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01-10-2005 | Review Article

Recent acquisitions in the management of iron overload

Author: Massimo Franchini

Published in: Annals of Hematology | Issue 10/2005

Abstract

Chronically transfused patients develop iron overload, which leads to organ damage and ultimately to death. The introduction of the iron-chelating agent desferrioxamine mesylate dramatically improved the life expectancy of these patients. However, the very demanding nature of this treatment (subcutaneous, continuous infusion via a battery-operated portable pump) has been the motivation for attempts to develop alternative forms of treatment that would facilitate the patients’ compliance. In this review, we describe the most important advances in iron-chelation therapy.

Borgna-Pignatti C, Rugolotto S, De Stefano P, Piga A, Di Gregorio F, Gamberini MR, Sabato V, Melevendi C, Cappellini MD, Verlato G (1998) Survival and disease complications in thalassemia major. Ann N Y Acad Sci 850:227–231

Olivieri NF (1999) The β-thalassemias. N Engl J Med 341:99–109

Gabutti V, Piga A (1996) Results of long-term iron-chelating therapy. Acta Haematol 95:26–36

Giardina PJ, Grady RW (1995) Chelation therapy in β-thalassemia: the benefits and limitations of desferrioxamine. Semin Hematol 32:304–312

Franchini M, Gandini G, Aprili G (2000) Advances in iron chelating therapy. Haematologica 85:1122–1125

Porter JB (2001) Practical management of iron overload. Br J Haematol 115:239–252

Olivieri NF, Brittenham GM (1997) Iron-chelation therapy and the treatment of thalassemia. Blood 89:739–761

Borgna-Pignatti C, Cohen A (1995) An alternative method of subcutaneous deferoxamine administration [abstract]. Blood 86(Suppl):483

Borgna-Pignatti C, Franchini M, Gandini G, Vassanelli A, de Gironcoli M, Aprili G (1998) Subcutaneous bolus injection of deferoxamine in adult patients affected by oncohematological diseases and iron overload. Haematologica 83:788–790

10.

Di Gregorio F, Romeo MA, Pizzarelli G, Aiello G, Russo G (1997) An alternative to continuous subcutaneous infusion of desferrioxamine in thalassemic patients. Br J Haematol 98:601–602

11.

Franchini M, Veneri D (2005) Recent advances in hereditary hemochromatosis. Ann Hematol 84:347–352

12.

Porter JB, Srichairatanakool S, Nathan DG, Schinkel H, Gee B, Olivieri NF (1998) Relative efficacy of subcutaneous infusion and bolus injections of deferoxamine in the removal of non-transferrin-bound iron (NTBI) [abstract]. Blood 92(Suppl):668

13.

Franchini M, Gandini G, de Gironcoli M, Vassanelli A, Borgna-Pignatti C, Aprili G (2000) Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. Blood 95:2776–2779

14.

Franchini M, Gandini G, Veneri D, Aprili G (2004) Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload: an update. Blood 103:747–748

15.

Liu DY, Liu ZD, Hider RC (2002) Oral iron chelators—development and application. Best Pract Res Clin Haematol 15:369–384

16.

Chaston TB, Richardson DR (2003) Iron chelators for the treatment of iron overload disease: relationship between structure, redox activity, and toxicity. Am J Hematol 73:200–210

17.

Hoffbrand AV, Cohen A, Hershko C (2003) Role of deferiprone in chelation therapy for transfusional iron overload. Blood 102:17–24

18.

Beutler E, Hoffbrand AV, Cook JD (2003) Iron deficiency and overload. Hematology (Am Soc Hematol Educ Program): 40–61

19.

Al-Refaie FN, Shephard LN, Nortey P, Wonke B, Hoffbrand AV (1995) Pharmacokinetics of the oral chelator deferiprone (L1) in patients with iron overload. Br J Haematol 89:403–408

20.

Shalev O, Repka T, Goldfarb A, Grinberg L, Abrahamov A, Olivieri NF, Rachmilewitz EA, Hebbel RP (1995) Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassaemic and sickle red blood cells both in vitro and in vivo. Blood 86:2008–2013

21.

Pootrakul P, Sirankapracha P, Sankote J, Kachintorn U, Maungsub W, Sriphen K, Thakernpol K, Atisuk K, Fucharoen S, Chantraluksri U, Shalev O, Hoffbrand AV (2003) Clinical trial of deferiprone iron chelation therapy in β-thalassaemia/haemoglobin E patients in Thailand. Br J Haematol 122:305–310

22.

Bartlett AN, Hoffbrand AV, Kontoghiorghes GJ (1990) Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). 2. Clinical observations. Br J Haematol 76:301–304

23.

Töndury P, Kontoghiorghes GJ, Ridolfi-Lüthy A, Hirt A, Hoffbrand AV, Lottenbach AM, Sonderegger T, Wagner HP (1990) L1 (1,2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with beta-thalassemia major. Br J Haematol 76:550–553

24.

