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Present status and future prospects of oral iron chelation therapy in thalassaemia and other diseases

  • Symposium: Hematology/Oncology—II
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Abstract

In the last few years we have witnessed the emergence of oral chelation which is a new form of therapy for transfusional iron-loaded patients in thalassaemia and other refractory anaemias. The need for a cheap, non-toxic, orally effective iron chelator is paramount because it could potentially save the lives of many thousands of patients. At present, less than 10% of the patients requiring iron chelation therapy worldwide receive the widely used chelating drug desferrioxamine (DF) because of its high cost, oral inactivity and toxicity. The most promising oral iron chelator is 1, 2-dimethyl-3-hydroxypyrid-4-one (L1 or INN: Deferiprone), which has so far been taken by over 450 patients in 15 countries, and in some cases daily for over 4 years with very promising results. L1 was shown at 50–100 mg/kg/day to be effective in bringing patients to negative iron balance. It increases urinary iron excretion, decreases serum ferritin levels and reduces liver iron in multi-transfused iron-loaded patients. Toxic side effects were mainly encountered at high doses (80–100 mg/kg/day) and include transient agranulocytosis (5 cases), transient musculoskeletal and joint pains (10–20%), gastric intolerance (2–6%) and zinc deficiency (1%). The incidence of these toxic side effects was reduced by using lower doses of 50–75 mg/kg/day. The overall efficacy and toxicity of L1 is comparable to that of DF in animals and humans. Further work is required for identifying susceptible individuals to L1 toxicity, and also optimum dose protocols of L1 which can maximise iron excretion and minimise the incidence of toxic side effects.

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References

  1. World Health Organisation. Community control of hereditary anaemias.WHO Bull 1983; 61: 63–80.

    Google Scholar 

  2. Modell B, Berdoukas V.The Clinical Approach to Thalassaemia. London: Grune and Stratton, 1984.

    Google Scholar 

  3. Buckner CD, Gale RP, Lucarelli G, eds.Advances and Controversies in Thalassaemia Therapy, Bone Marrow Transplantation and Other Approaches. New York: Alan R. Liss Pub. 1989.

    Google Scholar 

  4. Weatherall DJ, Glegg JB.The Thalassaemia Syndromes. 3rd edn. oxford: Blackwell Scientific Publications, 1981.

    Google Scholar 

  5. Kontoghiorghes GJ. Advances in oral iron chelation in man.Intern J Haematol 1992; 55: 27–38.

    CAS  Google Scholar 

  6. Halliwell B, Gutteridge JMC. Oxygen, free radicals and iron in relation to biology and medicine: Some problems and concepts.Arch Bioch Biophys 1986; 246: 501–514.

    Article  CAS  Google Scholar 

  7. Agarwal MB.Living with Thalassaemia. Bombay: Bhalani Book Depot 1986.

    Google Scholar 

  8. Angastiniotis M. Cost of desferrioxamine treatment. In: Abstracts,1st International Conference on Oral Chelators (ICOC). London, UK: 1989: 34.

  9. Brown EB. Thalassaemia.Prog Clin Biol Res 1983; 121: 33–42.

    Google Scholar 

  10. Anderson WF, Hiller MC, eds. Development of iron chelators for clinical use. National Institute of Health. Bethesda, U.S.A. 1975: 1–277.

    Google Scholar 

  11. Martell A.E., Anderson WF, Badman DG, eds.Development of Iron Chelators for Clinical Use. Amsterdam: Elsevier Scientific Publishers, 1980; 1–311.

    Google Scholar 

  12. Avramovici-Grisaru S, Sarel S, Link G, Hershko C. Synthesis of iron Bis (pyridoxal isonicotinoyl hydrazones) and thein vivo iron removal properties of some pyridoxal derivatives.J Med Chem 1983; 26: 298–302.

