Inhibition of adenosine deaminase activity results in cytotoxicity to T lymphoblasts in vivo

We have treated a patient with refractory T-cell acute lymphoblastic leukemia with 2′-deoxycoformycin, a potent inhibitor of the enzyme adenosine deaminase. Inhibition of adenosine deaminase activity resulted in (1) an abrupt rise in plasma deoxyadenosine, but not adenosine, concentrations; (2) accumulation of deoxyadenosine triphosphate by lymphoblasts; (3) inhibition of the enzyme S- adenoylhomocysteine hydrolase; and (4) rapid lysis of the leukemic cells. The patient died suddenly 3 days after therapy was discontinued, and postmortem examination revealed a complete absence of leukemic cells in all organs. Pharmacologic inhibition of adenosine deaminase activity can result in the lysis of T lymphoblasts in vivo, and this effect appears to be mediated by deoxyadenosine.