Oral chelators deferasirox and deferiprone for transfusional iron overload in thalassemia major: New data, new questions

Blood

Volumn 107, Issue 9, 2006, Pages 3436-3441

  Neufeld, Ellis J ^a,b  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHELATING AGENT; DEFERASIROX; DEFERIPRONE; DEFEROXAMINE; DEFEROXAMINE MESYLATE;

AGRANULOCYTOSIS; ANEMIA; ARTHRALGIA; ARTHRITIS; BLOOD TRANSFUSION; CLINICAL TRIAL; DISEASE ASSOCIATION; DRUG COST; DRUG DOSE REGIMEN; DRUG EFFECT; DRUG EFFICACY; GASTROINTESTINAL TOXICITY; HEMOSIDEROSIS; HUMAN; IRON CHELATION; IRON OVERLOAD; IRON TRANSPORT; LIVER FIBROSIS; MORTALITY; NEUTROPENIA; PATIENT COMPLIANCE; PRIORITY JOURNAL; REVIEW; THALASSEMIA; THALASSEMIA MAJOR;

EID: 33646391919     PISSN: 00064971     EISSN: 00064971     Source Type: Journal    
DOI: 10.1182/blood-2006-02-002394     Document Type: Review

References (42)

1. Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with {beta}-thalassemia. Blood. 2005;107:3455-3462.
2. Borgna-Pignatti C, Cappellini MD, De Stefano P, et al. Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood. 2005;107:3733-3737.
3. Pennell DJ, Berdoukas V, Karagiorga M, et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood. 2005;107:3738-3744.
4. Davis BA, Porter JB. Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia. Blood. 2000;95:1229-1236.
5. Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004;89:1187-1193.
6. Hider RC, Zhou T. The design of orally active iron chelators. Ann N Y Acad Sci. 2005;1054:141-154.
7. Olivieri NF, Brittenham GM, McLaren CE, et al. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N Engl J Med. 1998;339:417-423.
8. Cohen AR, Galanello R, Piga A, De Sanctis V, Tricta F. Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood. 2003;102:1583-1587.
9. Hoffbrand AV, Cohen A, Hershko C. Role of deferiprone in chelation therapy for transfusional iron overload. Blood. 2003;102:17-24.
10. Taher A, Sheikh-Taha M, Sharara A, et al. Safety and effectiveness of 100 mg/kg/day deferiprone in patients with thalassemia major: a two-year study. Acta Haematol. 2005;114:146-149.
11. Hershko C, Konijn AM, Nick HP, Breuer W, Cabantchik ZI, Link G. 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. 2001;97:1115-1122.
12. Nisbet-Brown E, Olivieri NF, Giardina PJ, et al. Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet. 2003;361:1597-1602.
13. Piga A, Galanello R, Cappellini MD, et al. Phase II study of ICL670, an oral chelator, in adult thalassaemia patients with transfusional iron overload: efficacy, safety, pharmaco kinetics (PK) and pharmacodynamics (PD) after 18 months of therapy [abstract]. Blood. 2003;102:121a. Abstract 412.
14. Piga A, Galanello R, Foschini ML, et al. Oncedaily treatment with the oral iron chelator ICL670 (Exjade (R)): results of a phase II study in pediatric patients with beta-thalassemia major [abstract]. Blood. 2004;104:983a. Abstract 3614.
15. Porter J, Vichinsky E, Rose C, et al. A phase II study with ICL670 (Exjade((R))), a once-daily oral iron chelator, in patients with various transfusiondependent anemias and iron overload [abstract]. Blood. 2004;104:872a. Abstract 3193.
16. Daar S, Taher A, Pathare A, et al. Plasma LPI in beta-thalassemia patients before and after treatment with deferasirox (Exjade (R), ICL670) [abstract]. Blood. 2005;106:758a. Abstract 2697.
17. Rachmilewitz EA, Weizer-Stern O, Adamsky K, et al. Role of iron in inducing oxidative stress in thalassemia: can it be prevented by inhibition of absorption and by antioxidants? Ann N Y Acad Sci. 2005;1054:118-123.
18. Glickstein H, El RB, Shvartsman M, Cabantchik ZI. Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. Blood. 2005;106:3242-3250.
19. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood. 1997;89:739-761.
20. Anderson LJ, Holden S, Davis B, et al. Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001;22:2171-2179.
21. Pennell DJ. T2* magnetic resonance and myocardial iron in thalassemia. Ann N Y Acad Sci. 2005;1054:373-378.
22. Brittenham GM, Sheth S, Allen CJ, Farrell DE. Noninvasive methods for quantitative assessment of transfusional iron overload in sickle cell disease. Semin Hematol. 2001;38:37-56.