    Article  PubMed  CAS  Google Scholar 

  13. Neilands JB. Iron absorption and transport in micro-organisms.Ann Rev Nutr 1981; 1: 27–46.

    Article  CAS  Google Scholar 

  14. Kontoghiorghes GJ:The Design of Orally Active Iron Chelators for the Treatment of Thalassaemia. PhD thesis, University of Essex, Colchester, UK. British Library Microfilm No. D66194/86, 1982.

    Google Scholar 

  15. Callender ST, Weatherall DJ. Iron chelation with oral desferrioxamine.Lancet 1980: ii: 689.

    Article  Google Scholar 

  16. Kontoghiorghes GJ, Marcus RE, Huehns ER. Desferrioxamine suppositories.Lancet 1983; ii: 454.

    Article  Google Scholar 

  17. Speyer JL, Green MD, Zeleniuch-Jaquotte A et al. ICRF-187 permits longer treatment with doxorubicin in women with breast cancer.J Clin Oncol 1992; 10: 117–127.

    PubMed  CAS  Google Scholar 

  18. Greenwalt TJ, Ayers VI. Calcium disodium EDTA in transfusion haemosiderosis.Am J Clin Pathol 1955: 25: 266–271.

    PubMed  CAS  Google Scholar 

  19. Pippard MJ, Jackson MJ, Hoffman K et al. Iron chelation using subcutaneous infusion of diethylene triamine penta-acetic acid (DTPA).Scand J Haematol 1986; 36: 466–472.

    Article  PubMed  CAS  Google Scholar 

  20. Peterson CM, Graziano JH, Grady RW et al. Chelation studies with 2, 3-dihydroxybenzoic acid in patients with thalassaemia major.Br J Haematol 1976; 209: 342–348.

    Google Scholar 

  21. Grady RW, Peterson CM, Jones RL et al. Rhodotorulic acid-investigation of its potenial as an iron chelating drug.J Pharmacol Exp Ther 1979; 209: 342–348.

    PubMed  CAS  Google Scholar 

  22. Cerami A, Grady RW, Peterson CM et al. The status of new iron chelators.Ann NY Acid Sci 1980; 344: 415–435.

    Google Scholar 

  23. Brittenham GM. Pyridoxal isonicotinoyl hydrazone, an effective chelator after oral administration.Semi Haematol 1990; 27: 112–116.

    CAS  Google Scholar 

  24. Byers BR, Arceneaux JEL, Gaimes CG et al. Isolation of microbial iron chelators. Some possible effects of their chemotherapeutic use. In: Anderson WF, Hiller MC, eds.Development of Iron Chelators For Clinical Use. National Institute of Health, Bethesda, USA. 1975: 213–228.

    Google Scholar 

  25. Koning J, Palmer P, Franks GR et al. Cardioxane-ICRF 187. Towards anticancer drug specificity through selective toxicity reduction.Cancer Treat Rev 1991: 18: 1–19.

    Article  PubMed  CAS  Google Scholar 

  26. Khalifa AS, Sallam TH, Ghaleb H et al. Salicyl-hydroxamic acid (SHAM); a new oral iron chelator for transfusion induced hemosiderosis in beta thalassaemia major.Blood 1990; 76: 65a.

    Google Scholar 

  27. Grady WR, Hershko C. An evaluation of the potential of HBED as an orally effective iron chelating drug.Semin Haematol 1990; 27 95–100.

    Google Scholar 

  28. Grady RW, Giardina PJ, Salbe AD et al. HBED: Evaluation as an orally effective iron chelator. Abstracts,4th International Conference on Oral Chelators, ICOC, Limassol, Cyprus. 1993: 22.

  29. Kontoghiorghes GJ. Design, properties and effective use of the oral chelator L1 and other α-ketohydroxypyridines in the treatment of transfusional iron overload in thalassaemia.Ann NY Acad Sci 1990; 612: 339–350.

    Article  PubMed  CAS  Google Scholar 

  30. Kontoghiorghes GJ. Orally active α-ketohydroxypyridine iron chelators: studies in mice.Mol Pharmacol 1986; 30: 670–673.

