Iron chelators for thalassaemia

British Journal of Haematology

Volumn 101, Issue 3, 1998, Pages 399-406

  Hershko, Chaim ^a,b   Konijn, Abraham M ^a   Link, Gabriela ^a  

^a HEBREW UNIVERSITY   (Israel)

^b SHAARE ZEDEK MEDICAL CENTER   (Israel)

Author keywords

Deferiprone; Desferroxamine; Iron chelators; Iron toxicity; Thalassaemia

Indexed keywords

CHELATING AGENT; DEFERIPRONE; DEFEROXAMINE; IRCO 11; N,N' BIS(2 HYDROXYBENZOYL)ETHYLENEDIAAMINE DIACETIC ACID; UNCLASSIFIED DRUG;

BONE MALFORMATION; DRUG DESIGN; DRUG INDICATION; EYE TOXICITY; HUMAN; IRON CHELATION; IRON OVERLOAD; LIFE EXPECTANCY; LUNG TOXICITY; NEPHROTOXICITY; ORAL DRUG ADMINISTRATION; PATHOPHYSIOLOGY; PERCEPTION DEAFNESS; PRIORITY JOURNAL; REVIEW; SEPSIS; SUBCUTANEOUS DRUG ADMINISTRATION; THALASSEMIA; TREATMENT OUTCOME; YERSINIA PESTIS;

ADMINISTRATION, ORAL; AZA COMPOUNDS; CHELATING AGENTS; DEFEROXAMINE; EDETIC ACID; HUMANS; IRON; IRON CHELATING AGENTS; IRON OVERLOAD; LONG-TERM CARE; PYRIDONES; THALASSEMIA;

EID: 0031859181     PISSN: 00071048     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2141.1998.00726.x     Document Type: Review

References (77)

