New modalities of therapy in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most cormmon form of leukemia in adults in Western countries. After several decades of relative inactivity, important progress has been made in our understanding of the biology and immunology of this disorder. In addition, exciting therapeutic results have been achieved with several new, unique, and effective therapies. The most interesting chemotherapeutic agent is fludarabine, a purine analogue which achieves complete remission in 13% of relapsed or refractory patients and in greater than 30% of previously untreated patients; the overall response rates of 60% and 75%, respectively, are superior to reports with other single agents or combination regimens. Related drugs with promising activity are 2'-deoxycoformycin, and 2-chlorodeoxyadenosine. Preliminary studies are evaluating allogeneic and autologous bone marrow transplantation as potentially curative therapy. Biological approaches exploiting new insights into the immunology of CLL include the use of lymphoid growth factors. Interpretation of results of CLL studies has suffered from variability in eligibility and response criteria, especially definitions of complete remission. Recently published standardized guidelines for CLL clinical trials will facilitate comparisons among therapies and help identify those which are most promising. Continued progress will require integration of laboratory science and clinical investigation.