Purine Analogs for the Treatment of Low-Grade Lymphoproliferative Disorders

PRIMARY PURPOSE: Low-grade lymphoproliferative disorders follow an indolent clinical course but are incurable with current therapy. Recently, three active agents for the treatment of these diseases have been identified: the purine analogs fludarabine, pentostatin and 2-chlorodeoxyadenosine. The purpose of this review is to summarize the current knowledge on the mechanism of action, clinical activity and toxicities of the purine analogs. METHODS: Articles, abstracts and letters to the editor appearing in English literature and involving the use of the purine analogs in the treatment of hairy cell leukemia, chronic lymphocytic leukemia, indolent non-Hodgkin's lymphoma, cutaneous T cell lymphomas and Waldenstrom's macroglobulinemia were reviewed. RESULTS AND CONCLUSION: Purine analogs have marked cytoreductive potential in the treatment of chronic lymphocytic leukemia, indolent non-Hodgkin's lymphoma and hairy cell leukemia. Major side effects include myelosuppression and infections. Profound lymphocytopenia can be sustained, predisposing patients to opportunistic infections. Although remissions achieved with these agents can be long-lasting, minimal residual disease frequently persists. Postremission strategies aimed at eradicating such microscopic diseases can potentially improve the results of purine analog therapy. Alternatively, the up-front combination of these agents with traditional chemotherapy may lead to higher response rates and more sustained remissions.