    PubMed  CAS  Google Scholar 

  31. Kontoghiorghes GJ, Sheppard L, Barr J. Synthetic methods andin vitro iron binding studies of the novel 1-alkyl-2-ethyl-3-hydroxypyrid-4-ones.Inorg Chim Acta; 1988; 152:192–199.

    Article  Google Scholar 

  32. Kontoghiorghes GJ, Sheppard LN. Process for producing pyrid-4-ones.European Patent Application 1989; No. 0335745.

  33. Kontoghiorghes GJ, Barr J, Nortey P et al. Selection of a new generation of orally active α-ketohydroxypyridine iron chelators intended for use in the treatment of iron overload.Am J Haematol 1993; 42: 440–444.

    Article  Google Scholar 

  34. Kontoghiorghes GJ, Sheppard LN, Hoffbrand AV et al. 1-Ethyl-2-methyl-3-hydroxypyrid-4-one(L1NEt). A new orally effective iron chelator for the treatment of transfusional iron overload.Blood 1990; 76: 66a.

    Google Scholar 

  35. Porter JB, Weir TB, Marshall L et al. Clinical trials with the orally active hydroxypyridone CP94: Implications for future strategies in iron chelation therapy. Abstracts, 4thInternational Conference on Oral Chelators, ICOC. Limassol, Cyprus 1993: 18.

  36. Porter JB, Gyparaki M, Burker LC et al. Iron mobilisation from hepatocyte monolayer cultures by chelators: The importance of membrane permeability and iron-binding constants.Blood 1988; 72: 1497–1503.

    PubMed  CAS  Google Scholar 

  37. Porter JB, Morgan JM, Hoyes KP et al. Relative efficacy and toxicity of hydroxypyridin-4-one iron chelators.Blood 1990; 76: 2389–2396.

    PubMed  CAS  Google Scholar 

  38. Bergeron RJ, Streiff RR, Wiegand J et al. A comparison of the iron-clearing properties of 1, 2-dimethyl-3-hydroxy-pyrid-4-one, 1, 2-diethyl-3-hydroxy-pyrid-4-one and deferioxamine.Blood 1992; 79: 1882–1890.

    PubMed  CAS  Google Scholar 

  39. Grady R, Srinivasan R, Lemeft R et al. DMHP (L1) and DEHP (CP94): Evidence of toxicity in rats. Abstracts, 3rdInternational Conference on Oral Chelators, ICOC. Nice, France 1991: 11.

  40. Sheppard LN, Kontoghiorghes GJ, Competition between deferiprone, desferrioxamine and other chelators for iron and the effect of other metals.Drug Res 1993; 43: 659–663.

    CAS  Google Scholar 

  41. Kontoghiorghes GJ, Sheppard LN, Chambers S. New synthetic approach and iron chelating studies of 1-alkyl-2-methyl-3-hydroxypyrid-4-ones.Drug Res 1987; 37: 1099–1102.

    CAS  Google Scholar 

  42. Motekaitis RJ, Martell AE. Stabilities of the iron (III) chelates of 1, 2-dimethyl-3-hydroxy-4-pyridinone and related ligands.Inorg Chim Acta 1991; 183: 71–80.

    Article  CAS  Google Scholar 

  43. Kontoghiorghes GJ, Chambers S, Hoffbrand AV. Comparative study of iron mobilisation from haemosiderin, ferritin and iron (III) precipitates by chelators.Biochem J 1987; 241: 87–92.

    PubMed  CAS  Google Scholar 

  44. Kontoghiorghes GJ. The study of iron mobilisation from transferrin using α-ketohydroxy heteroaromatic chelators.Biochim Biophys Acta 1986; 869: 141–146.

    PubMed  CAS  Google Scholar 

  45. Kontoghiorghes GJ. Iron mobilisation from lactoferrin by chelators at physiological pH.Biochem Biophys Acta 1986; 882: 267–270.

