic leukemia: dawn of a new era

Purine nucleoside analogues are unique drugs that are effective in a variety of hematologic malignancies. Fludarabine and 2-chlorodeo-xyadenosine (2-CdA) are active in chronic lymphocytic leukemia (CLL) both as salvage therapy and in newly diagnosed patients. These agents have revolutionized therapeutic strategies for patients with CLL that had remained unchanged for many years and included alkylating agents-based therapy with no potential for long-term remission or cure. Purine analogues have also been successfully combined with a variety of other chemotherapeutic drugs such as mitoxantrone, cyclophosphamide, corticosteroids, and monoclonal antibodies, specifically Rituximab and CAMPATH-1H. These agents are immunosuppressive and have been associated with opportunistic infections, the incidence of which can be significantly reduced by early recognition and administration of prophylactic antibiotics. In this review, the activity and toxicity of 2-CdA, fludarabine, and pentostatin in CLL as single agents and in combination with conventional chemotherapy are discussed. These drugs are increasingly used as initial therapy in CLL. Such strategies are associated with higher remission rates than have been previously achieved and in some cases, molecular remission, suggesting an important step towards cure. (C) 2003 Published by Elsevier Ltd.