New purine analogues for the treatment of chronic B-cell malignancies.

Adenosine deaminase (ADA), a purine salvage pathway enzyme, appears to play a key role in normal lymphocyte growth, development, and differentiation. Three new purine nucleoside analogues, deoxycoformycin, fludarabine, and 2-chlorodeoxyadenosine, affect the normal function of the purine salvage pathway by inhibiting ADA or by acting as analogs of the ADA substrates. These agents show significant activity in the treatment of chronic B-cell leukemias and low-grade lymphomas. The pharmacology, mechanism of action, and clinical usefulness of these agents are discussed.