    PubMed  CAS  Google Scholar 

  46. Kontoghiorghes GJ. Decreased solubilisation of ferritin iron and fresh iron (III) precipitate following repeated chelator treatments.Inorg Chim Acta 1987; 138: 36–40.

    Article  Google Scholar 

  47. Kontoghiorghes GJ. Orally active α-ketohydroxypyridine iron chelators. Effects on iron and other metal mobilisations.Acta Haematol 1987; 78: 212–216.

    PubMed  CAS  Google Scholar 

  48. Ganeshaguru K, Lally KM, Piga A et al. Cytotoxic mechanisms of iron chelators.Drugs Today 1992; 28 (suppl. A): 29–34.

    CAS  Google Scholar 

  49. Kontoghiorghes GJ, Jackson MI, Lunec J.In vitro screening of iron chelators using models of free radical damage.Free Radic Res Commun 1986; 2: 115–124.

    PubMed  CAS  Google Scholar 

  50. Kontoghiorghes GJ, Piga A, Hoffbrand AV. Cytotoxic effects of the lipophilic iron chelator omadine.FEBS LETT 1986; 204: 208–212.

    Article  PubMed  CAS  Google Scholar 

  51. Cunningham JM, Hunter A, Francis GE et al. Differrential cytotoxicity of oral iron chelators and desferrioxamine to human bone marrow haemopoietic progenitor cellsin vitro.Br J Haematol 1991; 77 (suppl. 1): 381.

    Google Scholar 

  52. Sharnetzky M, Konig R Lamomek M et al. Prophylaxis of systemic yersiniasis in Thalassaemia major.Lancet 1984: ii: 791.

    Article  Google Scholar 

  53. Boelaert JR, de Locht M, Schneider YJ. Mucormycosis and desferrioxamine (DFO), Susceptibility of different zygomycetes to DFO. Abstracts, 4thInternational Conference on Iron Chelators, ICOC. Limassol, Cyprus 1993: 13.

  54. Van Cutsem J, Boelaert JR. Effects of deferoxamine, feroxamine and iron on experimental mucormycosis (zygomycosis).Kidney Inter 1989; 36: 1061–1068.

    Article  Google Scholar 

  55. Brock JH, Liceaga J, Kontoghiotghes GJ. The effect of synthetic iron chelators on bacterial growth in human serum.FEMS Microbiol Immunol 1988; 47: 55–60.

    Article  CAS  Google Scholar 

  56. Weinberg ED. Iron and infection.Microbiol Rev 1978; 42: 45–66.

    PubMed  CAS  Google Scholar 

  57. Kontoghiorghes GJ, Aldouri MA, Hoffbrand AV et al. Effective chelation of iron in β-thalassaemia with the oral chelator 1, 2-dimethyl-3-hydroxypyrid-4-one.Br Med J 1987; 2295: 1509–1512.

    Google Scholar 

  58. Kontoghiorghes GJ, Aldouri MA, Sheppard LN et al. 1, 2-Dimethyl-3-hydroxypyrid-4-one, on orally active chelator for the treatment of transfusional iron overload.Lancet 1987; i: 1294–1295.

    Article  Google Scholar 

  59. Tondury P, Kontoghiorghes GJ, Ridolfi-Luthy R et al. L1 (1, 2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with β-thalassaemia major.Br J Haematol 1990; 76: 550–553.

    PubMed  CAS  Google Scholar 

  60. Olivieri NF, Koren G, Hermann C et al. Comparison of oral iron chelator L1 and desferrioxamine in iron loaded patients.Lancet 1990; ii: 1275–1279.

    Article  Google Scholar 

  61. Agarwal MB, Viswanathan C, Ramanathan J et al. Oral iron chelation with L1.Lancet 1990; i: 601.

    Article  Google Scholar 

  62. Kontoghiorghes GJ, Bartlett AN, Hoffbrand AV et al. Long term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). (1) Iron chelation and metabolic studies.Br J Haematol 1990; 76: 295–300.

