The monoclonal antibodies Campath-1H and rituximab in the therapy of chronic lymphocytic leukemia

The treatment options for chronic lymphocytic leukemia (CLL) beside standar d therapy with chlorambucil or other alkylating agents have dramatically in creased in the last few yea rs. Promising results have been reported with n ew cytotoxic agents such as the purine analogues fludarabine and 2-chlordeo xy-adenosine, either at first diagnosis or at relapse. Nevertheless, all pa tients with CLL relapse after initial response. Since residual lymphoma cel ls are very likely to be the origin of the clinical relapse, there is a nee d for new therapeutic approaches with different mechanism of action to elim inate these residual cells. These approaches include allogeneic or autologo us stem cell transplantation as well as immunotherapeutic strategies. Monoc lonal antibodies, either alone or conjugated to toxins or radioisotopes, ar e thus being actively investigated. In clinical trials the genetically engi neered chimeric unconjugated anti-CD20 antibody Rituximab and the humanized unconjugated anti-CD52 antibody Campath-1H achieved the most promising res ults in the treatment of patients with relapsed or refractory low-grade non -Hodgkin's lymphoma. Thus far there is only little clinical experience with Rituximab in patients with CLL, and the exact role of these agent in the t reatment of CLL has still to be determined in ongoing and future trials. As a single agent Campath-1H showed more clinical activity in previously trea ted CLL patients than Rituximab, with response rates of up to 33% in a mult icenter pivotal study. Furthermore, the potential risks of tumor lysis and anaphylaxia for both antibodies and immunosuppression particularly for Camp ath-1H must be taken into account. The present review will compare the deve lopment and the basic principles of these unconjugated monoclonal antibodie s and consider their present and potential role in the treatment of patient s with CLL.