Optimal management strategies for chronic iron overload

Drugs

Volumn 67, Issue 5, 2007, Pages 685-700

  Barton, James C ^a  

^a SOUTHERN IRON DISORDERS CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASCORBIC ACID; DEFERASIROX; DEFERIPRONE; DEFEROXAMINE; DEFEROXAMINE MESYLATE; HEMOGLOBIN; IRON;

ABDOMINAL PAIN; AGRANULOCYTOSIS; AMINOTRANSFERASE BLOOD LEVEL; ARTHRALGIA; BETA THALASSEMIA; CATARACT; CHELATION THERAPY; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CREATININE BLOOD LEVEL; CYTAPHERESIS; DIAGNOSTIC TEST; DIARRHEA; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG EXCRETION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; GASTROINTESTINAL SYMPTOM; GROWTH RETARDATION; HEARING IMPAIRMENT; HEARING LOSS; HEMOCHROMATOSIS; HUMAN; HYPOVOLEMIA; INFECTION; INJECTION SITE PAIN; INTRAOCULAR PRESSURE ABNORMALITY; IRON ABSORPTION; IRON DEFICIENCY; IRON OVERLOAD; IRON THERAPY; KIDNEY FAILURE; LIVER BIOPSY; LIVER CIRRHOSIS; MONOTHERAPY; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; PATIENT COMPLIANCE; PHLEBOTOMY; PROPHYLAXIS; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RASH; RETINA DISEASE; RETINA INJURY; REVIEW; SICKLE CELL ANEMIA; SIDE EFFECT; SIDEROSIS; SKELETON MALFORMATION; VISUAL IMPAIRMENT; ZINC DEFICIENCY;

CHRONIC DISEASE; ERYTHROCYTE TRANSFUSION; HUMANS; IRON CHELATING AGENTS; IRON OVERLOAD; PHLEBOTOMY;

EID: 34047214190     PISSN: 00126667     EISSN: 00126667     Source Type: Journal    
DOI: 10.2165/00003495-200767050-00004     Document Type: Review

References (149)

1. Porter JB. Practical management of iron overload. Br J Haematol 2001; 115: 239-52
2. Kushner JP, Porter JP, Olivieri NF. Secondary iron overload. Hematology Am Soc Hematol Educ Program 2001, 47-61
3. Schafer AI, Cheron RG, Dluhy R, et al. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med 1981; 304: 319-24
4. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996; 13: 399-408
5. Beutler E, Hoffbrand AV, Cook JD. Iron deficiency and overload. Hematology Am Soc Hematol Educ Program 2003, 40-61
6. Gordeuk V, Mukiibi J, Hasstedt SJ, et al. Iron overload in Africa: interaction between a gene and dietary iron content. N Engl J Med 1992; 326: 95-100
7. Barton JC, Acton RT, Rivers CA, et al. Genotypic and phenotypic heterogeneity of African Americans with primary iron overload. Blood Cells Mol Dis 2003; 31: 310-9
8. Beutler E, Barton JC, Felitti VJ, et al. Ferroportin 1 (SCL40A1) variant associated with iron overload in African-Americans. Blood Cells Mol Dis 2003; 31: 305-9
9. Jaeger M, Aul C, Sohngen D, et al. Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes [in German]. Beitr Infusionsther 1992; 30: 464-8
10. Gattermann N. Clinical consequences of iron overload in myelodysplastic syndromes and treatment with chelators. Hematol Oncol Clin 2005; 19 Suppl. 1: 13-7
11. Vassiliadis T, Garipidou V, Perifanis V, et al. A case of successful management with splenectomy of intractable ascites due to congenital dyserythropoietic anemia type II-induced cirrhosis. World J Gastroenterol 2006; 12: 818-21
12. Halpern Z, Rahmani R, Levo Y. Severe hemochromatosis: the predominant clinical manifestation of congenital dyserythropoietic anemia type 2. Acta Haematol 1985; 74: 178-80
13. Bett JH, Wilkinson RK, Boyle CM. Iron overload associated with congenital pyruvate kinase deficiency and high dose ascorbic acid ingestion [letter]. Aust N Z J Med 1985; 15: 270
14. Barton JC, Lee PL, West C, et al. Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis-associated genes in four cases. Am J Hematol 2006; 81: 760-7