    PubMed  CAS  Google Scholar 

  63. Goudsmit R, Kersten MJ. Long term treatment of transfusion hemosiderosis with the oral iron chelator L1.Drugs Today 1992; 28 (suppl. A): 133–135.

    Google Scholar 

  64. Korkina LG, Afanas'ev IB, Deeva IB et al. Free radical status of blood of patients with iron overload: the effect of chelating treatment.Drugs Today 1992; 28 (suppl A): 137–141.

    Google Scholar 

  65. Jaeger M, Aul C, Sohngen D et al. Iron overload in polytransfused patients with MDS; Use of L1 for oral iron chelation.Drugs Today 1992; 28 (suppl A): 143–147.

    Google Scholar 

  66. Carnelli V, Spadaro C, Stefano V et al. L1 efficacy and toxicity in poorly compliant and for refractory to desferrioxamine thalassaemia patients: Interim report.Drugs Today 1992; 28 (suppl. A): 119–121.

    Google Scholar 

  67. Kontoghiorghes GJ, Barr J, Baillot R. Studies of aluminium mobilisation in renal dialysis patients using the oral chelator 1, 2-dimethyl-3-hydroxypyrid-4-one.Drug Res (In Press).

  68. Vreugdenhil G, Kontoghiorghes GJ, Van Eijk HG et al. Impaired erythropoietin responsiveness to the anemia in rheumatoid arthritis. A possible inverse relationship with iron stores and effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one.Clin Exp Rheumatol 1991; 9: 35–40.

    PubMed  CAS  Google Scholar 

  69. Oral chelation in the treatment of thalassaemia and other diseases.Drugs Today 1992; 28 (suppl A): 1–187.

    Google Scholar 

  70. Olivieri NF, Koren G, Matsuii D et al. Reduction of tissue iron stores and normalisation of serum ferritin during treatment with the oral iron chelator L1 in thalassaemia intermedia.Drugs Today 1992; 28 (Suppl. A): 123–132.

    Google Scholar 

  71. Tondury P. L1 for oral chelation in patients with thalassaemia: results of clinical trials in Switzerland. Abstracts, 4thInternational Conference on Iron Chelators, ICOC. Limassol, Cyprus 1993: 24.

  72. Kontoghiorghes GJ, Goddard JG, Bartlett AN et al. Pharmacokinetic studies in humans with the oral iron chelator 1, 2-dimethyl-3-hydroxypyrid-4-one.Clin Pharm Ther 1990; 48: 255–261.

    Article  CAS  Google Scholar 

  73. Rahman YE, Railkar AM, Venkataram S. Pharmacodynamics and pharmacokinetics of 1, 2-dimethyl-3-hydroxypyrid-4-one (DMHP) or L1 in rat, rabbit and dog models.Drugs Today 1992; 28 (suppl. A): 55–63.

    CAS  Google Scholar 

  74. Kontoghiorghes GJ. Metabolism and site of action of L1 (deferiprone). No evidence that L1 biotransformation effects iron excretion. Abstracts, 4thInternational Conference on Iron Chelators, ICOC. Limassol Cyprus 1993: 20.

  75. Sheppard L, Kontoghiorghes GJ. Synthesis and metabolism of L1 and other novel alpha-ketohydroxypyridine iron chelators and their metal complexes.Drugs Today 1992; 28 (Suppl A): 3–10.

    CAS  Google Scholar 

  76. Olivieri NF, Templeton DM, Koren G et al. Evaluation of the oral iron chelator 1, 2-3-dimethyl-3-hydroxypyrid-4-one (L1) in iron loaded patients.Ann NY Acad Sci 1990; 612: 369–377.

