Combination of fludarabine and mitoxantrone in low grade, predominantly Follicular NHL: results of phase II studies in relapsed or refractory patients Fludarabine is expected to potentiate other agents through inhibition of DNA polymerase alpha and DNA ligase and its consequent interference with the DNA repair process. The addition of mitoxantrone increases the cytotoxic effect of fludarabine in vitro. McLaughlin et al developed a combination of fludarabine, mitoxantrone and dexamethasone (FND), which was very effective in 51 patients with recurrent low-grade lymphoma (including 65% FL), with an overall response rate of 94% (47% complete response (CR) rate. The median duration of response in this phase II study was 21 months for CR patients but only 9 months for partial responders (PR) patients. The median survival and failure-free survival times from the time of entry onto the FND study were 34 and 14 months, respectively. Most major responses were evident after two to four courses of chemotherapy. The need for continuation of therapy beyond attainment of remission is suggested by early relapses among patients who had early discontinuation of therapy. The predominant toxic effects were myelosuppression and infections: neutropenia < 500/µl in 20 % of courses, thrombopenia < 50000/µl in 8 % of courses and infections in 12 % of courses. Non-hematological toxicity was modest.