15. 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
16. Ceci A, Baiardi P, Cataprano M, et al. Risk factors for death in patients with β-thalassemia major: results of a case-control study. Haematologica 2006; 91: 1420-1
17. Borgna-Pignatti C, Cappellini MD, De Stefano P, et al. Survival and complications in thalassemia. Ann N Y Acad Sci 2005; 1054: 40-7
18. Witte DL, Crosby WH, Edwards CQ, et al. Practice guideline development task force of the College of American Pathologists. Hereditary hemochromatosis. Clin Chim Acta 1996; 245: 139-200
19. Wu KH, Tsai FJ, Peng CT. Growth hormone (GH) deficiency in patients with beta-thalassemia major and the efficacy of reders combinant GH treatment. Ann Hematol 2003; 82: 637-40
20. De Sanctis V, Roos M, Gasser T, et al. Impact of long-term iron chelation therapy on growth and endocrine functions in thalassaemia. J Pediatr Endocrinol Metab 2006; 19: 471-80
21. Barton JC, McDonnell SM, Adams PC, et al. Management of hemochromatosis. Hemochromatosis Management Working Group. Ann Intern Med 1998; 129: 932-9
22. Carneiro AA, Vilela GR, Fernandes JB, et al. In vivo tissue characterization using magnetic techniques [abstract]. Neurol Clin Neurophysiol 2004; 2004: 85
23. Fischer R, Harmatz P, Nielsen P. Does liver biopsy overestimate liver iron concentration? Blood 2006; 108: 1775-6
24. Brittenham GM, Badman DG. Noninvasive measurement of iron: report of an NIDDK workshop. Blood 2003; 101: 15-9
25. Wood JC, Enriquez C, Ghugre N, et al. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 2005; 106: 1460-5
26. Butensky E, Fischer R, Hudes M, et al. Variability in hepatic iron concentration in percutaneous needle biopsy specimens from patients with transfusional hemosiderosis. Am J Clin Pathol 2005; 123: 146-52
27. 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: 855-61
28. Kellner H, Zoller WG. Repeated isovolemic large-volume erythrocytapheresis in the treatment of idiopathic hemochromatosis. Z Gastroenterol 1992; 30: 779-83
29. de Alarcon PA, Donovan ME, Forbes GB, et al. Iron absorption in the thalassemia syndromes and its inhibition by tea. N Engl J Med 1979; 300: 5-8
30. Kaltwasser JP, Werner E, Schalk K, et al. Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis. Gut 1998; 43: 699-704
31. Collins AF, Fassos FF, Stobie S, et al. Iron-balance and dose-response studies of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron-loaded patients with sickle cell disease. Blood 1994; 83: 2329-33
32. Pippard MJ, Callender ST, Finch CA. Ferrioxamine excretion in iron-loaded man. Blood 1982; 60: 288-94
33. Hershko C, Link G, Konijn AM. Chelation therapy in iron overload. In: Barton JC, Edwards CQ, editors. Hemochromatosis: genetics, pathophysiology, diagnosis and treatment. Cambridge: Cambridge University Press, 2000: 339-54
34. Gabutti V, Piga A. Results of long-term iron-chelating therapy. Acta Haematol 1996; 95: 26-36
35. Araujo A, Kosaryan M, MacDowell A, et al. A novel delivery system for continuous desferrioxamine infusion in transfusional iron overload. Br J Haematol 1996; 93: 835-7
36. Borgna-Pignatti C, Cohen A. Evaluation of a new method of administration of the iron chelating agent deferoxamine. J Pediatr 1997; 130: 86-8
37. Davis BA, Porter JB. Results of long term iron chelation treatment with deferoxamine. Adv Exp Med Biol 2002; 509: 91-125
38. Anderson LJ, Wonke B, Prescott E, et al. Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in betathalassaemia. Lancet 2002; 360: 516-20
