18 POTENT ACTIVITY OF 2-CHLORODEOXYADENOSINE IN CHRONIC LYMPHOCYTIC LEUKEMIA, HAIRY CELL LEUKEMIA, AND AUTOIMMUNE HEMOLYTIC ANEMIA

Unlike other nucleoside anti-metabolites, 2-chlorodeoxyadenosine is selectively toxic at nanomolar concentrations to human lymphocytes and monocytes. In susceptible cells, the drug causes a dose- and time-dependent accumulation of DNA strand breaks, with resultant activation of poly(ADP-ribose) polymerase. Furthermore, the actions of 2-chlorodeoxyadenosine are entirely independent of replicative DNA synthesis. For this reason, we reasoned that 2-chlorodeoxyadenosine would represent a useful agent for the treatment of slowly replicating lymphoid malignancies, and for the therapy of chronic autoimmune diseases. In the present study, 2-chlorodeoxyadenosine was administered to 18 patients wich advanced chronic lymphocytic leukemia, 4 of whom had concurrent autoimmune hemolytic anemia. An overall response rate of 56% was achieved. Only minor and reversible bone marrow suppression occurred during treatment, indicating a high degree of lymphocyte selectivity. Moreover, 3 of the 4 patients with autoimmune hemolytic anemia had complete resolution of hemolysis. Three patients with hairy cell leukemia also received 2-chlorodeoxyadenosine therapy. Two of the patients achieved clinical remission after one course of the drug. These results demonstrate that 2-chlorodeoxyadenosine is a safe and potent anti-lymphocyte and immunosuppressive agent. Further trials of the drug in autoimmune and lymphoproliferative diseases are warranted.