title: The effect of deferiprone (L1) and desferrioxamine on myelopoiesis using a liquid culture system.
abstract: 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.
authors.affiliation: Department of Haematology, Royal Free Hospital School of Medicine, London.
authors.forename: F N
authors.initials: FN
authors.lastname: al-Rafaie
authors.forename: S
authors.initials: S
authors.lastname: Wilkes
authors.forename: B
authors.initials: B
authors.lastname: Wonke
authors.forename: A V
authors.initials: AV
authors.lastname: Hoffbrand
mesh_terms: 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*
chemical_list: D011728:Pyridones; D000077543:Deferiprone; D003676:Deferoxamine