Long-term remissions with weekly chlorambucil therapy in patients with intermediate-risk chronic lymphocytic leukaemia.

Abstract

Chlorambucil (Chl) has a proven and well-accepted track record in the treatment of patients with advanced or progressive chronic lymphocytic leukaemia (CLL), albeit only as palliative therapy. Chl is currently recommended as first-line therapy for elderly patients with poor performance status or patients who do not tolerate fludarabine: the preferred first-line option (Kalil & Cheson, 2000). However, there is little information in the literature on the use of Chl as maintenance therapy in patients who show a good response to initial treatment with Chl. This report describes 21 patients (13 men, 8 women; age 50–94 years, median 73 years) with intermediate-risk CLL (modified Rai Stage II or Binet Stage B) who were treated with Chl for one or more indications (Table I), according to the National Cancer Institute guidelines (Cheson et al, 1996), and were kept on long-term maintenance therapy. Initial treatment comprised Chl 0·06 mg–0·08 mg/kg daily for 2 to 4 months. Following documentation of a good clinical response (resolution of clinical symptoms/signs, normal blood counts), the frequency of therapy was reduced to 2 consecutive days each week for 4–6 months and then to once weekly. The latter was continued indefinitely or ceased if there was evidence of disease progression. Thirteen patients have remained in complete remission without lymphocytosis in the peripheral blood for 7+ to 148+ months (median 48 months); all are alive. Six patients achieved remission but had slight/stable lymphocytosis (6–12 × 109/l); four are alive at 8, 12, 13 and 67 months respectively; two patients have died as a result of unrelated causes at 18 months (road accident) and at 102 months (cardiac failure) respectively. Two patients who showed a good response initially developed progressive disease at 9 months and 3 years, respectively, and are currently on combination chemotherapy. There have been no adverse side-effects attributable to Chl therapy. Weekly maintenance therapy with Chl appears to sustain remission status in the majority of patients with initial Chl-sensitive intermediate-risk CLL; an observation which should be seen in light of the following facts: CLL is an incurable disease, predominantly afflicting the elderly (Kalil & Cheson, 2000) While fludarabine, given as initial treatment, can achieve higher responses and longer duration of remission than Chl, it has not been shown to improve the overall survival (Rai et al, 2000) Weekly maintenance therapy with Chl is simple and inexpensive