Modern concepts in the treatment of chronic lymphocytic leukemia

There has been considerable progress in the treatment of chronic lymphocytic leukemia (CLL) during last 10 years. Purine analogs and monoclonal antibodies have enabled the shift from purely palliative treatment to intensive regimens aiming at complete remissions and possible prolongation of survival. Many patients have now been shown to achieve molecular responses in addition to their hematological remission. Despite this success, virtually all patients with CLL will eventually relapse and will become refractory to treatment. Allogeneic stem cell transplantation offers a chance of definite cure but is feasible in a minority of patients only. Therefore, considerable effort has been devoted to the further development of more conventional CLL management that is applicable to patient population generally affected by the disease. Emerging treatment concepts include novel combination of well-know agents such as rituximab and chlorambucil, fludarabine, cyclophosphamide and alemtuzumab, FCR with mitoxantrone amongst many. Consolidation regimens using mainly alemtuzumab are also increasingly used but are associated with a major increase in severe infections. High-dose steroids in combination with rituximab or alemtuzumab represent a promising option for refractory patients. Modern chemoimmunotherapy with the FCR regimen has also been tested in early stage patients with unfavourable prognostic factors. Finally, a there are a wide variety of novel drugs including bendamustine, a unique cytostatic with combined properties of an alkylating agent and purine analog, the monoclonal antibodies anti-CD20 ofatumumab and the anti-CD23 lumiliximab, thalidomide and its analog lenalidomide, the semi-synthetic flavonoid flavopiridol and other agents which are currently undergoing clinical trials with promising results. This article reviews the recent advances and future possibilities in the treatment of CLL.