The role of iron chelation therapy for patients with myelodysplastic syndromes

JNCCN Journal of the National Comprehensive Cancer Network

Volumn 9, Issue 1, 2011, Pages 65-75

  Steensma, David P ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Deferasirox; Iron chelation therapy; Iron overload; MDS; Myelodysplastic syndromes; Transfusional hemosiderosis

Indexed keywords

DEFERASIROX; DEFERIPRONE; DEFEROXAMINE; FERRITIN; IRON CHELATE; REACTIVE OXYGEN METABOLITE;

ABDOMINAL PAIN; ALLOGENEIC STEM CELL TRANSPLANTATION; ANOREXIA; ARTHRALGIA; BACKACHE; COMORBIDITY; CONSTIPATION; CREATININE BLOOD LEVEL; DIARRHEA; DRUG FATALITY; DYSPNEA; FATIGUE; FERRITIN BLOOD LEVEL; FEVER; HUMAN; INFECTION; IRON BLOOD LEVEL; IRON CHELATION; IRON OVERLOAD; KIDNEY FAILURE; LIVER VEIN OBSTRUCTION; MORBIDITY; MORTALITY; MULTICENTER STUDY (TOPIC); MYELODYSPLASTIC SYNDROME; NAUSEA AND VOMITING; NEUTROPENIA; PATIENT CARE; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL (TOPIC); PNEUMONIA; RASH; REVIEW; SIDE EFFECT; THROMBOCYTOPENIA; TREATMENT OUTCOME; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION;

EID: 78951487148     PISSN: 15401405     EISSN: 15401413     Source Type: Journal    
DOI: 10.6004/jnccn.2011.0007     Document Type: Review

References (55)

1. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:2079-2088.
2. Malcovati L. Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes. Leuk Res 2007;31(Suppl 3):S2-6.
3. Cazzola M, Malcovati L. Myelodysplastic syndromes - coping with ineffective hematopoiesis. N Engl J Med 2005;352:536-538. (Pubitemid 40204666)
4. Olivieri NF, Nathan DG, MacMillan JH, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994;331:574-578.
5. Steensma DP. Myelodysplasia paranoia: iron as the new radon. Leuk Res 2009;33:1158-1163.
6. 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;23:7594-7603.
7. 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.
8. Remacha AF, Arrizabalaga B, Del Canizo C, et al. Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements. Ann Hematol 2010;89:147-154.
9. Wimazal F, Nosslinger T, Baumgartner C, et al. Deferasirox induces regression of iron overload in patients with myelodysplastic syndromes. Eur J Clin Invest 2009;39:406-411.
10. Goldberg SL, Chen E, Corral M, et al. Incidence and clinical complications of myelodysplastic syndromes among United States medicare beneficiaries. J Clin Oncol 2010;28:2847-2852.
11. 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.
12. Armand P, Kim HT, Cutler CS, et al. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood 2007;109:4586-4588.
13. Mahindra A, Bolwell B, Sobecks R, et al. Elevated pretransplant ferritin is associated with a lower incidence of chronic graft-versus-host disease and inferior survival after myeloablative allogeneic haematopoietic stem cell transplantation. Br J Haematol 2009;146:310-316.
14. Pullarkat V, Blanchard S, Tegtmeier B, et al. Iron overload adversely affects outcome of allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2008;42:799-805.
15. Platzbecker U, Bornhauser M, Germing U, et al. Red blood cell transfusion dependence and outcome after allogeneic peripheral blood stem cell transplantation in patients with de novo myelodysplastic syndrome (MDS). Biol Blood Marrow Transplant 2008;14:1217-1225.
16. Park IH, Kim Y, Kim JS, et al. Transfusion-associated iron overload as a predictive factor for poor stem cell mobilization in patients with haematological malignancies. Transfus Med 2008;18:97-103.
17. Chee CE, Steensma DP, Wu W, et al. Neither serum ferritin nor the number of red blood cell transfusions affect overall survival in refractory anemia with ringed sideroblasts. Am J Hematol 2008;83:611-613.
18. Patnaik MM, Lasho TL, Finke CM, et al. WHO-defined 'myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations. Leukemia 2010;24:1283-1289.
19. Chacko J, Pennell DJ, Tanner MA, et al. Myocardial iron loading by magnetic resonance imaging T2* in good prognostic myelodysplastic syndrome patients on long-term blood transfusions. Br J Haematol 2007;138:587-593.
20. Konen E, Ghoti H, Goitein O, et al. No evidence for myocardial iron overload in multitransfused patients with myelodysplastic syndrome using cardiac magnetic resonance T2 technique. Am J Hematol 2007;82:1013-1016.
21. Di Tucci AA, Matta G, Deplano S, et al. Myocardial iron overload assessment by T2* magnetic resonance imaging in adult transfusion dependent patients with acquired anemias. Haematologica 2008;93:1385-1388.
22. Valent P, Sperr WR, Fodinger M, Kundi M. Comorbidity, iron overload and HFE variants: a new prognostic complex in MDS? Eur J Clin Invest 2009;39:1112-1113.
23. DeLoughery TG. Iron: the fifth horseman of the apocalypse? Am J Hematol 2009;84:263-264.
24. Pullarkat V. Objectives of iron chelation therapy in myelodysplastic syndromes: more than meets the eye? Blood 2009;114:5251-5255.
25. List A, Baer M, Steensma D, et al. Deferasirox (ICL670; Exjade) reduces serum ferritin (SF) and labile plasma iron (LPI) in patients with myelodysplastic syndromes (MDS) [abstract]. Blood 2007;110:Abstract 1470.
26. Lesnefsky EJ. Tissue iron overload and mechanisms of iron-catalyzed oxidative injury. Adv Exp Med Biol 1994;366:129-146.
27. 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 [abstract]. Blood 2008;112:Abstract 640.
28. von Bonsdorff L, Sahlstedt L, Ebeling F, et al. Apotransferrin administration prevents growth of Staphylococcus epidermidis in serum of stem cell transplant patients by binding of free iron. FEMS Immunol Med Microbiol 2003;37:45-51.
29. Ghoti H, Fibach E, Merkel D, et al. Changes in parameters of oxidative stress and free iron biomarkers during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndromes. Haematologica 2010;95:1433-1434.
30. Ghoti H, Amer J, Winder A, et al. Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome. Eur J Haematol 2007;79:463-467.
31. Messa E, Carturan S, Maffe C, et al. Deferasirox is a powerful NF-kappaB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from intracellular iron chelation and reactive oxygen species scavenging. Haematologica 2010;95:1308-1316.
32. Badawi MA, Vickars LM, Chase JM, Leitch HA. Red blood cell transfusion independence following the initiation of iron chelation therapy in myelodysplastic syndrome. Adv Hematol 2010;2010:164045.
33. Rose C, Brechignac S, Vassilief D, et al. 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.
34. Leitch HA, Wong DHC, Leger CS, et al. Improved leukemia-free and overall survival in patients with myelodysplastic syndrome receiving iron chelation therapy: a subgroup analysis [abstract]. Blood 2007;110:Abstract1469.
35. 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.
36. Metzgeroth G, Dinter D, Schultheis B, et al. Deferasirox in MDS patients with transfusion-caused iron overload - a phase-II study. Ann Hematol 2009;88:301-310.
37. Greenberg PL, Koller CA, Cabantchik ZI, et al. Prospective assessment of effects on iron-overload parameters of deferasirox therapy in patients with myelodysplastic syndromes. Leuk Res 2010;34:1560-1565.
38. List AF, Baer MR, Steensma D, et al. Iron chelation with deferasirox (Exjade) improves iron burden in patients with myelodysplastic syndromes (MDS) [abstract]. Blood 2008;112:Abstract 634.
39. Gattermann N, Finelli C, Porta MD, et al. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: results from the large 1-year EPIC study. Leuk Res 2010;34:1143-1150.
40. Kontoghiorghes GJ, Eracleous E, Economides C, Kolnagou A. Advances in iron overload therapies. prospects for effective use of deferiprone (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NAll and their combinations. Curr Med Chem 2005;12:2663-2681.
41. List AF, Baer MR, Steensma DP, et al. Two-year analysis of efficacy and safety of deferasirox (Exjade) treatment in myelodysplastic syndrome patients enrolled in the US03 study [abstract]. Blood 2009;114:Abstract 3829.
42. Kontoghiorghes GJ. Introduction of higher doses of deferasirox: better efficacy but not effective iron removal from the heart and increased risks of serious toxicities. Expert Opin Drug Saf 2010;9:633-641.
43. Ibrahim AS, Spellberg B, Edwards J Jr. Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment. Curr Opin Infect Dis 2008;21:620-625.
44. Gattermann N. Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload. Int J Hematol 2008;88:24-29.
45. Schmid M. Iron chelation therapy in MDS: what have we learnt recently? Blood Rev 2009;23(Suppl 1):S21-25.
46. Alessandrino EP, Amadori S, Barosi G, et al. Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology. Haematologica 2002;87:1286-1306.
47. Bowen D, Culligan D, Jowitt S, et al. Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol 2003;120:187-200.
48. Gattermann N PJ, Lopes LF, Seymour J. Consensus statement on iron overload in myelodysplastic syndromes. Hematol Oncol Clin North Am 2005;19(Suppl 1):18-25.
49. Suzuki T, Tomonaga M, Miyazaki Y, et al. Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes. Int J Hematol 2008;88:30-35.
50. Valent P, Krieger O, Stauder R, et al. Iron overload in myelodysplastic syndromes (MDS) - diagnosis, management, and response criteria: a proposal of the Austrian MDS platform. Eur J Clin Invest 2008;38:143-149.
51. Bennett JM. Consensus statement on iron overload in myelodysplastic syndromes. Am J Hematol 2008;83:858-861.
52. Arrizabalaga B, del Cañizo C, Remacha A, et al. [Clinical guide for chelation of patients with myelodysplastic syndrome.] Haematologica 2008;93(Suppl 1):3-10 [in Spanish].
53. Mittelman M, Lugassy G, Merkel D, et al. Iron chelation therapy in patients with myelodysplastic syndromes: consensus conference guidelines. Isr Med Assoc J 2008;10:374-376. (Pubitemid 351902940)
54. Wells RA, Leber B, Buckstein R, et al. Iron overload in myelodysplastic syndromes: a Canadian consensus guideline. Leuk Res 2008;32:1338-1353.
55. Greenberg PL, Attar E, Bennett JM, et al. NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes. Version 2, 2010. Available at: http://www.nccn.org/professionals/physician-gls/PDF/mds.pdf. Accessed November 4, 2010.