1. Agarwal, M.B., Gupte, S.S., Viswanathan, C., Ramanathan. J., Desai, N., Puniyani, R.R. & Chhablani, A.T. (1992) Long-term assessment of efficacy and safety of Ll. an oral iron chelator. in transfusion dependent thalassaemia: Indian trial. British Journal of Haematology, 82, 460-466.
2. Alberti, D., Piga, A., Porter, J.B. & Hassan. I. (1997) Desferrioxamine depot (CGH 749B): a new formulation allowing the prospect of a daily s.c. injection. (Abstract). 8th International Conference, Oral Chelation in the Treatment of Thalassaemia and Other Disease, Corfu, p. 39.
3. Aldouri, M.A., Wonke, B., Hoffbrand, A.V., Flynn, D.M., Ward, S.E., Agnew, J.E. & Hilson, A.J. (1990) High incidence of cardiomyopathy in beta-thalassaemia patients receiving regular transfusion and iron chelation: reversal by intensified chelation. Acta Haematologica 83, 113-117.
4. Al-Refaie, F.N., Hershko, C., Hoffbrand, A.V., Kosaryan, M., Olivieri, N.F., Tondury, P. & Wonke, B. (1995a) Results of long-term deferiprone (L1) therapy: a report of the International Study Group on Oral Iron Chelators. British Journal of Haematology, 91, 224-229.
5. Al-Refaie, F.N. & Hoffbrand, A.V. (1994) Oral iron-chelating therapy: the L1 experience. Clinical Haematology, 7, 941-964.
6. Al-Refaie, F.N., Sheppard, L.N., Nortey, P., Wonke, B. & Hoffbrand, A.V. (1995b) Pharmacokinetics of the oral iron chelator deferiprone (L1) in patients with iron overload. British Journal of Haematology, 89, 403-407.
7. Al-Refaie, F.N., Wickens, D.G., Wonke, B., Kontoghiorghes, G.J. & Hoffbrand, A.V. (1992) Serum non-transferrin-bound iron in beta-thalassaemia major patients treated with desferrioxamine and L1. British Journal of Haematology, 82, 431-436.
8. Araujo, A., Kosaryan, M., MacDowell, A., Wickens, D., Pun, S., Wonke, B. & Hoffbrand, A.V. (1996) A novel delivery system for continuous desferrioxamine infusion in transfusional iron overload. British Journal of Haematology, 93, 835-837.
9. Arden, G.B., Wonke, B., Kennedy, C. & Huehns, E.R. (1984) Ocular changes in patients undergoing long-term desferrioxamine treatment. British Journal of Ophthalmology, 68, 873-877.
10. Borgna-Pignatti, C. & Cohen, A. (1997) Evaluation of a new method of administration of the iron chelating agent deferoxamine. Journal of Pediatrics. 130, 86-88.
11. Breuer, W. Epsztejn, S. & Cabantchik, Z.I. (1997) Dynamics of the cytosolic chelatable iron pool of K562 cells. FEBS Letters, 382, 304-308.
12. Brittenham, G.M., Farrell, D.E., Harris, D.E., Feldman, E.S., Danish, E.H., Muir, D.A., Tripp, J.H. & Bellon, E.M. (1982) Magnetic susceptibility measurement of human iron stores. New England Journal of Medicine. 307, 1671-1675.
13. Brittenham, G.M., Griffith, P.M., Nienhuis, A.W., McLaren, C.E., Young, N.S., Tucker, E.E., Allen, C.J., Farrell, D.E. & Harris, J.W., (1994) Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. New England Journal of Medicine, 331, 567-569.
14. Castriota-Scanderberg, A. & Sacco, M. (1997) Agranulocytosis, arthritis and systemic vasculitis in a patient receiving the oral iron chelator L1 (deferiprone). British Journal of Haematology. 96, 254-255.
15. Chapman, R.W.G., Hussain, M.A.M., Gorman, A., Laulicht, M., Politis, D., Flynn, D.M., Sherlock, S. & Hoflbrand, A.V. (1982) Effect of ascorbic acid deficiency on serum ferritin concentration in patients with beta thalassemia. Journal of Clinical Pathology, 35, 481-486.
16. Cohen, A., for the LA-02 Study Group (1997) A multi-center safety trial of the oral iron chelator deferiprone. (Abstract 26). Seventh Cooley's Anemia Symposium: a New York Academy of Sciences Meeting, Cambridge, Massachusetts.
17. Cohen, A.R., Martin, M. & Schwartz, E. (1990) Current treatment of Cooley's anemia: intravenous chelation therapy. Sixth Cooley's Anemia Symposium (ed. by A. Bank). Annals of the New York Academy of Sciences, 612, 286-292.
18. Cook, J.D., Marsaglia, G. & Eschbach, J.W. (1970) Ferrokinetics: a biologic model for plasma iron exchange in man. Journal of Clinical Investigation, 49, 197-205.
19. De-Sanctis, V. Pinamonti, A., Di-Palma, A., Sprocati, M., Atti. G., Gamberini, M.R. & Vullo, C. (1996) Growth and development in thalassaemia major patients with severe bone lesions due to desferrioxamine. European Journal of Pediatrics, 155, 368-372.
