Novel therapeutic strategies with alemtuzumab for chronic lymphocytic leukemia

In the last 10 years purine analogs have become the chemotherapy of choice for the first-line treatment of chronic lymphocytic leukemia, principally because of their superior efficacy compared with alkylating agents. However, many patients experience a relapse after an initial response or become refractory to these agents. The introduction of immunotherapeutic agents has provided renewed hope for fludarabine-refractory patients. Several clinical trials have shown the efficacy of alemtuzumab in patients with fludarabine-refractory chronic lymphocytic leukemia, including those with poor prognostic factors. Current studies indicate that treatment with alemtuzumab can achieve remissions with undetectable residual disease, as assessed by highly sensitive methods such as quantitative polymerase chain reaction or 4-color flow cytometry. These results suggest new applications for alemtuzumab such as combination treatment with chemotherapeutics or immunotherapeutics, maintenance therapy, and in vivo bone marrow purging prior to transplantation. A number of clinical trials are under way assessing the role of alemtuzumab in these settings.