    Article  PubMed  CAS  Google Scholar 

  77. Nielsen P, Frtjes M, Drescow B et al. The iron-decorporating effect of L1 in normal and TMH-ferrocene iron loaded rats and in one patient with post-transfusional siderosis as judged by59Fe-labelling technique.Drugs Today 1992; 28 (suppl. A): 45–53.

    CAS  Google Scholar 

  78. Kontoghiorghes GJ. Chelators affecting iron absorption in mice.Drug Res 1990; 40: 1332–1335.

    CAS  Google Scholar 

  79. Kontoghiorghes GJ, Bartlett AN, Hoffbrand AV et al. Intensive chelation and metabolic studies using oral 1, 2-dimethyl-3-hydroxypryrid-4-one (L1).Br J Haematol 1990; 74 Suppl. 1: 10.

    Google Scholar 

  80. Evans RW, Sharma M, Ogwang W et al. The effect of alpha-ketohydroxypyridine chelators on transferrin saturationin vitro andin vivo.Drugs Today 1992; 28 (Suppl A): 19–23.

    CAS  Google Scholar 

  81. Agarwal MB, Gupta SS, Viswanathan C et al. Long term assessment of efficacy and safety of L1, an oral iron chelator in transfusion dependent thalassaemia: Indian trial.Br J Haematol 1992;82:460–466.

    PubMed  CAS  Google Scholar 

  82. Agarwal MB, Gupta SS, Viswanathan C et al. Long term assessment of efficacy and toxicity of L1 (1, 2-dimethyl-3-hydroxypyrid-4-one) in transfusion dependent thalassaemia. Indian trial.Drugs Today 1992;28(Suppl A):107–114.

    Google Scholar 

  83. Tondury P, Wagner HP, Kontoghiorghes GJ. Update of long-term clinical trials with L1 in beta-thalassaemia patients in Berne, Switzerland.Drugs Today 1992;28 (Suppl A):115–117.

    Google Scholar 

  84. De Virgilis S, Cognia M, Turco MP et al. Depletion of trace elements and acute occular toxicity induced by desferrioxamine in patients with thalassaemia.Arch Dis Child 1988;63:250–255.

    Google Scholar 

  85. Zaino EC. Deferrioxamine and trance metal excretion In: Zaino EC, and Roberts RH, eds.Chelation Therapy in Chronic Iron Overload. Symposia Specialist Pub. Miami: U.S.A. 1977:95–101.

  86. Alrefai FN, Wonke B, Hoffbrand AV et al. Efficacy and possible adverse effects of the oral iron chelator 1, 2-dimethyl-3-hydroxypyrid-4-one (L1) in thalassaemia major.Blood 1992;80:593–599.

    Google Scholar 

  87. Kontoghiorghes GJ. Oral iron chelation is here.Br Med J 1991;303:1279–1280.

    CAS  Google Scholar 

  88. Kontoghiorghes GJ. Dose response studies using desferrioxamine and orally active chelators in a mouse model.Scand J Haematol 1986;37:63–70.

    Article  PubMed  CAS  Google Scholar 

  89. Kontoghiorghes GJ, Sheppard LN, Hoffbrand AV et al. Iron chelation studies using desferrioxamine and the potential oral chelator 1, 2-dimethyl-3-hydroxypyrid-4-one in normal and iron loaded rats.J Clin Path 1987;40:404–408.

    Article  PubMed  CAS  Google Scholar 

  90. Kontoghiorghes GJ, Nasseri-Sina P, Goddard JG et al. Safety of iron chelator L1.Lancet 1989;ii:457–458.

    Article  Google Scholar 

  91. Porter JB, Hayes KP, Abeysinghe R et al. Animal toxicity of iron chelator L1.Lancet 1989;ii:156.

    Article  Google Scholar 

  92. Nortey P, Barr J, Matsakis M et al. Effect on iron excretion and animal toxicology of L1 and other alpha-ketohydroxypyridine chelators.Drugs Today 1992;28 (Suppl A):81–88.

