Table 1.

Adverse Effects of Deferasirox in the EPIC Study*

Table 2.

Adverse Effects of Deferasirox in the US03 Trial*

Table 3.

Representative Clinical Guidelines Concerning Iron Chelation Therapy for Patients with MDS

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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.
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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.
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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.
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.
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.
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.
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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.
Lesnefsky EJ. Tissue iron overload and mechanisms of iron-catalyzed oxidative injury. Adv Exp Med Biol 1994;366:129–146.
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Author(s)

David P. Steensma, MD

Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachussets

Disclosures

Disclosure: David P. Steensma, MD, has disclosed the following relevant financial relationships:
Served on the advisory board for: Novartis Pharmaceuticals Corporation

Editor(s)

Kerrin M. Green, MA

Assistant Managing Editor, Journal of the National Comprehensive Cancer Network

Disclosures

Disclosure: Kerrin M. Green, MA, has disclosed no relevant financial relationships.

CME Author(s)

Charles P. Vega, MD

Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine

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Disclosure: Charles P. Vega, MD, has disclosed no relevant financial relationships.

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Nafeez Zawahir, MD

CME Clinical Director, Medscape, LLC

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Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

Sarah Fleischman

CME Program Manager, Medscape, LLC

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Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

CME

The Role of Iron Chelation Therapy for Patients With Myelodysplastic Syndromes

Authors: David P. Steensma, MD
CME Released: 1/14/2011
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 1/14/2012, 11:59 PM EST

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Target Audience and Goal Statement

This activity is intended for hematologists and other physicians who care for patients with MDS.

The goal of this activity is to evaluate the balance of benefits vs potential harms of iron chelation therapy among patients with MDS.

Upon completion of this activity, participants will be able to:

Describe the association between MDS and anemia
Evaluate iron overload in patients with MDS
Distinguish benefits of iron chelation therapy among patients with iron overload in MDS
Identify adverse events associated with oral iron chelation therapy

Disclosures

Author(s)

David P. Steensma, MD

Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachussets

Disclosures

Disclosure: David P. Steensma, MD, has disclosed the following relevant financial relationships:
Served on the advisory board for: Novartis Pharmaceuticals Corporation

Editor(s)

Kerrin M. Green, MA

Assistant Managing Editor, Journal of the National Comprehensive Cancer Network

Disclosures

Disclosure: Kerrin M. Green, MA, has disclosed no relevant financial relationships.

CME Author(s)

Charles P. Vega, MD

Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine

Disclosures

Disclosure: Charles P. Vega, MD, has disclosed no relevant financial relationships.

CME Reviewer(s)

Nafeez Zawahir, MD

CME Clinical Director, Medscape, LLC

Disclosures

Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

Sarah Fleischman

CME Program Manager, Medscape, LLC

Disclosures

Disclosure: Sarah Fleischman has disclosed no relevant financial relationships.

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Abstract and Introduction

Abstract

The appropriate role of iron chelation therapy in the management of patients with myelodysplastic syndromes (MDS) is currently controversial. Some investigators interpret data to indicate that careful attention to iron parameters, with early initiation of iron chelation in patients with evidence suggesting transfusion-associated iron overload, is an important component of high-quality MDS patient care. Other physicians are more skeptical, noting that chelation can be cumbersome or costly, has associated risks, and has not yet been shown to reduce morbidity or mortality in the MDS setting. This article reviews the extent to which iron chelation therapy might be either an important clinical intervention in MDS or a distraction from more pressing clinical concerns. (JNCCN 2011;9:65–75)

Introduction

More than 90% of patients with myelodysplastic syndromes (MDS) are anemic at the time of diagnosis,^[1] and most patients will require red blood cell (RBC) transfusions at some point during the course of their illness. Patients with MDS who require RBC transfusions experience worse outcomes than transfusion-independent patients, even when the cohorts are matched for other known disease-associated prognostic markers.^[2,3]

The specific reasons why patients with MDS requiring transfusions experience more rapid disease progression and shorter overall survival are currently unclear. RBC transfusion dependence might mark patients who have intrinsically more severe marrow failure and more dangerous disease, but the RBC transfusions themselves also likely confer risks. Several recent investigations have focused on the specific risk of transfusion-associated iron overload (hemosiderosis) in MDS, because each RBC unit contains approximately 200 to 250 mg of elemental iron, and humans lack a physiologic excretion mechanism for excess iron. Iron overload from increased gut iron absorption in the setting of ineffective erythropoiesis, exacerbated by RBC transfusions, has proven to be a leading cause of death in several congenital forms of anemia, such as severe β-thalassemia.^[4]

The risk of iron overload in chronic acquired anemic states, such as MDS, could be clinically relevant, because this risk is potentially modifiable with iron chelation therapy (ICT). However, which patients with MDS should be offered ICT is currently an area of uncertainty in clinical practice.^[5] Although the advent of an effective orally bioavailable iron chelator, deferasirox (Exjade, approved by the FDA in 2005; deferiprone [L1], another orally administered iron chelator, is available in many countries but not in the United States) promised increased convenience for patients compared with injectable deferoxamine (Desferal, FDA-approved in 1968), ICT is costly and confers risks, and thus far no completed randomized clinical trials have shown that patients with MDS benefit from ICT. This article discusses the evidence supporting the concept that iron overload is harmful to patients with MDS, benefits and risks of ICT, preliminary data from phase II deferasirox clinical trials, and the various consensus guidelines on management of excess iron in patients with MDS.

Page 1 of 7

Evidence of Possible Harm From Iron Overload in MDS

CME Information

Abstract and Introduction
Evidence of Possible Harm From Iron Overload in MDS
Potential Benefits from ICT
Clinical Trial Results and Plans
Risks of ICT
Guidelines
Conclusions

References

References

Disclaimer

The material presented here does not necessarily reflect the views of Medscape, LLC, or companies that support educational programming on www.medscape.org. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.

Table 1.

Table 2.

Table 3.

References

Faculty and Disclosures

Author(s)

David P. Steensma, MD

Editor(s)

Kerrin M. Green, MA

CME Author(s)

Charles P. Vega, MD

CME Reviewer(s)

Nafeez Zawahir, MD

Sarah Fleischman

CME

The Role of Iron Chelation Therapy for Patients With Myelodysplastic Syndromes

Target Audience and Goal Statement

Disclosures

Author(s)

David P. Steensma, MD

Editor(s)

Kerrin M. Green, MA

CME Author(s)

Charles P. Vega, MD

CME Reviewer(s)

Nafeez Zawahir, MD

Sarah Fleischman

Accreditation Statements

For Physicians

Instructions for Participation and Credit

The Role of Iron Chelation Therapy for Patients With Myelodysplastic Syndromes

Abstract and Introduction

Abstract

Introduction

Table of Contents