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

Follicular small cell and follicular mixed small and large cell lymphoma (F L) are incurable with conventional chemotherapy, and generally follow a rel apsing course. eventually becoming resistant to first-line therapy with alk ylating agents. Fludarabine is a novel chemotherapeutic agent that is effec tive in FL, hut 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. Resist ance was defined as failure to achieve a partial response, progression whil e on therapy, or relapse within six months of completing therapy. Seventeen patients met the criteria of alkylator-resistant FL and were included in t he 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 respons e rate of 53%. Median progression-free survival was 5.4 months and median o verall survival was 15.4 months fur all patients. Four patients underwent s ubsequent autologous stem cell transplantation: all required additional sal vage chemotherapy for post-fludarabine relapses. Three patients remain in r emission more than 12 months post-transplantation. Fludarabine produces par tial responses in patients with advanced refractory FL; however, the durati on of the response limits its utility in alkylator-resistant disease.