Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major

New England Journal of Medicine

Volumn 339, Issue 7, 1998, Pages 417-423

  Olivieri, Nancy F ^a,g   Brittenham, Gary M ^c   Mclaren, Christine E ^d   Templeton, Douglas M ^b   Cameron, Ross G ^b   Mcclelland, Robert A ^a   Burt, Alastair D ^e   Fleming, Kenneth A ^f  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c New York Presbyterian Columbia University Medical Center   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e ROYAL VICTORIA INFIRMARY   (United Kingdom)

^f UNIVERSITY OF OXFORD   (United Kingdom)

^g HOSPITAL FOR SICK CHILDREN   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CHELATING AGENT; DEFERIPRONE; DEFEROXAMINE; IRON;

ADOLESCENT; ADULT; ARTICLE; CHILD; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED STUDY; DRUG EFFICACY; DRUG SAFETY; FEMALE; HUMAN; IRON CHELATION; LIVER BIOPSY; LIVER FIBROSIS; LONG TERM CARE; MALE; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; THALASSEMIA MAJOR;

ADOLESCENT; ADULT; BETA-THALASSEMIA; BIOPSY; CHILD; DEFEROXAMINE; DISEASE PROGRESSION; FEMALE; HUMANS; IRON; IRON CHELATING AGENTS; IRON OVERLOAD; LIVER; LIVER CIRRHOSIS; LOGISTIC MODELS; MALE; PYRIDONES; TREATMENT FAILURE;

EID: 0032514558     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJM199808133390701     Document Type: Article

References (34)

1. Cooley's Anemia Progress Review Committee. Cooley's anemia: progress in biology and medicine. Bethesda, Md.: Division of Blood Diseases and Resources, 1995.
2. Fosburg MT, Nathan DG. Treatment of Cooley's anemia. Blood 1990; 76:435-44.
3. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood 1997;89:739-61. [Erratum, Blood 1997;89:2621.]
4. Bergeron RJ, Brittenham GM, eds. Development of iron chelators for clinical use. Boca Raton, Fla.: CRC Press, 1994.
5. Kontoghiorghes GJ, Aldouri MA, Sheppard LN, Hoffbrand AV. 1,2-dimethyl-3-hydroxypyrid-4-one, an orally active chelator for treatment of iron overload. Lancet 1987;1:1294-5.
6. Kontoghiorghes GJ, Bartlett AN, Hoffbrand AV, et al. Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). I. Iron chelation and metabolic studies. Br J Haematol 1990;76:295-300.
7. al-Refaie FN, Wonke B, Hoffbrand AV, Wickens DG, Nortey P, Kontoghiorghes GJ. Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in thalassemia major. Blood 1992;80:593-9.
8. al-Refaie FN, Hershko C, Hoffbrand AV, et al. Results of long-term deferiprone (L1) therapy: a report by the International Study Group on Oral Iron Chelators. Br J Haematol 1995;91:224-9.
9. Olivieri NF, Koren G, Hermann C, et al. Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients. Lancet 1990;336: 1275-9.
10. Tondury P, Kontoghiorghes GJ, Ridolfi-Luthy AR, et al. L1 (1,2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with beta-thalassaemia major. Br J Haematol 1990;76:550-3.
11. Agarwal MB, Gupte 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;82:460-6.
12. Olivieri NF, Brittenham GM, Matsui D, et al. Iron-chelation therapy with oral deferiprone in patients with thalassemia major. N Engl J Med 1995;332:918-22.
13. Carthew P, Smith AG, Hider RC, Dorman B, Edwards RE, Francis JE. Potentiation of iron accumulation in cardiac myocytes during the treatment of iron overload in gerbils with the hydroxypyridinone iron chelator CP94. Biometals 1994;7:267-71.
14. Brittenham GM, Farrell DE, Harris JW, et al. Magnetic-susceptibility measurement of human iron stores. N Engl J Med 1982;307:1671-5.
15. Overmoyer BA, McLaren CE, Brittenham GM. Uniformity of liver density and nonheme (storage) iron distribution. Arch Pathol Lab Med 1987;111:549-54.
16. Wong A, Alder V, Robertson D, et al. Liver iron depletion and toxicity of the iron chelator deferiprone (L1, CP20) in the guinea pig. Biometals 1997;10:247-56.
17. Brittenham GM, Griffith PM, Nienhuis AW, et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 1994;331:567-73.
18. Olivieri NF, Nathan DG, MacMillan JH, et al. Survival in medically treated patients with homozygous β-thalassemia. N Engl J Med 1994;331:574-8.
19. Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995;22:696-9.
20. Cramer JA, Mattson RH, Prevey ML, Scheyer RD, Ouellette VL. How often is medication taken as prescribed? A novel assessment technique. JAMA 1989;261:3273-7. [Erratum, JAMA 1989;262:1472.]
21. Fleiss JL. Statistical methods for rates and proportions. 2nd ed. New York: John Wiley, 1981.
22. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
23. Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 1977;35:1-39.
24. Hoffbrand AV, Al-Refaie F, Davis B, et al. Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients. Blood 1998; 91:295-300.
25. Barry M, Flynn DM, Letsky EA, Risdon RA. Long-term chelation therapy in thalassaemia major: effect on liver iron concentration, liver histology and clinical progress. BMJ 1974;2:16-20.
26. Risdon RA, Flynn DM, Barry M. The relation between liver iron concentration and liver damage in transfusional iron overload in thalassaemia and the effect of chelation therapy. Gut 1973;14:421.
27. Risdon RA, Barry M, Flynn DM. Transfusional iron overload: the relationship between tissue iron concentration and hepatic fibrosis in thalassaemia. J Pathol 1975;116:83-95.
28. Aldouri MA, Wonke B, Hoffbrand AV, et al. Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine. J Clin Pathol 1987;40:1353-9.
29. Halliwell B. Drug antioxidant effects: a basis for drug selection? Drugs 1991;42:569-605.
30. Halliwell B. Iron, oxidative damage, and chelating agents. In: Bergeron RJ Brittenham GM, eds. Development of iron chelators for clinical use. Boca Raton, Fla.: CRC Press, 1994:33-56.
31. Nathan DG. An orally active iron chelator. N Engl J Med 1995;332: 953-4. [Erratum, N Engl J Med 1995;332:1315.]
32. Motekitis RJ, Martell AE. Stabilization of the iron (III) chelates of 1,2-dimethyl-3-hydroxypyrid-4-ones and related ligands. Inorg Chim Acta 1991;183:71-80.
33. Cragg L, Hebbel RP, Solovey A, Miller WJ, Enright H. The iron chelator L1 potentiates iron-mediated oxidative DNA damage. Blood 1996; 88:Suppl 1:646a. abstract.
34. Hershko C, Link G, Pinson A, Konijn AM. Deferiprone (L1) fails to mobilize iron and promotes iron cardiotoxicity at suboptimal L1/iron concentrations. Blood 1997;90:Suppl 1:11a. abstract.