20. De Sanctis, V. Pintor, C. & Aliquo, M.C. (1992) Prevalence of endocrine complications in patients with β-thalassemia major: an Italian multicenter study. Advances in Pediatric Endocrinology (ed. by C. Pintor, E. E. Muller, S. Loche and M. I. New), pp. 127-133. Springer, Berlin.
21. Freedman, M.H., Grisaru, D., Olivieri, N., MacLusky, I. & Thorner, P.S. (1990) Pulmonary syndrome in patients with thalassemia major receiving intravenous deferoxamine infusions. American Journal of Disease in Childhood, 144, 565-569.
22. Gabutti, V. & Borgna-Pignatti, C. (1994) Clinical manifestations and therapy of transfusional haemosiderosis. Clinical Haematology, 7, 919-940.
23. Gabutti, V. & Piga, A. (1996) Results of long-term iron-chelating therapy. Acta Haematologica, 95, 26-36.
24. Gallant, T., Freedman, M.H., Vellend, H. & Francombe, W.H. (1986) Yersinia sepsis in patients with iron overload treated with deferoxamine. New England Journal of Medicine, 314, 1643.
25. Giardina, P.J., Grady, R.W. Ehlers, K.H., Burstein, S., Graziano, J.H., Markenson. A.L. & Hilgartner, M.W. (1990) Current therapy of Cooley's anemia: a decade of experience with subcutaneous desferrioxamine. Sixth Cooley's Anemia Symposium (ed. by A. Bank). Annals of New York Academy of Sciences, 612, 275-285.
26. Grady, R.W., Hilgartner, M.W. & Giardina, P.J. (1996) Deferiprone: its efficacy relative to that of desferal. Thirty-Eighth Annual Meeting, American Society of Hematology, Orlando, Florida. Blood. 88, (Suppl. 1), Abstract 1230.
27. Grady, R.W., Salbe, A.D., Hilgartner, M.W. & Giardina, P.J. (1994) Results from a phase I clinical trial of HBED. Advances in Experimental Medicine and Biology, 356, 351-359.
28. Grady, R.W., Srinivasan, R., Dunn, J.B., Coursey, M.P., Lemert, R.F., Calvano, S.E. & Hilgartner, M.W. (1992) Evidence of toxicity due to 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in normal rats. Drugs of Today, 28, (Suppl. A), 73-80.
29. Gutteridge, J.M.C., Rowley, D.A., Griffiths, E. & Halliwell, B. (1985) Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. Clinical Science, 68, 463-467.
30. Hershko, C., Grady, R.W. & Link, G. (1984) Phenolic ethylenediamine derivatives: a study of orally effective iron chelators. Journal of Laboratory and Clinical Medicine, 103, 337-346.
31. Hershko, C., Graham, G., Bates, G.W. & Rachmilewitz, E.A. (1978) Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity. British Journal of Haematology, 40, 255-263.
32. Hershko, C. & Rachmilewitz, E.A. (1979) Mechanism of desferrioxamine-induced iron excretion in thalassaemia. British Journal of Haematology, 42, 125-132.
33. Hershko, C. & Weatherall, J.D. (1988) Iron chelating therapy. CRC Critical Reviews in Cinical Laboratory Sciences, 26, 303-345.
34. Hider, R.C., Choudhury, R., Rai, B.L., Dehkordi, L.S. & Singh, S. (1996) Design of orally active iron chelators. Acta Haematologica, 95, 6-12.
35. Hider, R.C., Singh, S., Porter, J.B. & Huehns, E.R. (1990) The development of hydroxypyridin-4-ones as orally active iron chelators. Sixth Cooley's Anemia Symposium (ed. by A. Bank). Annals of the New York Academy of Sciences, 612, 327-328.
36. Hoffbrand, A.V. & Wonke, B. (1989) Results of long-term subcutaneous desferrioxamine therapy. Bailliere's Clinical Haematology, 2, 345-359.
37. Hoffbrand, A.V., Wonke, B., Al-Refaie, F., Siritanaratkul, N., Davis, B. & Jackson, B.F.A. (1996) Over 3 year follow up of 56 transfusion dependent patients receiving oral iron chelation. Thirty-Eighth Annual Meeting. American Society of Hematology, Orlando, Florida. Blood. 88, (Suppl. 1), Abstract 2592.
38. Hyman, C.B., Agness, C.L., Rodriguez-Funes, R. & Zednikova, M. (1985) Combined subcutaneous and high-dose intravenous deferoxamine therapy of thalassemia. Annals of the New York Academy of Sciences, 445, 293-303.
39. Jensen, P.D., Heickendorff, L., Pedersen, B., Bendix-Hansen, K., Jensen, F.T., Christensen, T., Boesen, A.M. & Ellegaard, J. (1996) The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. British Journal of Haematology, 94, 288-299.
40. Keberle, H. (1992) From antibiotic to chelating agent. Desferrioxamine: History, Clinical Value, Perspectives (ed. by K. Gross, J. Aumiller and J. Gelzer), pp. 26-36. MMV Medizin Verlag, Berlin.