    CAS  Google Scholar 

  93. Grady RW, Srinivasan R, Dunn JB et al. Evidence of toxicity due to 1, 2-dimethyl-3-hyydroxypyrid-4-one (L1) in normal rats.Drugs Today 1992;28 (Suppl A):73–79.

    CAS  Google Scholar 

  94. Biesemeier JA, Laveglia J. 14-day oral toxicity study in dogs with 1, 2-dimethyl-3-hydroxypyrid-4-one (DMHP L1).Food and Drug Research Laboratories, Waverley, New York: 1991:1–102 and appendices (I-1)-(V-3).

    Google Scholar 

  95. Berdoukas V, Bentley P, Frost H et al. Toxicity of oral iron chelator L1.Lancet. 1993;341:1088.

    Article  PubMed  CAS  Google Scholar 

  96. Kontoghiorghes GJ, Agarwal MB, Tondury P et al. Future of oral iron chelator deferriprone (L1).Lancet 1993;1:1479–1480.

    Article  Google Scholar 

  97. Hershko C. Development of oral iron chelator L1.Lancet 1993;343:1088–1089.

    Article  Google Scholar 

  98. Ciba Report on Desferal. Adverse Drug Reaction Centre. Information No. 2. October 1965. pp 1–38.

  99. Kontoghiorghes GJ, Hoffbrand AV. Orally active alpha-ketohydroxypyridine iron chelators intended for clinical use:In vivo studies in rabbits.Br J Haematol 1986;62:607–613.

    PubMed  CAS  Google Scholar 

  100. Kontoghiorghes GJ, Bartlett AH, Hoffbrand AV. Prospects for effective oral iron chelation therapy in man with 1,2-dimethyl-3-hydroxypyrid-4-one and other alpha-ketohydroxypyridines.Prog Clin Biol Res 1989;309:107–114.

    PubMed  CAS  Google Scholar 

  101. Agarwal MB, Gupta SS, Viswanathan G et al. Long term efficacy and toxicity of L1 and iron chelator in transfusion dependent thalassaemics over the last three and a half years. Abstracts,4th International Conference on Oral Chelators, ICOC, Limassol, Cyprus 1993:23.

  102. Hoffbrand AV, Bartlett AN, Veys P et al. Agranulocytosis and thrombocytopenia in a patient with Blackfan Diamond anaemia during oral chelator trial.Lancet 1989;ii:457.

    Article  Google Scholar 

  103. Kersten MJ, Lange R, Goudsmit R et al. Long term treatment of transfusional iron overload with the oral iron chelator 1, 2-dimethyl-3-hydroxypyrid-4-one. Abstracts,4th International Congress on Oral Chelators, ICOC, Limassol, Cyprus. 1993:27.

  104. Young GAR, Vincent PC. Drug induced agranulocytosis.Clin Haematol 1980;9:483–504.

    PubMed  Google Scholar 

  105. Uetrecht JP. Idiosyncratic drug reaction. Possible role of reactive metabolites generated by leukocytes.Pharmacol Res 1989; 6:265–273.

    Article  CAS  Google Scholar 

  106. Uetrecht JP. Drug metabolism by leukocytes and its role in drug-induced lupus and other idiosyncratic drug reactions.Toxicology 1900;20:213–235.

    Google Scholar 

  107. Hoffbrand AV, Kontoghiorghes GJ. Protocol for monitoring efficacy and toxicity in clinical trials with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1).Drugs Today 1992;28 (Suppl A):149–155.

    Google Scholar 

  108. Freedman MH, Grisary D, Olivieri NF et al. Pulmonary syndrome in patients with thalassaemia major receiving intravenous desferioxamine infusions.Am J Dis Child 1990;144:565–569.

    PubMed  CAS  Google Scholar 

  109. Zervas J, Kyriakou D, Konstantopoulos K et al. Acute myelopathy after high dose desferrioxamine administration intravenously. In: Abstracts3rd International Conference on Thalassaemia and the Haemoglobinopathies. Gagliari. Italy. 1989:162.

