Managing iron overload in patients with myelodysplastic syndromes with oral deferasirox therapy

Oncologist

Volumn 14, Issue 5, 2009, Pages 489-496

  Jabbour, Elias ^a   Garcia Manero, Guillermo ^a   Taher, Ali ^b   Kantarjian, Hagop M ^a  

^a UNIVERSITY OF TEXAS   (United States)

^b AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

Author keywords

Deferasirox; Iron overload; Myelodysplastic syndromes; Oral iron chelator; Red blood cell transfusions

Indexed keywords

DEFERASIROX; DEFEROXAMINE; FERRITIN; IRON;

ACUTE KIDNEY FAILURE; AMINOTRANSFERASE BLOOD LEVEL; BETA THALASSEMIA; CHELATION THERAPY; CLINICAL EVALUATION; CLINICAL TRIAL; CONTINUOUS INFUSION; CREATININE BLOOD LEVEL; DIARRHEA; DOSE RESPONSE; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENDOCRINE DISEASE; ERYTHROCYTE TRANSFUSION; FERRITIN BLOOD LEVEL; HEART INJURY; HUMAN; IRON BLOOD LEVEL; IRON CHELATION; IRON INTAKE; IRON OVERLOAD; LIVER INJURY; MYELODYSPLASTIC SYNDROME; NEUTROPENIA; OPTIMAL DRUG DOSE; OVERALL SURVIVAL; PATIENT COUNSELING; PATIENT EDUCATION; PATIENT MONITORING; PRIORITY JOURNAL; RASH; RECOMMENDED DRUG DOSE; REVIEW; SIDE EFFECT; SURVIVAL TIME; THROMBOCYTOPENIA;

ADMINISTRATION, ORAL; BENZOIC ACIDS; ERYTHROCYTE TRANSFUSION; FERRITINS; HUMANS; IRON; IRON CHELATING AGENTS; IRON OVERLOAD; MYELODYSPLASTIC SYNDROMES; TRIAZOLES;

EID: 66349122711     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2008-0154     Document Type: Review

References (53)