Agarwal MB, Gupte SS, Viswanathan C, Vasandani D, Ramanathan J, Desai N, Puniyani RR, Chhablani AT (1992) Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependent thalassemia: Indian trial. Br J Haematol 82:460–466

25.

Al-Refaie FN, Hershko C, Hoffbrand AV (1995) Results of long-term deferiprone (L1) therapy: a report by the International Study Group on Oral Iron Chelators. Br J Haematol 91:224–229

26.

Olivieri NF, Brittenham GM, Matsui D, Berkovitch M, Blendis LM, Cameron RG, McClelland RA, Liu PP, Templeton DM, Koren G (1995) Iron-chelation therapy with oral deferiprone in patients with thalassemia major. N Engl J Med 332:918–922

27.

Kersten MJ, Lange R, Smeets MEP, Vreugdenhil G, Roozendaal KJ, Lameijer W, Goudsmit R (1996) Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. Ann Haematol 73:47–252

28.

Hoffbrand AV, Al-Refaie F, Davis B (1998) Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients. Blood 91:295–300

29.

Mazza P, Amurri B, Lazzari G, Masi C, Palazzo G, Spartera MA, Giua R, Sebastio AM, Suma V, De Marco S, Semeraro F, Moscogiuri R (1998) Oral iron chelating therapy. A single center interim report on deferiprone (L1) in thalassemia. Haematologica 83:496–501

30.

Olivieri NF, Brittenham GM, McLaren CE, Templeton DM, Cameron RG, McClelland RA, Burt AD, Fleming KA (1998) Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N Engl J Med 339:417–423

31.

Rombos Y, Tzanetea R, Konstantopoulos K, Simitzis S, Zervas C, Kyriaki P, Kavouklis M, Aessopos A, Sakellaropoulos N, Karagiorga M, Kalotychou V, Loukopoulos D (2000) Chelation therapy in patients with thalassemia using the orally active iron chelator deferiprone (L1). Haematologica 85:115–117

32.

Del Vecchio GC, Crollo E, Schettini F, Schettini F, Fischer R, De Mattia D (2000) Factors influencing effectiveness of deferiprone in a thalassemia major clinical setting. Acta Haematol 104:99–102

33.

Taher A, Sheik-Taha M, Koussa S, Inati A, Neeman R, Mourad F (2001) Comparison between deferoxamine and deferiprone (L1) in iron-loaded thalassemia patients. Eur J Haematol 67:30–34

34.

Maggio A, D’Amico G, Morabito A, Capra M, Ciaccio C, Cianciulli P, Di Gregorio F, Garozzo G, Malizia R, Magnano C, Mangiagli A, Quarta G, Rizzo M, D’Ascola DG, Rizzo A, Midiri M (2002) Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial. Blood Cells Mol Dis 28:196–208

35.

Ceci A, Baiardi P, Felisi M (2002) The safety and effectiveness of deferiprone in a large-scale, 3-year study in Italian patients. Br J Haematol 118:330–336

36.

Cohen AR, Galanello R, Piga A, De Sanctis V, Tricta F (2003) Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood 102:1583–1587

37.

Naithani R, Chandra J, Sharma S (2005) Safety of oral iron chelator deferiprone in young thalassaemics. Eur J Haematol 74:217–220

38.

Addis A, Lochstein R, Koren G, Einarson TR (1999) Meta-analytic review of the clinical effectiveness of oral deferiprone (L1). Eur J Clin Pharmacol 55:1–6

39.

Franchini M, Veneri D (2004) Iron-chelation therapy: an update. Hematol J 5:287–292

40.

Fischer R, Longo F, Nielsen P, Engelhardt R, Hider RC, Piga A (2003) Monitoring long-term efficacy of iron chelation therapy by deferiprone and desferrioxamine in patients with beta-thalassaemia major: application of SQUID biomagnetic liver susceptometry. Br J Haematol 121:938–948

41.

Anderson LJ, Wonke B, Prescott E, Holden S, Walker JM, Pennel DJ (2002) Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia. Lancet 360:516–520

42.

Piga A, Gaglioti C, Fogliacco E, Tricta F (2003) Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis. Haematologica 88:489–496

43.

Hershko C, Cappellini MD, Galanello R, Piga A, Tognoni G, Masera G (2004) Purging iron from the heart. Br J Haematol 125:545–551

44.

Cohen AR, Galanello R, Piga A, DiPalma A, Vullo C, Tricta F (2000) Safety profile of the oral iron chelator deferiprone: a multicenter study. Br J Haematol 108:305–312

45.

Grady RW, Giardina PJ (1998) Iron chelation with oral deferiprone in patients with thalassemia [letter]. N Engl J Med 339:1712–1713

46.

Wanless IR, Sweeney G, Dhillon AP, Guido M, Piga A, Galanello R, Gamberini MR, Schwartz E, Cohen AR (2002) Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia. Blood 100:1566–1569

47.