  110. Olivieri NF, Buncic RJ, Chew E et al. Visual and auditory neurotoxicity in patients receiving subcutaneous desferrioxamine infusions.N Engl J Med 1986; 314:869–873.

    Article  PubMed  CAS  Google Scholar 

  111. Polson RJ, Jame A, Bomford A et al. Treatment of rheumatoid arthritis with desferrioxamine: relation between stores of iron before treatment and side effects.Br Med J 1985;291:448.

    CAS  Google Scholar 

  112. De Virgillis S, Cognia M, Fracia F et al. Desferrioxamine induced growth retardation in patients with thalassaemia major.J Paediatr 1988;113:661–669.

    Article  Google Scholar 

  113. Politis C, Vrettou H, Fragatou S et al. Reactions to subcutaneous application of iron chelation therapy with desferri-oxamine. An urgent need for oral chelators. Abstracts,4th International Congress on Oral Chelators, ICOC. Limassol, Cyprus. 1993:4.

  114. Nebeker HG, Milliner DS, Ott SA et al. Aluminium-related osteomalagia. Clinical response to desferrioxamine.Kidney Int 1984;25:173.

    Google Scholar 

  115. Walker JA, Sherman RA, Eisenfer RP. Thrombocytopenia associated with intravenous desferrioxamine.Am J Kidney Dis 1985;6:254–256.

    PubMed  CAS  Google Scholar 

  116. Zurlo MG, De Stefano P, Borgna-Pignatti C et al. Survival and causes of death in thalassaemia major.Lancet 1989;ii:27–29.

    Article  Google Scholar 

  117. Kurtzman NA, ed. Toxicity from aluminium and iron: Recognition, treatment and prevention.Sem Nephrol 1986; Suppl 1:1–41.

    Google Scholar 

  118. Kontoghiorghes GJ, Barr J, Baillot R. Aluminium mobilisation in renal dialysis patients using the oral chelator 1, 2-dimethyl-3-hydroxypyrid-4-one (L1).Drugs Today 1992;28 (Suppl. A):183–187.

    Google Scholar 

  119. Giordano N, Sancasciani S, Borghi C et al. Antianemic and potential anti-inflammatory activity of desferrioxamine: Possible usefulness in rheumatoid arthritis.Clin Exp Rheumatol 1986;4:25–29.

    PubMed  CAS  Google Scholar 

  120. Vreugdenhil G, Van Eijk HG, Swaak AJG. Iron and iron chelators in rheumatoid arthritis.Drugs Today 1992;28 (Suppl A):157–163.

    Google Scholar 

  121. Heppner DG, Hallaway PE, Kontoghiorghes GJ et al. Antimalaria properties of orally active iron chelators.Blood 1988; 72:358–361.

    PubMed  CAS  Google Scholar 

  122. Gordeuk VR, Thuma PE, Brittenham GM et al. Iron chelation with desferrioxamine B in adults with asymptomatic P. falciparum parasitemia.Blood 1992;79:308–312.

    PubMed  CAS  Google Scholar 

  123. McLachlan CDR, Dalton AJ, Kruck TPA et al. Intramuscular desferrioxamine in patients with Alzheimer's disease.Lancet; 1991;i:1304–1308.

    Article  Google Scholar 

  124. Estrow ZA, Tawa XH, Dube ID et al.In vitro andin vivo effects of desferioxamine in neonatal acute leukaemia.Blood 1987; 69:757–761.

    Google Scholar 

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  1. Department of Haematology, Royal Free Hospital, School of Medicine, University of London, Pond Street, NW3 2QG, London, U.K.

    George J. Kontoghiorghes

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Kontoghiorghes, G.J. Present status and future prospects of oral iron chelation therapy in thalassaemia and other diseases. Indian J Pediatr 60, 485–507 (1993). https://doi.org/10.1007/BF02751425

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