23. Sheth S. SQUID biosusceptometry in the measurement of hepatic iron. Pediatr Radiol. 2003;33:373-377.
24. St Pierre TG, Clark PR, Chua-anusorn W, et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood. 2005;105:855-861.
25. Brittenham GM, Nathan DG, Olivieri NF, Pippard MJ, Weatherall DJ. Deferiprone versus desferrioxamine in thalassaemia, and T2* validation and utility. Lancet. 2003;361:183; author reply 183-184.
26. Wood JC, Otto-Duessel M, Aguilar M, et al. Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy. Circulation. 2005;112:535-543.
27. Wood JC, Tyszka JM, Carson S, Nelson MD, Coates TD. Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease. Blood. 2004;103:1934-1936.
28. Westwood M, Anderson LJ, Firmin DN, et al. A single breath-hold multiecho T2* cardiovascular magnetic resonance technique for diagnosis of myocardial iron overload. J Magn Reson Imaging. 2003;18:33-39.
29. Anderson LJ, Wonke B, Prescott E, Holden S, Walker JM, Pennell DJ. Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia. Lancet. 2002;360:516-520.
30. Greenberg P, Dine G, Ganser A, et al. Deferasirox (Exjade (R), ICL670) demonstrates dose-related effects on body iron levels related to transfusional iron intake in transfusion-dependent anemia [abstract]. Blood. 2005;106:757a. Abstract 2694.
31. Cohen A, Masera G, Zoumbos N, et al. Effect of iron intake on control of body iron in patients with thalassemia major treated with deferasirox (Exjade((R)), ICL670) [abstract]. Blood. 2005;106:242a. Abstract 822.
32. Piga A, Gaglioti C, Fogliacco E, Tricta F. Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis. Haematologica. 2003;88:489-496.
33. Gomber S, Saxena R, Madan N. Comparative efficacy of desferrioxamine, deferiprone and in combination on iron chelation in thalassemic children. Indian Pediatr. 2004;41:21-27.
34. Delea TE, Sofrygin O, Thomas SK, Baladi JF, Phatak PD, Coates TD. Cost-effectiveness of once-daily oral chelation therapy with deferasirox (Exjade (R), ICL670) versus infusional deferoxamine in transfusion-dependent thalassemic patients [abstract]. Blood. 2005;106:389a. Abstract 1341.
35. Renfroe JL, Forbes P, Braunstein J, Neufeld EJ. Relationship of transfusion and iron-related complications to cost of care in thalassemia [abstract]. Blood. 2005;106:631a. Abstract 2240.
36. Delea TE, Thomas SK, Baladi JF, Phatak PD. Cost-effectiveness analysis of oral iron chelation therapy with deferasirox (Exjade (R), ICL670) versus infusional chelation therapy with deferoxamine in patients with transfusion-dependent myelodysplastic syndrome [abstract]. Blood. 2005;106:484b-485b. Abstract 5585.
37. Vichinsky E, Fischer R, Fung E, et al. A randomized, controlled phase II trial in sickle cell disease patients with chronic iron overload demonstrates that the once-daily oral iron chelator deferasirox (Exjade((R)) ICL670) is well tolerated and reduces iron burden [abstract]. Blood. 2005;106:95a. Abstract 313.
38. Porter JB, Tanner MA, Pennell DJ, Eleftheriou P. Improved myocardial T2*in transfusion dependent anemias receiving ICL670 (Deferasirox) [abstract]. Blood. 2005;106:1003a. Abstract 3600.
39. Porter J, Borgna-Pignatti C, Baccarani M, et al. Iron chelation efficiency of deferasirox (Exjade (R), ICL670) in patients with transfusional hemosiderosis [abstract]. Blood. 2005;106:755a. Abstract 2690.
40. Mourad FH, Hoffbrand AV, Sheikh-Taha M, Koussa S, Khoriaty AI, Taher A. Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients. Br J Haematol. 2003;121:187-189.
41. Link G, Konijn AM, Breuer W, Cabantchik ZI, Hershko C. Exploring the "iron shuttle" hypothesis in chelation therapy: effects of combined deferoxamine and deferiprone treatment in hypertransfused rats with labeled iron stores and in iron-loaded rat heart cells in culture. J Lab Clin Med. 2001;138:130-138.
42. Grady RW, Giardina PJ. Iron chelation: rationale for combination therapy. In: Dadman DG, Bergeron RJ, Brittenham GM, eds. Iron Chelators: New Development Strategies. Ponte Vedra Beach, FL: Saratoga; 2000:293-310.