Tondury P, Zimmermann A, Nielsen P, Hirt A (1998) Liver iron and fibrosis during long-term treatment with deferiprone in Swiss thalassaemic patients. Br J Haematol 101:413–415

48.

Kwiatkowski JL, Cohen AR (2004) Iron chelation therapy in sickle-cell disease and other transfusion-dependent anemias. Hematol Oncol Clin N Am 18:1355–1377

49.

Hershko C, Konijn AM, Nick HP, Breuer V, Cabantchik ZI, Link G (2001) ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture. Blood 97:1115–1122

50.

Galanello R, Piga A, Alberti D, Rouan MC, Bigler H, Séchaud R (2003) Safety, tolerability and pharmacokinetics of ICL670, a new orally active iron-chelating agent in patients with transfusion-dependent iron overload due to β-thalassemia. J Clin Pharmacol 43:565–572

51.

Nisbet-Brown E, Olivieri NF, Giardina PJ, Grady RW, Neufeld EJ, Sechaud R, Krebs-Brown AJ, Anderson JR, Alberti D, Sizer KC, Nathan DG (2003) Effectiveness and safety of ICL670 in iron-loaded patients with thalassemia: a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 361:1597–1602

52.

Piga A, Galanello R, Cappellini MD, Forni G-L, Lupo G, Ford JM (2003) Phase II study of ICL670, an oral chelator, in adult thalassemia patients with transfusional iron overload: efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) after 18 months of therapy. Blood 102:121a

53.

Cohen AR, Galanello R, Pennell DJ, Cunningham MJ, Vichinsky E (2004) Thalassemia. Hematology (Am Soc Hematol Educ Program) :14–34

54.

Hershko C, Link G, Konijn AM, Cabantchik ZI (2005) Iron chelation therapy. Curr Hematol Rep 4:110–116

55.

Wonke B, Wright C, Hoffbrand AV (1998) Combined therapy with deferiprone and desferrioxamine. Br J Haematol 103:361–364

56.

Balveer K, Pyar K, Wonke B (2000) Combined oral and parenteral iron chelation in beta thalassaemia major. Med J Malays 55:493–497

57.

Aydinok Y, Nisli G, Kavakli K (1999) Sequential use of deferiprone and desferrioxamine in primary school children with thalassemia major in Turkey. Acta Haematol 102:17–21

58.

Alymara V, Bourantas DK, Chaidos A (2002) Combined iron chelation therapy with desferrioxamine and deferiprone in β-thalassemic patients. Hematol J 3(Suppl 1):81

59.

Kattamis A, Kassou C, Ladis V (2002) Safety and efficacy of combining deferiprone and deferoxamine in iron chelation therapy in patients with thalassemia. Blood 100:11

60.

Mourad FH, Hoffbrand AV, Sheik-Taha M, Koussa S (2003) Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassemia patients. Br J Haematol 121:187–189

61.

Grady RW, Berdoukas V, Rachmilewitz EA (2002) Combination of desferrioxamine and deferiprone markedly enhance iron excretion. Blood 100:241a

62.

Breuer W, Ermers MJ, Pootrakul P, Abramov A, Hershko C, Cabantchik ZI (2001) Desferrioxamine-chelatable iron, a component of serum non-transferrin-bound iron, used for assessing chelation therapy. Blood 97:792–798

63.

Ponka P, Borova J, Neuwirt J, Fuchs O, Necas E (1979) A study of intracellular iron metabolism using pyridoxal isonicotinoyl hydrazone and other synthetic chelating agents. Biochim Biophys Acta 586:278–297

64.

Richardson DR, Ponka P (1998) Pyridoxal isonicotinoyl hydrazone and its analogs: potential orally effective iron-chelating agents for the treatment of iron overload disease. J Lab Clin Med 131:306–315

65.

Brittenham GM (1990) Pyridoxal isonicotinoyl hydrazone: an effective iron-chelator after oral administration. Semin Hematol 27:112–116

66.

Link G, Ponka P, Konijn AM, Breuer W, Cabantchik ZI, Hershko C (2003) Effects of combined chelation treatment with pyridoxal isonicotinoyl hydrazone analogs and deferoxamine in hypertransfused rats and in iron-loaded rat heart cells. Blood 101:4172–4179

67.

Grady RW, Salbe AD, Hilgartner MW, Giardina PJ (1994) Results from a phase I clinical trial of HBED. Adv Exp Med Biol 356:351–359

68.

Bergeron RJ Wiegand J, Brittenham GM (2002) HBED ligand: preclinical studies of a potential alternative to deferoxamine for treatment of chronic iron overload and acute iron poisoning. Blood 99:3019–3026

Title: Recent acquisitions in the management of iron overload
Author: Massimo Franchini
Publication date: 01-10-2005
Publisher: Springer-Verlag
Published in: Annals of Hematology / Issue 10/2005
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-005-1083-8

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