Iron overload due to regular transfusions of packed red cells can cause multiple organ damage. Iron chelation therapy (ICT) is important in patients with aplastic anemia (AA) who require blood transfusions as supportive management. With the introduction of the oral iron chelator deferasirox, ICT has become more widely available and feasible. We studied 4 adult AA patients who had transfusion-induced iron overload and showed hematological improvement after ICT with oral deferasirox. Following deferasirox treatment, hemoglobin increased and serum ferritin levels decreased, and the patients subsequently became transfusion independent. Our experience raises the possibility of the potential benefit of ICT on hematopoiesis. Further long-term studies in larger patient cohorts are needed to clarify the effect of the restoration of hematopoiesis after iron chelation therapy.

Keywords:
Transfusion dependence, Aplastic anemia, Deferasirox, Hematopoiesis, Iron chelation therapy
1.
Zurlo MG, De Stefano P, Borgna-Pignatti C, Di Palma A, Piga A, Melevendi C, Di Gregorio F, Burattini MG, Terzoli S: Survival and causes of death in thalassaemia major. Lancet 1989;2:27–30.
2.
Takatoku M, Uchiyama T, Okamoto S, Kanakura Y, Sawada K, Tomonaga M, Nakao S, Nakahata T, Harada M, Murate T, Ozawa K: Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality. Eur J Haematol 2007;78:487–494.
3.
Schafer AI, Cheron RG, Dluhy R, Cooper B, Gleason RE, Soeldner JS, Bunn HF: Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med 1981;304:319–324.
4.
Cappellini MD, Taher A: Long-term experience with deferasirox (ICL670), a once-daily oral iron chelator, in the treatment of transfusional iron overload. Expert Opin Pharmacother 2008;9:2391–2402.
5.
Koh KN, Park M, Kim BE, Im HJ, Seo JJ: Restoration of hematopoiesis after iron chelation therapy with deferasirox in 2 children with severe aplastic anemia. J Pediatr Hematol Oncol 2010;32:611–614.
6.
Lee JW, Jang PS, Chung NG, Cho B, Jeong DC, Kim HK: Iron chelation therapy with deferasirox results in recovery of hematopoiesis in a child with aplastic anemia. Pediatr Hematol Oncol 2011;28:718–720.
7.
Park SJ, Han CW: Complete hematopoietic recovery after continuous iron chelation therapy in a patient with severe aplastic anemia with secondary hemochromatosis. J Korean Med Sci 2008;23:320–323.
8.
Delea TE, Hagiwara M, Phatak PD: Retrospective study of the association between transfusion frequency and potential complications of iron overload in patients with myelodysplastic syndrome and other acquired hematopoietic disorders. Curr Med Res Opin 2009;25:139–147.
9.
Lee JW: Iron chelation therapy in the myelodysplastic syndromes and aplastic anemia: a review of experience in South Korea. Int J Hematol 2008;88:16–23.
10.
Wimazal F, Nosslinger T, Baumgartner C, Sperr WR, Pfeilstocker M, Valent P: Deferasirox induces regression of iron overload in patients with myelodysplastic syndromes. Eur J Clin Invest 2009;39:406–411.
11.
Wood JC, Kang BP, Thompson A, Giardina P, Harmatz P, Glynos T, Paley C, Coates TD: The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. Blood 2010;116:537–543.
12.
Lee JW, Yoon SS, Shen ZX, Ganser A, Hsu HC, Habr D, Domokos G, Roubert B, Porter JB: Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial. Blood 2010;116:2448–2454.
13.
Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, Harris JW: Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 1994;331:567–573.
14.
Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, Martin M, Koren G, Cohen AR: Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994;331:574–578.
15.
Rose C, Brechignac S, Vassilief D, Pascal L, Stamatoullas A, Guerci A, Larbaa D, Dreyfus F, Beyne-Rauzy O, Chaury MP, Roy L, Cheze S, Morel P, Fenaux P: Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM (Groupe Francophone des Myelodysplasies). Leuk Res 2010;34:864–870.
16.
Guariglia R, Martorelli MC, Villani O, Pietrantuono G, Mansueto G, D’Auria F, Grieco V, Bianchino G, Lerose R, Bochicchio GB, Musto P: Positive effects on hematopoiesis in patients with myelodysplastic syndrome receiving deferasirox as oral iron chelation therapy: a brief review. Leuk Res 2011;35:566–570.
17.
Messa E, Cilloni D, Messa F, Arruga F, Roetto A, Saglio G: Deferasirox treatment improved the hemoglobin level and decreased transfusion requirements in four patients with the myelodysplastic syndrome and primary myelofibrosis. Acta Haematol 2008;120:70–74.
18.
Capalbo S, Spinosa G, Franzese MG, Palumbo G: Early deferasirox treatment in a patient with myelodysplastic syndrome results in a long-term reduction in transfusion requirements. Acta Haematol 2009;121:19–20.
19.
Oliva EN, Ronco F, Marino A, Alati C, Pratico G, Nobile F: Iron chelation therapy associated with improvement of hematopoiesis in transfusion-dependent patients. Transfusion 2010;50:1568–1570.
20.
Nishiuchi T, Okutani Y, Fujita T, Yoshida K, Ohnishi H, Haba R: Effect of iron chelator deferasirox on chronic anemia and thrombocytopenia in a transfusion-dependent patient with myelodysplastic syndrome. Int J Hematol 2010;91:333–335.
21.
Breccia M, Loglisci G, Salaroli A, Cannella L, Santopietro M, Alimena G: Deferasirox treatment interruption in a transfusion-requiring myelodysplastic patient led to loss of erythroid response. Acta Haematol 2010;124:46–48.
22.
Jensen PD, Heickendorff L, Pedersen B, Bendix-Hansen K, Jensen FT, Christensen T, Boesen AM, Ellegaard J: The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. Br J Haematol 1996;94:288–299.
23.
Vreugdenhil G, Smeets M, Feelders RA, van Eijk HG: Iron chelators may enhance erythropoiesis by increasing iron delivery to haematopoietic tissue and erythropoietin response in iron-loading anaemia. Acta Haematol 1993;89:57–60.
24.
Kontoghiorghes GJ, May A: Uptake and intracellular distribution of iron from transferrin and chelators in erythroid cells. Biol Met 1990;3:183–187.
25.
Louache F, Testa U, Pelicci P, Thomopoulos P, Titeux M, Rochant H: Regulation of transferrin receptors in human hematopoietic cell lines. J Biol Chem 1984;259:11576–11582.
26.
Wang GL, Semenza GL: Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood 1993;82:3610–3615.
27.
Taoka K, Kumano K, Nakamura F, Hosoi M, Goyama S, Imai Y, Hangaishi A, Kurokawa M: The effect of iron overload and chelation on erythroid differentiation. Int J Hematol 2012;95:149–159.
© 2012 S. Karger AG, Basel
2012
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