39. Liu DY, Liu ZD, Hider RC. Oral iron chelators: development and application. Best Pract Res Clin Haematol 2002; 15: 369-84
40. Shalev O, Repka T, Goldfarb A, et al. Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle red blood cells both in vitro and in vivo. Blood 1995; 86: 2008-13
41. Pootrakul P, Sirankapracha P, Sankote J, et al. Clinical trial of deferiprone iron chelation therapy in beta-thalassaemia/haemoglobin E patients in Thailand. Br J Haematol 2003; 122: 305-10
42. Agarwal MB, Gupte SS, Vasandani D, et al. Efficacy and safety of 1-2, dimethyl-3-hydroxypyrid-4-one (L1) as an oral iron chelator in patients of beta thalassaemia major with iron overload. J Assoc Physicians India 1991; 39: 669-72
43. Kontoghiorghes GJ, Aldouri MA, Sheppard L, et al. 1,2-Dimethyl-3- hydroxypyrid-4-one, an orally active chelator for treatment of iron overload. Lancet 1987; I: 1294-5
44. Olivieri NF, Brittenham GM, Matsui D, et al. Iron-chelation therapy with oral deferipronein patients with thalassemia major. N Engl J Med 1995; 332: 918-22
45. al Refaie FN, Sheppard LN, Nortey P, et al. Pharmacokinetics of the oral iron chelator deferiprone (L1) in patients with iron overload. Br J Haematol 1995; 89: 403-8
46. Cohen AR, Galanello R, Piga A, et al. Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood 2003; 102: 1583-7
47. Ceci A, Baiardi P, Felisi M, et al. The safety and effectiveness of deferiprone in a large-scale, 3-year study in Italian patients. Br J Haematol 2002; 118: 330-6
48. 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: 417-23
49. Wanless IR, Sweeney G, Dhillon AP, et al. Lack of progressive develhepatic fibrosis during long-term therapy with deferiprone in hemochrosubjects with transfusion-dependent beta-thalassemia. Blood 2002; 100: 1566-9
50. Barton JC. Deferasirox Novartis. Curr Opin Investig Drugs 2005; 6: 327-35
51. Cappellini MD. Iron-chelating therapy with the new oral agent ICL670 (Exjade). Best Pract Res Clin Haematol 2005; 18: 289-98
52. Galanello R, Piga A, Alberti D, et al. Safety, tolerability, and pharmacokinetics of ICL670, a new orally active iron-chelating agent in patients with transfusion-dependent iron overload due to beta-thalassemia. J Clin Pharmacol 2003; 43: 565-72
53. Piga A, Galanello R, Foschini ML, et al. Once-daily treatment with the oral iron chelator ICL670 (Exjade): results of a phase II study in pediatric patients with beta-thalassemia major. Blood 2004, 104
54. Piga A, Galanello R, Forni GL, et al. Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload. Haematologica 2006; 91: 873-80
55. Porter J, Vichinsky E, Rose C, et al. A phase II study with ICL670 (Exjade), a once-daily oral iron chelator, in patients with various transfusion-dependent anemias and iron overload [abstract]. Blood 2004; 104: 872a
56. Vanorden HE, Hagemann TM. Deferasirox: an oral agent for chronic iron overload. Ann Pharmacother 2006; 40: 1110-7
57. Glickstein H, El RB, Shvartsman M, et al. Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. Blood 2005; 106: 3242-50
58. Glickstein H, El RB, Link G, et al. Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences. Blood 2006; 108: 3195-203
59. Piga A, Galanello R, Cappelini MD, et al. Phase II study of oral chelator ICL670 in thalassaemia patients with transfusional iron overload: efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) after 6 months of therapy [abstract]. Blood 2002; 100: 5a
60. 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: 1597-602
