deferitrin and Transfusion-Reaction

Deferiprone (L1), and appropriate combinations with deferoxamine (DFO), can be used effectively for the treatment of thalassemia and other transfusional iron loading conditions. A number of experimental iron chelators such as deferasirox or ICL670 or Exjade (4-(3,5-bis (2-hydroxyphenyl)-1,2,4-triazol-1-yl)-benzoic acid), deferitrin (4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methylthiazole-4 (S)-carboxylic acid) or GT56-252, 1-allyl-2-methyl-3-hydroxypyrid-4-one or L1NAll and starch DFO polymers, are under clinical evaluation. ICL670 is the most advanced in development and appears to be effective in reducing liver iron in some patients but is overall ineffective in causing negative iron balance. It is also suspected that it is not effective in cardiac iron removal. Combination therapies using L1, DFO and new iron chelating drugs may cause higher efficacy and lower toxicity by comparison to monotherapies. However, several limitations including the high cost of the new chelating drugs may not facilitate the availability of these new treatments to the vast majority of thalassemia patients, most of whom live in developing countries.

Topics: Benzoates; Carboxylic Acids; Chelation Therapy; Clinical Trials as Topic; Deferasirox; Deferiprone; Deferoxamine; Drug Evaluation; Drug Therapy, Combination; Forecasting; Hemochromatosis; Humans; Hydroxyethyl Starch Derivatives; Iron Chelating Agents; Iron Overload; Molecular Structure; Pyridones; Starch; Thalassemia; Thiazoles; Transfusion Reaction; Triazoles

Iron chelation therapy using deferoxamine or deferiprone (L1) is effective for the treatment of most transfused iron-loaded patients. The combination administration of deferiprone in the daytime and deferoxamine in the night appears to be universally effective in rapidly achieving negative iron balance. The cardiac iron removal effect of deferiprone increases the prospects of longer survival in beta-thalassaemia patients. New chelators have reached the stage of clinical development such as deferitrin, 1-allyl-2-methyl-3-hydroxypyrid-4-one (L1NAll) and the starch deferoxamine polymers. Deferasirox has received a conditional approval in the US under the FDA-accelerated approval regulations, but needs further verification of its efficacy and safety. Future iron chelation therapies are likely to be based on combinations of chelating drugs.

Topics: beta-Thalassemia; Carboxylic Acids; Clinical Trials as Topic; Deferiprone; Deferoxamine; Drug Design; Drug Therapy, Combination; Humans; Iron Chelating Agents; Iron Overload; Pyridones; Thiazoles; Transfusion Reaction