ABSTRACT
Background. To determine whether chlorambucil tratment benefits patients with indolent chronic lymphocytic leukemia (CLL) , we conducted two randomized trials in 1535 patients with previously untreated stage A CLL. Methods. In the first trial, 609 patients were randomly assigned to receive either daily chlorambucil or no tratament; in the second trial, 926 patients were randomly assigned to receive either intermittent chlorambucil plus prednisone or no treatment. Median follow-up for the first and second trial exceeded 11 and 6 years, respectively. The end points were overall survival, response to treatment, and disease progression. Results. Treatment of indoletn 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 interval 0.92 to 1.41; P=0.23) in the first trial and 0.96 (95 percent confidence 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 trial, 49 percent of patients did not have progression to more advanced disease and did not need therapy after follow-up of more than 11 years; however, 27 percent of patients with staage A CLL died of causes related to the disease. Conclusions. Chlorambucil does not prolong survival in patients with stage A CLL. Since deferring therapy until the disease progresses to stage B or C does not compromise survival, treatment of indolent CLL is unnecessary