61. 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 2006; 107: 3455-62
62. Bomford A, Williams R. Long term results of venesection therapy in idiopathic haemochromatosis. Q J Med 1976; 45: 611-23
63. McLaren CE, Barton JC, Adams PC, et al. Hemochromatosis and Iron Overload Screening (HEIRS) study design for an evaluation of 100,000 primary care-based adults. Am J Med Sci 2003; 325: 53-62
64. Bolan CD, Conry-Cantilena C, Mason G, et al. MCV as a guide to phlebotomy therapy for hemochromatosis. Transfusion 2001; 41: 819-27
65. Hicken BL, Tucker DC, Barton JC. Patient compliance with phlebotomy therapy for iron overload associated with hemochromatosis. Am J Gastroenterol 2003; 98: 2072-7
66. Conte D, Mandelli C, Cesana M, et al. Effectiveness of erythrocytapheresis in idiopathic hemochromatosis: report of 14 cases. Int J Artif Organs 1989; 12: 59-62
67. Fraquelli M, Mandelli C, Cesarini L, et al. Survival and development of neoplasms in 56 patients with idiopathic hemochromatosis [in Italian]. Ann Ital Med Int 1992; 7: 26-9
68. Kohan A, Niborski R, Daruich J, et al. Erythrocytapheresis with recombinant human erythropoietin in hereditary hemochromatosis therapy: a new alternative. Vox Sang 2000; 79: 40-5
69. Mariani R, Pelucchi S, Perseghin P, et al. Erythrocytapheresis plus erythropoietin: an alternative therapy for selected patients with hemochromatosis and severe organ damage. Haematologica 2005; 90: 717-8
70. Cesana M, Mandelli C, Tiribelli C, et al. Concomitant primary hemochromatosis and beta-thalassemia trait: iron depletion by erythrocytapheresis and desferrioxamine. Am J Gastroenterol 1989; 84: 150-2
71. Fabio G, Minonzio F, Delbini P, et al. Reversal of cardiac complications by deferiprone and deferoxamine combination therapy in a patient affected by severe type of juvenile hemochromatosis (JH). Blood 2007; 109: 362-4
72. Wohler F. The treatment of haemochromatosis with desferrioxamine. Acta Haematol 1963; 30: 65-87
73. Speight AN, Cliff J. Iron storage disease of the liver in Dar es Salaam: a preliminary report on venesection therapy. East Afr Med J 1974; 51: 895-902
74. Kattamis A, Papassotiriou I, Palaiologou D, et al. The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica 2006; 91: 809-12
75. Efthimiadis GK, Hassapopoulou HP, Tsikaderis DD, et al. Survival in thalassaemia major patients. Circ J 2006; 70: 1037-42
76. Tanner MA, Galanello R, Dessi C, et al. Myocardial iron loading in patients with thalassemia major on deferoxamine chelation. J Cardiovasc Magn Reson 2006; 8: 543-7
77. Borgna-Pignatti C, Cappellini MD, De Stefano P, et al. Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood 2006; 107: 3733-7
78. Borgna-Pignatti C, Vergine G, Lombardo T, et al. Hepatocellular carcinoma in the thalassaemia syndromes. Br J Haematol 2004; 124: 114-7
79. 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: 2171-9
80. Anderson LJ, Westwood MA, Prescott E, et al. Development of thalassaemic iron overload cardiomyopathy despite low liver iron levels and meticulous compliance to desferrioxamine. Acta Haematol 2006; 115: 106-8
81. Aldouri MA, Wonke B, Hoffbrand AV, et al. High incidence of cardiomyopathy in beta-thalassaemia patients receiving regular transfusion and iron chelation: reversal by intensified chelation. Acta Haematol 1990; 84: 113-7
82. Olivieri NF, Nathan DG, MacMillan JH, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994; 331: 574-8
83. Modell B, Khan M, Darlison M. Survival in beta-thalassaemia major in the UK: data from the UK Thalassaemia Register. Lancet 2000; 355: 2051-2
