Non-Hodgkin's lymphoma: the evolving role of purine analogues

Indolent non-Hodgkin's lymphoma is the commonest form of lymphoma in the USA and Europe, with a long natural history with multiple responses and relapses. Indolent lymphomas include follicular lymphomas (the more frequent subtype), immunocytoma, and small lymphocytic lymphomas according to the Revised European-American Lymphoma classification. The tendency has been to use simple oral medication until patients have more advanced aggressive disease but new agents such as the purine analogues have led to re-evaluation of this approach. The newer purine analogues -- fludarabine, 2-chlorodeoxyadenosine (cladribine) and deoxycoformycin (pentostatin) -- are a group of potently lymphotoxic antimetabolite molecules. Their activity in the indolent non-Hodgkin's lymphomas, in particular in the follicular subtype, may be due to their unique ability as antimetabolites to inhibit resting as well as dividing cells. Within the last decade they have moved from salvage therapy to front-line studies. Further insight into the mechanism of action of the purine analogues will to lead to further advances in this group of diseases.