CHLORAMBUCIL IN INDOLENT CHRONIC LYMPHOCYTIC-LEUKEMIA

Background To determine whether chlorambucil treatment benefits patien ts with indolent chronic lymphocytic leukemia (CLL), we conducted two randomized trials in 1535 patients with previously untreated stage A C LL. Methods In the first trial, 609 patients were randomly assigned to receive either daily chlorambucil or no treatment; in the second tria l, 926 patients were randomly assigned to receive either intermittent chlorambucil plus prednisone or no treatment. Median follow-up for the first and second trials exceeded 11 and 6 years, respectively. The en d points were overall survival, response to treatment, and disease pro gression. Results Treatment of indolent CLL did not increase survival in either trial. In the treated group, as compared with the untreated group, the relative risk of death was 1.14 (95 percent confidence inte rval, 0.92 to 1.41; P=0.23) in the first trial and 0.96 (95 percent co nfidence interval, 0.75 to 1.23; P=0.74) in the second trial, with 76 percent and 69 percent of patients, respectively, having a response to therapy. Although chlorambucil slowed disease progression, there was no effect on overall survival. In the untreated group in the first tri al, 49 percent of patients did not have progression to more advanced d isease and did not need therapy after follow-up of more than 11 years; however, 27 percent of patients with stage A CLL died of causes relat ed to the disease. Conclusions Chlorambucil does not prolong survival in patients with stage A CLL. Since deferring therapy until the diseas e progresses to stage B or C does not compromise survival, treatment o f indolent CLL is unnecessary. (C) 1998, Massachusetts Medical Society .