Fludarabine in alkylator-resistant follicular non-Hodgkin's lymphoma

Follicular small cell and follicular mixed small and large cell lymphoma (FL) are incurable with conventional chemotherapy, and generally follow a relapsing course, eventually becoming resistant to first-line therapy with alkylating agents. Fludarabine is a novel chemotherapeutic agent that is effective in FL, but its role in alkylator-resistant disease remains unclear. We conducted a retrospective review of all patients with alkylator-resistant FL treated with fludarabine. Patients were identified from pharmacy records and included if they fulfilled criteria for alkylator-resistant FL. Resistance was defined as failure to achieve a partial response, progression while on therapy, or relapse within six months of completing therapy. Seventeen patients met the criteria of alkylator-resistant FL and were included in the analysis. All patients received fludarabine 25 mg/m(2) for five days. A median of 2.5 courses of fludarabine was given. One patient had a complete remission and eight patients had partial remissions, for an overall response rate of 53%. Median progression-free survival was 5.4 months and median overall survival was 15.4 months for all patients. Four patients underwent subsequent autologous stem cell transplantation; all required additional salvage chemotherapy for post-fludarabine relapses. Three patients remain in remission more than 12 months post-transplantation. Fludarabine produces partial responses in patients with advanced refractory FL; however, the duration of the response limits its utility in alkylator-resistant disease.