84. Piga A, Gaglioti C, Fogliacco E, et al. Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis. Haematologica 2003; 88: 489-96
85. Maggio A, D'Amico G, Morabito A, et al. Deferiprone versus deferoxamine in patients with thalassemia major: a randomsion ized clinical trial. Blood Cells Mol Dis 2002; 28: 196-208
86. 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 2006; 107: 3738-44
87. Hoffbrand AV, Cohen A, Hershko C. Role of deferiprone in chelation therapy for transfusional iron overload. Blood 2003; 102: 17-24
88. Fischer R, Longo F, Nielsen P, et al. 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 2003; 121: 938-48
89. Wonke B, Wright C, Hoffbrand AV. Combined therapy with deferiprone and desferrioxamine. Br J Haematol 1998; 103: 361-4
90. Origa R, Bina P, Agus A, et al. Combined therapy with deferiprone and desferrioxamine in thalassemia major. Haematologica 2005; 90: 1309-14
91. D'Angelo E, Mirra N, Rocca A, et al. Combined therapy with desferrioxamine and deferiprone: a new protocol for iron cheamine. lation in thalassemia. J Pediatr Hematol Oncol 2004; 26: 451-3
92. Kolnagou A, Kontoghiorghes GJ. Effective combination therapy of deferiprone and deferoxamine for the rapid clearance of excess cardiac IRON and the prevention of heart disease in thalassemia. The Protocol of the International Committee on Oral Chelators. Hemoglobin 2006; 30: 239-49
93. Galanello R, Kattamis A, Piga A, et al. A prospective randomized controlled trial on the safety and efficacy of alternating deferoxamine and deferiprone in the treatment of iron overload in patients with thalassemia. Haematologica 2006; 91: 1241-3
94. Wu KH, Chang JS, Tsai CH, et al. Combined therapy with deferiprone and desferrioxamine successfully regresses severe heart failure in patients with beta-thalassemia major. Ann Hematol 2004; 83: 471-3
95. Tavecchia L, Masera N, Russo P, et al. Successful recovery of acute hemosiderotic heart failure in beta-thalassemia major treated with a combined regimen of desferrioxamine and deferiprone. Haematologica 2006; 91: ECR19
96. Telfer P, Coen PG, Christou S, et al. Survival of medically treated thalassemia patients in Cyprus: trends and risk factors over the period 1980-2004. Haematologica 2006; 91: 1187-92
97. Olivieri NF, Koren G, Matsui D, et al. Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. Blood 1992; 79: 2741-8
98. Kearney SL, Nemeth E, Neufeld EJ, et al. Urinary hepcidin in congenital chronic anemias. Pediatr Blood Cancer 2007; 48: 57-63
99. Barton JC, Lee PL, Bertoli LF, et al. Iron overload in an African American woman with SS hemoglobinopathy and a promoter mutation in the X-linked erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. Blood Cells Mol Dis 2005; 34: 226-8
100. Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 1998; 91: 288-94
101. Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med 1998; 339: 5-11
102. Adams RJ, Brambilla DJ, Granger S, et al. Stroke and conversion to high risk in children screened with transcranial Doppler ultrasound during the STOP study. Blood 2004; 103: 3689-94
103. Lee MT, Piomelli S, Granger S, et al. Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results. Blood 2006; 108: 847-52
104. Darbari DS, Kple-Faget P, Kwagyan J, et al. Circumstances of death in adult sickle cell disease patients. Am J Hematol 2006; 81: 858-63
105. Ballas SK. Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol 2001; 38: 30-6
