NEW PROSPECTS IN THE TREATMENT OF INDOLENT LYMPHOMAS WITH PURINE ANALOGS

PURPOSE To review the activity of the purine analogues fludarabine, cl adribine (2-chlorodeoxyadenosine [2-CdA]), and pentostatin (2'-deoxyco formycin) in the treatment of indolent lymphoid malignancies, includin g chronic lymphocytic leukemia, hairy cell leukemia, and indolent non- Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS Patients with previou sly untreated, relapsed, or refractory indolent NHL and other indolent lymphoid malignancies who have been treated with purine analogues. RE SULTS Purine analogues have revolutionized the treatment of indolent l ymphomas. Fludarabine induces responses in almost 50% of patients with relapsed or refractory indolent NHL and produces complete remissions (CRs) in 10% to 15% of patients. In patients receiving fludarabine as initial treatment, CRs are achieved in almost 40%, with an overall res ponse rate of 70% and a median time to progression > 1 year. Response rates with 2-CdA in previously treated patients appear similar to thos e with fludarabine, although less durable. Fludarabine and 2-CdA achie ve a higher number of durable responses in Waldenstrom's macroglobulin emia than are generally achieved with alkylating agents in this diseas e. Pentostatin appears to be less active in NHL. Newer purine analogue s currently in clinical trials in lymphomas include gemcitabine and co mpound 506U. Promising activity has been reported with the combination of fludarabine, mitoxantrone, dexamethasone, and fludarabine plus cyc lophosphamide. Combinations of 2-CdA with other agents are also in dev elopment. Toxicities associated with these purine analogues primarily include moderate myelosuppression, profound immunosuppression, neuroto xicity at higher than recommended doses, and a possible increase in se condary malignancies. CONCLUSION The purine analogues should provide t he basis for new treatment strategies with the goal of curing patients with indolent NHL. For progress to continue, patients must be referre d to important and innovative clinical research trials.