41. Kersten, M.J., Lange, R., Smeets, M.E., Vreugdenhil, G., Roozendaal, K.J., Lameijer, W. & Goudsmit, R. (1996) Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. Annals of Hematology, 73, 247-252.
42. Klausner, R.D., Rouault, T.A. & Harford, J.B. (1993) Regulating the fate of mRNA: the control of cellular iron metabolism. Cell. 72, 19-28.
43. Kontoghiorghes. G.J. (1990) Design, properties, and effective use of the oral chelator L1 and other α-ketohydroxypyridines in the treatment of transfusional iron overload in thalassemia. Sixth Cooley's Anemia Symposium (ed. by A. Banks). Annals of the New York Academy of Sciences, 612, 339-350.
44. Koren, G., Bentur, Y., Strong, D., Harvey, E., Klein, J., Baumal, R., Spielberg, S.P. & Freedman, M.H. (1989) Acute changes in renal function associated with deferoxamine therapy. American Journal of Disease in Childhood, 143, 1077-1080.
45. L'Eplattenier, F., Murase, I. & Martell, A.E. (1967) New multidentate ligands. VI. Chelating tendencies of N,N′-di(2-hydroxybenzoyl) ethylenediamine-N,N′-diacetic acid. Journal of the American Chemical Society, 89, 837-843.
46. Link, G., Athias, P., Grynberg, A., Pinson, A. & Hershko, C. (1989) Effect of iron loading on transmembrane potential, contraction and automaticity of rat ventricular muscle cells in culture. Journal of Laboratory and Clinical Medicine, 113, 103-111.
47. Link, G., Pinson, A. & Hershko, C. (1985) Heart cells in culture: a model of myocardial iron overload and chelation. Journal of Laboratory and Clinical Medicine, 106, 147-153.
48. Link, G., Pinson, A. & Hershko, C. (1993) Iron loading of cultured cardiac myocytes modifies sarcolemmal structure and increases lysosomal fragility. Journal of Laboratory and Clinical Medicine, 121, 127-134.
49. Link, G., Pinson, A. & Hershko, C. (1994) The ability of orally effective iron chelators dimethyl- and diethyl-hydroxypyrid-4-one and of deferoxamine to restore sarcolemmal thiolic enzyme activity in iron-loaded heart cells. Blood. 83, 2692-2697.
50. Link, G., Tirosh, R., Pinson, A. & Hershko, C. (1996) Role of iron in the potentiation of anthracycline toxicity: identification of heart cell mitochondria as the site of iron-anthracycline interaction. Journal of Laboratory and Clinical Medicine, 127, 272-278.
51. Lombardo, T., Ferro, G., Frontini, V. & Percolla, S. (1996) High-dose intravenous desferrioxamine (DFO) delivery in four thalassemic patients allergic to subcutaneous DFO administration. American Journal of Hematology, 51, 90-92.
52. Marcus, R.E., Davies, S.C., Bantock, H.M., Underwood, S.R., Walton, S. & Huehns, E.R. (1984) Desferrioxamine to improve cardiac function in iron-overloaded patients with thalassaemia major. Lancet, i, 392.
53. Mariotti, E., Agostini, A., Angelucci, K., Cesaroni, P., Lucarelli, G. & Sgarbi, E. (1993) Cardiac study by dobutamine stress echocardiography in thalassemic patients. Bone Marrow Transplantation, 12, (Suppl. 1). 14-15.
54. Olivieri, N.F. (1996a) Long-term therapy with deferiprone. Acta Haematologica, 95, 37-48.
55. Olivieri, N.F., for the Iron Chelation Group (1996b) Long-term follow-up of body iron in patients with thalassemia major during therapy with the orally active iron chelator deferiprone (L1). Thirty-Eighth Annual Meeting, American Society of Hematology, Orlando, Florida. Blood. 88, (Suppl, 1). abstract 1229.
56. Olivieri, N.F. & Brittenham, G.M. (1997) Iron chelating therapy and the treatment of thalassemia. Blood. 89, 739-761.
57. Olivieri, N.F., Brittenham, J.M., Matsui, D., Berkovitch, M., Blendis, L.M., Cameron, R.G., McLelland, R.A., Liu, P.P., Templeton, D.M. & Koren, G. (1995) Iron-chelation therapy with oral deferiprone in patients with thalassemia major. New England Journal of Medicine, 332, 918-922.
58. Olivieri, N.F., Buncic, R.J., Chew, E., Gallanti, T., Harrison, R.V., Keenan, N., Logan, N., Mitchell, D., Ricci, G., Skarf, B., Taylor, M. & Freedman, M.H. (1986) Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions. New England Journal of Medicine, 314, 869-873.
59. Olivieri, N.F., Koren, G., Harris, J., Khattak, S., Freedman, M.H., Templeton, D.M., Bailey, J.D. & Reilly, B.J. (1992) Growth failure and bony changes induced by deferoxamine. American Journal of Pediatric Hematology and Oncology, 14, 48-56.