106. Adams DM, Schultz WH, Ware RE, et al. Erythrocytapheresis can reduce iron overload and prevent the need for chelation therapy in chronically transfused pediatric patients. J Pediatr Hematol Oncol 1996; 18: 46-50
107. Hartwig D, Schlager F, Bucsky P, et al. Successful long-term erythrocytapheresis therapy in a patient with symptomatic sickle-cell disease using an arterio-venous fistula. Transfus Med 2002; 12: 75-7
108. Hilliard LM, Williams BF, Lounsbury AE, et al. Erythrocytapheresis limits iron accumulation in chronically transfused sickle cell patients. Am J Hematol 1998; 59: 28-35
109. Kim HC, Dugan NP, Silber JH, et al. Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease. Blood 1994; 83: 1136-42
110. Singer ST, Quirolo K, Nishi K, et al. Erythrocytapheresis for chronically transfused children with sickle cell disease: an effective method for maintaining a low hemoglobin S level and reducing iron overload. J Clin Apher 1999; 14: 122-5
111. Raj AB, Condurache T, Bertolone S, et al. Quantitative assessment of ventricular function in sickle cell disease: effect of long-term erythrocytapheresis. Pediatr Blood Cancer 2005; 45: 976-81
112. Cohen A, Schwartz E. Excretion of iron in response to deferoxamine in sickle cell anemia. J Pediatr 1978; 92: 659-62
113. Pippard MJ. Iron overload and iron chelation therapy in thalassaemia and sickle cell haemoglobinopathies. Acta Haematol 1987; 78: 206-11
114. Treadwell MJ, Weissman L. Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy. Semin Hematol 2001; 38: 77-84
115. Treadwell MJ, Law AW, Sung J, et al. Barriers to adherence of deferoxamine usage in sickle cell disease. Pediatr Blood Cancer 2005; 44: 500-7
116. Shalev O, Hileti D, Nortey P, et al. Transport of 14C-deferiprone in normal, thalassaemic and sickle red blood cells. Br J Haematol 1999; 105: 1081-3
117. Voskaridou E, Douskou M, Terpos E, et al. Deferiprone as an oral iron chelator in sickle cell disease. Ann Hematol 2005; 84: 434-40
118. Okpala I. Investigational agents for sickle cell disease. Expert Opin Investig Drugs 2006; 15: 833-42
119. Williamson PJ, Kruger AR, Reynolds PJ, et al. Establishing the incidence of myelodysplastic syndrome. Br J Haematol 1994; 87: 743-5
120. List AF. New approaches to the treatment of myelodysplasia. Oncologist 2002; 7 Suppl. 1: 39-49
121. Bowen D. What is ineffective erythropoiesis in myelodysplastic syndromes? Leuk Lymphoma 1995; 18: 243-7
122. Rose C, Cambier N, Mahieu M, et al. Iron overload and myprogram. elodysplastic syndromes [in French]. Transfus Clin Biol 2001; 8: 422-32
123. Malcovati L, Porta MG, Pascutto C, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005; 23: 7594-603
124. Barton JC, Bertoli LF, Acton RT. HFE C282Y and H63D in adults with malignancies in a community medical oncology practice. BMC Cancer 2004; 4: 6
125. Varkonyi J, Tarkovacs G, Karadi I, et al. High incidence of hemochromatosis gene mutations in the myelodysplastic syndrome: the Budapest Study on 50 patients. Acta Haematol 2003; 109: 64-7
126. Hannuksela J, Savolainen ER, Koistinen P, et al. Prevalence of HFE genotypes, C282Y and H63D, in patients with hematocan logic disorders. Haematologica 2002; 87: 131-5
127. Greenberg PL, Baer MR, Bennett JM, et al. Myelodysplastic syndromes clinical practice guidelines in oncology. J Natl Compr Canc Netw 2006; 4: 58-77
128. Borgna-Pignatti C, Franchini M, Gandini G, et al. Subcutaneous bolus injection of deferoxamine in adult patients affected by onco-hematologic diseases and iron overload. Haematologica 1998; 83: 788-90
