THE EFFECT OF DEFERIPRONE (L(1)) AND DESFERRIOXAMINE ON MYELOPOIESIS USING A LIQUID CULTURE SYSTEM

Agranulocytosis was observed in a 63-year-old patient with myelodyspla sia 6 weeks after commencing chelation with the oral iron chelator def eriprone (1,2-dimethyl-3-hydroxypyrid-4-one, L(1)) at a daily dose of 79 mg/kg. Using a liquid culture system no difference was observed whe n L(1) toxicity to normal and patient myelopoiesis was compared (IC50: 150 v 172 mu M respectively). L(1) was found to be less toxic than des ferrioxamine (DFX) (IC50:150 v 9 mu M respectively) to normal myelopoi esis. Delayed addition of iron to myeloid cultures containing an inhib itory concentration of L(1) or DFX was associated with reversal of che lator-induced inhibition of myelopoiesis up to 6 h but not after 24 h. Further studies are needed to determine the incidence and elucidate t he pathogenesis of agranulocytosis associated with L(1) therapy.