60. Olivieri, N.F., Nathan, D.G., MacMillan, J.H., Wayne, A.S., Liu, P.P., McGee, A., Martin, M., Koren, G. & Cohen, A.R. (1994) Survival in medically treated patients with homozygous β-thalassemia. New England Journal of Medicine, 331, 574-578.
61. Piga, A., Luzzatto, L., Capalbo, P., Gambotto, S., Tricta, F. & Gabutti, V. (1988) High-dose desferrioxamine as a cause of growth failure in thalassaemic patients. European Journal of Haematology, 40, 380-381.
62. Porter, J.B., Huehns, E.R. & Hider, R.C. (1989a) The development of iron chelating drugs. Clinical Haematology, 2, 257-292.
63. Porter, J.B., Jaswon, M.B., Huehns, E.R., East, C.A. & Hazell, J.W. (1989b) Desferrioxamine ototoxicity: evaluation of risk factors in thalassaemic patients and guidelines for safe dosage. British Journal of Haematology 73, 403-409.
64. Porter, J.B., Morgan, J., Hoyes, K.P., Burke, L.C., Huehns, E.R. & Hider, R.C. (1990b) Relative oral efficacy and acute toxicity of hydoxypyridin-4-one iron chelators in mice. Blood, 76, 2389-2396.
65. Porter, J.B., Abeysinghe, R.D., Hoyes, K.P., Barra, C., Huehns, E.R., Brooks, P.N., Blackwell, M.P., Araneta, M., Brittenham, G., Singh, S., Dobbin, P. & Hider, R.C. (1993) Contrasting interspecies efficacy and toxicology of 1,2-diethyl-3-hydroxypyrid-4-one, CP94, relates to differing metabolism of the iron chelating site. British Journal of Haematology, 85, 159-168.
66. Porter, J.B., Abeysinghe, R.D., Marshall, L., Hider, R.C. & Singh, S. (1996) Kinetics of removal and reappearance of non-transferrin-bound plasma iron with deferoxamine therapy. Blood, 88, 705-713.
67. Porter, J.B., Kayyali, R.S. & Hider, R.C. (1997) Improved efficacy-toxicity ratios with oral iron chelators. (Abstract). 8th International Conference, Oral Chelation in the Treatment of Thalassaemia and Other Diseases, Corfu, p. 63.
68. Randell, E.W., Parkes, J.G., Olivieri, N.F. & Templeton, D.M. (1994) Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron. Journal of Biological Chemistry, 269, 16046-16053.
69. Rivkin, G., Link, G., Simhon, E., Cyjon, R.L. Klein, J. Y. & Hershko, C. (1997) IRC11. a new synthetic chelator with selective interaction with catabolic red blood cell iron: evaluation in hypertransfused rats with hepatocellular and reticuloendothelial radioiron probes and in iron-loaded rat heart cells in culture. Blood 90, 4180-4187.
70. Rothman, R.J., Serroni, A. & Farber, J.L. (1992) Cellular pool of transient ferric iron, chelatable by deferoxamine and distinct from ferritin, that is involved in oxidative cell injury. Molecular Pharmacology, 42, 703-710.
71. Schnebli, H.P., Acklin, P., Buhlmayer, P., Crowe, A., Faller, B., Jin, Y., Lattmann, P.R., Ledergerber, D., Nick, H., Sergeyew, T., Spanka, V., Tschinke, V. & Zbinden, P. (1997) Progress towards new, orally active iron chelators. (Abstract 216). Thalassaemia: 6th International Conference on Thalassaemia and the Haemoglobinopathies, St Paul's Bay, Malta.
72. Tricta, F. & Spino, M. (1997) Deferiprone: the long term cumulative experience. (Abstract). 8th International Conference. Oral Chelation in the Treatment of Thalassaemia and Other Diseases, Corfu, p. 44.
73. Tondury, P., Kontoghiorghes, G.J., Ridolfi-Luthy, A., Hirt, A., Hoffbrand, A.V., Lottenbach, A.M., Sonderegger, T. & Wagner, H.P. (1990) L1 (1.2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with beta-thalassaemia major. British Journal of Haematology, 76, 550-553.
74. Tondury, P. & Tuchschmid, P. (1997) Long-term use of deferiprone in Switzerland, 1989-1996. (Abstract 219). 6th International Conference on Thalassaemia and the Haemoglobinopathies. St Paul's Bay, Malta.
75. Tondury, P., Zimmermann, A., Nielsen, P. & Hirt, A. (1998) Liver iron and fibrosis during long-term treatment with deferiprone in Swiss thalassaemic patients. British Journal of Haematology, 101, 413-415.
76. Winchell, H.S., Klein, J.Y., Simhon, E.D., Cyjon, R.L., Klein, O. & Taklad, H. (1996) Compounds with chelation aflinity and selectivity for first transition series elements: use in medical therapy and diagnosis. Patent Cooperative Treaty (PCT) document 96/10785.
77. Ziel, R., Junker Walker, U., Pfaar, U., Vogel, B., Bentley, P. & Schnebli, H.P. (1993) Toxicological and metabolic studies with CGP 37 391 (L1). (Abstract 191). 5th International Conference on Thalassaemias and the Haemoglobinopathies, Nicosia, Cyprus.