High-dose Chlorambucil Research Articles

High-dose pulse chlorambucil: effective therapy for rapid remission induction in nodular lymphocytic poorly differentiated lymphoma.

Eighteen patients with Stage III or IV nodular poorly differentiated lymphocytic lymphoma (malignant lymphoma, infiltrative nodular type, with predominately small cleaved cells) were treated with intermittent high-dose oral chlorambucil (16 mg/m2 daily for five consecutive days each month) for one year. Complete clinical remissions occurred in 78% of these patients and partial remissions in another 17%. Complete remission usually occurred within three months of beginning therapy and with a medial follow-up of 35 months no patient has relapsed. Toxicity, usually hematologic and occurring late in therapy, has been mild, necessitating termination of therapy in only one patient. Review of recent therapy fails to demonstrate a definite long-term advantage of more aggressive treatment regimens. Intermittent high-dose chlorambucil should be further evaluated as therapy for nodular poorly differentiated lymphocytic lymphoma.

LONG-TERM EVALUATION OF CHLORAMBUCIL, INCLUDING EFFECTS OF DOSE, IN FREQUENTLY RELAPSING NEPHROTIC SYNDROME

The course of 50 patients (34 male, 16 female) who received 56 courses of chlorambucil together with prednisone (1.5-2mg/kg/d) for steroid responsive but frequently relapsing or steroid dependent nephrotic syndrome has been evaluated over a period of 0.3-15 yrs (mean 3.2 yrs). All but 2 (both < 4 yrs old at time of therapy) had remissions lasting longer than that induced by steroids alone. Only 8 patients experienced a relapse 0.3-5 yrs after this therapy, 6 of whom had disease < 3 yrs at the time of treatment. Of 6 who received second courses of chlorambucil, 5 responded with remissions currently lasting 0.3->5 yrs; one failed to respond to both high dose courses. Life table analysis shows the chlorambucil response to be more permanent than that reported with cyclophosphamide. Actuarial analysis of two dose schedules of chlorambucil (< 0.3mg/kg/d or < 14mg/kg total dose vs. > 0.3 mgAg/d or > 14mg/kg total dose) shows low dose treatment to be as effective as higher doses; at 5 yrs, 85% of low dose and 77% of high dose patients were still in remission. Immediate side effects were not dose related and included herpes zoster (3), seizures (2), and gastric symptoms (2). The results suggest: 1) continual use of high dose chlorambucil is unwarranted; 2) in terms of immediate response, immediate toxicity and long-term effect, chlorambucil has advantages over cyclophosphamide.