1. Aul C, Bowen DT, Yoshida Y. Pathogenesis, etiology and epidemiology of myelodysplastic syndromes. Haematologica 1998;83:71-86. (Pubitemid 28096504)
2. Estey E. Acute myeloid leukemia and myelodysplastic syndromes in older patients. J Clin Oncol 2007;25:1908-1915. (Pubitemid 46854425)
3. Leukemia Research Fund. Myelodysplastic Syndromes: Information and education. Available at http://www.irf.org.uk/en/1/dismdshome.html, accessed February 3, 2009.
4. Andrews NC. Disorders of iron metabolism. N Engl J Med 1999;341:1986-1995. (Pubitemid 30010408)
5. Gattermann N, Porter J, Lopes LF et al. Consensus statement on iron overload in myelodysplastic syndromes. Hematol Oncol Clin North Am 2005;19(suppl 1):18-25.
6. Cortelezzi A, Cattaneo C, Cristiani S et al. Non-transferrin-bound iron in myelodysplastic syndromes: A marker of ineffective erythropoiesis? Hematol J 2000;1:153-158.
7. Malcovati L, Della 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;23:7594-7603. (Pubitemid 46291823)
8. Leitch HA. Improving clinical outcome in patients with myelodysplastic syndrome and iron overload using iron chelation therapy. Leuk Res 2007;31(suppl 3):S7-S9. (Pubitemid 350137501)
9. Zurlo MG, De Stefano P, Borgna-Pignatti C et al. Survival and causes of death in thalassaemia major. Lancet 1989;2:27-30. (Pubitemid 19158169)
10. Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann N Y Acad Sci 1998;850:191-201. (Pubitemid 28369759)
11. Brittenham GM, Griffith PM, NienhuisAWet al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 1994;331:567-573. (Pubitemid 24265698)
12. Shalitin S, Carmi D, Weintrob N et al. Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients. Eur J Haematol 2005;74:93-100. (Pubitemid 40175311)
13. Thakerngpol K, Fucharoen S, Boonyaphipat P et al. Liver injury due to iron overload in thalassemia: Histopathologic and ultrastructural studies. Biometals 1996;9:177-183. (Pubitemid 26144598)
14. Vichinsky E, Butensky E, Fung E et al. Comparison of organ dysfunction in transfused patients with SCD or β thalassemia. Am J Hematol 2005;80:70-74. (Pubitemid 41254272)
15. Telfer PT, Prestcott E, Holden S et al. Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. Br J Haematol 2000;110:971-977.
16. Leitch HA, Goodman TA, Wong KK et al. Improved survival in patients with myelodysplastic syndrome (MDS) receiving iron chelation therapy. Blood 2006;108:78a.
17. Brittenham GM, Badman DG. Noninvasive measurement of iron: Report of an NIDDK workshop. Blood 2003;101:15-19. (Pubitemid 36025881)
18. Cohen AR, Galanello R, Pennell DJ et al. Thalassemia. Hematology Am Soc Hematol Educ Program 2004:14-34.
19. Modell B, Khan M, Darlison M. Survival in β-thalassaemia major in the UK: Data from the UK Thalassaemia Register. Lancet 2000;355:2051-2052. (Pubitemid 30339248)
20. Ehlers KH, Levin AR, Markenson AL et al. Longitudinal study of cardiac function in thalassemia major. Ann N Y Acad Sci 1980;344:397-404.
21. Jaeger M, Aul C, Sohngen D et al. [Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes]. Beitr Infusionsther 1992;30:464-468. In German.
22. Buja LM, Roberts WC. Iron in the heart. Etiology and clinical significance. Am J Med 1971;51:209-221.
23. Jensen PD, Jensen FT, Christensen T et al. Evaluation of myocardial iron by magnetic resonance imaging during iron chelation therapy with deferrioxamine: Indication of close relation between myocardial iron content and chelatable iron pool. Blood 2003;101:4632-4639. (Pubitemid 36857840)
24. Goldberg SL, Mody-Patel N, Chen ER. Clinical and economic consequences of myelodysplastic syndromes in the United States: An analysis of the Medicare database. Blood 2008;112:237.
25. Sanz G, Nomdedeu B, Such E et al. Independent impact of iron overload and transfusion dependency on survival and leukemic evolution in patients with myelodysplastic syndrome. Blood 2008;112:238.
26. Cazzola M, Malcovati L. Myelodysplastic syndromes - coping with ineffective hematopoiesis. N Engl J Med 2005;352:536-538. (Pubitemid 40204666)
27. Takatoku M, Uchiyama T, Okamoto S et al. 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. (Pubitemid 46753591)
28. Gabutti V, Piga A. Results of long-term iron-chelating therapy. Acta Haematol 1996;95:26-36. (Pubitemid 26071428)
29. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood 1997;89:739-761. (Pubitemid 27121266)
30. Leitch HA. Improved survival in myelodysplastic syndromes patients receiving iron chelation therapy. Leuk Res 2007;31(suppl 1):S15.
31. Leitch HA, Wong DH, Leger CS et al. Improved leukemia-free and overall survival in patients with myelodysplastic syndrome receiving iron chelation therapy: A subgroup analysis. Blood 2007;110:439a.
32. Rose C, Brechignac S, Vassilief D et al. Positive impact of iron chelation therapy (CT) on survival in regularly transfused MDS patients. A prospective analysis by the GFM. Blood 2007;110:80a.
33. 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;94:288-299. (Pubitemid 26247987)
34. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Myelodysplastic Syndromes. V.1.2009. Available at http://www.nccn.org/professionals/physician-gls/pdf/mds.pdf, accessed February 3, 2009.
35. Jensen PD, Jensen FT, Christensen T et al. Relationship between hepatocellular injury and transfusional iron overload prior to and during iron chelation with desferrioxamine: A study in adult patients with acquired anemias. Blood 2003;101:91-96. (Pubitemid 36025892)
36. Kattamis C, Meddeb B, Ressayre-Djaffer C et al. Baseline iron studies demonstrate severe iron overload in patients enrolled into the deferasirox (Exjade®, ICL670) clinical trial programme. Haematologica 2006;91(suppl 1):415.
37. Porter J, Galanello R, Saglio G et al. Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): A 1-yr prospective study. Eur J Haematol 2008;80:168-176.
38. Gattermann N, Schmid M, Vassilieff D et al. Severe iron overload in patients with myelodysplastic syndromes (MDS) enrolled in a large study of deferasirox (Exjade®, ICL670). Leuk Res 2007;31(suppl 1):S109-S110.
39. List AF, Baer MR, Steensma D et al. Iron chelation with deferasirox (Exjade®) improves iron burden in patients with myelodysplastic syndromes (MDS). Blood 2008;112:236.
40. Baer R, Esposito J, Kang B et al. Iron overload in patients with MDS: Baseline data from studies of the once-daily oral iron chelator, deferasirox (Exjade). Haematologica 2007;92(suppl 1):379.
41. Cabantchik ZI, Breuer W, Zanninelli G et al. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol 2005;18:277-287. (Pubitemid 40298370)
42. Olivieri NF, Nathan DG, MacMillan JH et al. Survival in medically treated patients with homozygous β-thalassemia. N Engl J Med 1994;331:574-578. (Pubitemid 24265699)
43. Cappellini MD, Cohen A, Piga A et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood 2006;107:3455-3462.
44. Galanello R, Piga A, Forni GL et al. Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent, in pediatric patients with β-thalassemia major. Haematologica 2006;91:1343-1351. (Pubitemid 44569807)
45. 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. (Pubitemid 36578996)
46. 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;91:873-880. (Pubitemid 44023139)
47. Vichinsky E, Onyekwere O, Porter J et al. A randomized comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol 2007;136:501-508. (Pubitemid 46046309)
48. Gattermann N, Schmid M, Della Porta M et al. Efficacy and safety of deferasirox (Exjade®) during 1 year of treatment in transfusion-dependent patients with myelodysplastic syndromes: Results from EPIC trial. Blood 2008;112:235.
49. Cappellini MD, Vichinsky E, Galanello R et al. Long-term treatment with deferasirox (Exjade®, ICL670), a once-daily oral iron chelator, is effective in patients with transfusion-dependent anemias. Blood 2007;110:816a.
50. Exjade® (deferasirox) [prescribing information]. Novartis Pharmaceuticals Corporation, 2007. Available at http://www.pharma.us.novartis. com/product/pi/pdf/exjade.pdf, accessed February 3, 2009.
51. List AF, Baer MR, Steensma D et al. Deferasirox (ICL670; Exjade®) reduces serum ferritin (SF) and labile plasma iron (LPI) in patients with myelodysplastic syndromes (MDS). Blood 2007;110:440a.
52. Jensen PD. Evaluation of iron overload. Br J Haematol 2004;124:697-711. (Pubitemid 38365774)
53. Piga A, Aydinok Y, Gathmann I et al. Transfusional requirements are a key factor in tailoring the optimal dose of chelation therapy, as demonstrated by the novel, oral iron chelator deferasirox (Exjade, ICL670). Haematologica 2006;91(suppl 1):388.