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 myelodysplasia 6 weeks after commencing chelation with the oral iron chelator deferiprone (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 when 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 desferrioxamine (DFX) (IC50:150 v 9 mu M respectively) to normal myelopoiesis. Delayed addition of iron to myeloid cultures containing an inhibitory concentration of L(1) or DFX was associated with reversal of chelator-induced inhibition of myelopoiesis up to 6 h but not after 24 h. Further studies are needed to determine the incidence and elucidate the pathogenesis of agranulocytosis associated with L(1) therapy.