The effect of deferiprone (L1) 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, L1) at a daily dose of 79 mg/kg. Using a liquid culture system no difference was observed when L1 toxicity to normal and patient myelopoiesis was compared (IC50: 150 v 172 microM respectively). L1 was found to be less toxic than desferrioxamine (DFX) (IC50: 150 v 9 microM respectively) to normal myelopoiesis. Delayed addition of iron to myeloid cultures containing an inhibitory concentration of L1 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 L1 therapy.
al-Rafaie
F N
FN
Department of Haematology, Royal Free Hospital School of Medicine, London.
Wilkes
S
S
Wonke
B
B
Hoffbrand
A V
AV
D000380:Agranulocytosis / Q000139:chemically induced* / Q000473:pathology; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D011728:Pyridones / Q000009:adverse effects / Q000494:pharmacology*
D011728:Pyridones; D000077543:Deferiprone; D003676:Deferoxamine