129. Del Rio GJ, Fernandez LC, Batlle Fonrodona FJ. Desferrioxamine in the treatment of myelodysplastic syndromes. Haematologica 1997; 82: 639-40
130. Jensen PD, Heickendorff L, Pedersen B, et al. The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. Br J Haematol 1996; 94: 288-99
131. Jiang Y, Xue ZH, Shen WZ, et al. Desferrioxamine induces leukemic cell differentiation potentially by hypoxia-inducible factor-1 alpha that augments transcriptional activity of CCAAT/enhancer-binding protein-alpha. Leukemia 2005; 19: 1239-47
132. Leardi A, Caraglia M, Selleri C, et al. Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells. Br J Haematol 1998; 102: 746-52
133. Jensen PD, Jensen IM, Ellegaard J. Desferrioxamine treatment reduces blood transfusion requirements in patients with myelodysplastic syndrome. Br J Haematol 1992; 80: 121-4
134. Marsh JH, Hundert M, Schulman P. Deferoxamine-induced restoration of haematopoiesis in myelofibrosis secondary to myelodysplasia. Br J Haematol 1990; 76: 148-9
135. Meo A, Ruggeri A, La Rosa MA, et al. Iron burden and liver fibrosis decrease during a long-term phlebotomy program and iron chelating treatment after bone marrow transplantation. Hemoglobin 2006; 30: 131-7
136. Cermak J. Erythropoietin administration may potentiate mobilization of storage iron in patients on oral iron chelation therapy. Hemoglobin 2006; 30: 105-12
137. Kersten MJ, Lange R, Smeets ME, et al. Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. Ann Hematol 1996; 73: 247-52
138. al Refaie FN, Wonke B, Hoffbrand AV. Deferiprone-associated myelotoxicity. Eur J Haematol 1994; 53: 298-301
139. Gattermann N, Cazzola M, Greenberg P, et al. The efficacy and tolerability of ICL670, a once-daily oral iron chelator, in patients with myelodysplastic syndromes (MDS) and iron overload. Leuk Res 2005; 29 Suppl. 1: S76
140. Angelucci E, Muretto P, Lucarelli G, et al. Treatment of iron overload in the 'ex-thalassemic': report from the phlebotomy program. Ann N Y Acad Sci 1998; 850: 288-93
141. Barton JC, Lee PL. Disparate phenotypic expression of ALAS2 R452H (nt 1407 G --> A) in two brothers, one with severe sideroblastic anemia and iron overload, hepatic cirrhosis, and hepatocellular carcinoma. Blood Cells Mol Dis 2006; 36: 342-6
142. Caines AE, Kpodonu J, Massad MG, et al. Cardiac transplantation in patients with iron overload cardiomyopathy. J Heart Lung Transplant 2005; 24: 486-8
143. Barton JC, Edwards CQ, Bertoli LF, et al. Iron overload in African Americans. Am J Med 1995; 99: 616-23
144. Hoffbrand AV, Bartlett AN, Veys PA, et al. Agranulocytosis and thrombocytopenia in patient with Blackfan-Diamond anaemia during oral chelator trial [letter]. Lancet 1989; II: 457
145. Alter BP. Agranulocytosis and thrombocytopenia, Blackfan-Diamond anaemia, and oral chelation [letter]. Lancet 1990; 335: 970
146. Kontoghiorghes GJ, Bartlett AN, Sheppard L, et al. Oral iron chelation therapy with deferiprone. Monitoring of biochemical, drug and iron excretion changes. Arzneimittelforschung 1995; 45: 65-9
147. Donovan JM, Plone M, Dagher R, et al. Preclinical and clinical development of deferitrin, a novel, orally available iron chelator. Ann N Y Acad Sci 2005; 1054: 492-4
148. Hider RC, Zhou T. The design of orally active iron chelators. Ann N Y Acad Sci 2005; 1054: 141-54
149. Kontoghiorghes GJ. Future chelation monotherapy and combination therapy strategies in thalassemia and other conditions: comparison of deferiprone, deferoxamine, ICL670, GT56-252, L1NAll and starch deferoxamine polymers. Hemoglobin 2006; 30: 329-47