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Pathogenesis and Management of Iron Overload in MDS

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The Myelodysplastic Syndromes

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Abstract

Iron overload in MDS is the joint outcome of multiple blood transfusions and inappropriately increased iron absorption associated with ineffective erythropoiesis. Experience gained in hereditary iron-loading anemias indicates that the long-term consequences of iron toxicity are preventable and reversible by effective iron chelation therapy (ICT). With the introduction of orally effective iron chelators that are easy to take and suitable for use in elderly patients, there is increasing interest in offering ICT to patients with MDS. Ideally, evidence supporting the beneficial effects of iron chelation in MDS should rest on proof of improved life expectancy and in exceptional cases, reversal of myocardial disease. However, such evidence is presently unavailable.

The selection of MDS patients who may benefit from ICT involves a number of considerations: Life-limiting transfusional iron overload is only relevant for MDS patients with a relatively favourable prognosis. All currently available studies on transfusion-related myocardial toxicity indicate that significant cardiac siderosis may only be expected after the cumulative transfusion of over 100 units of blood, requiring several years of intensive transfusion therapy. Serum ferritin in MDS is a poor indicator of iron overload and recommendations for ICT based on threshold ferritin values should be replaced by state-of-the-art MRI methodology.

Retrospective uncontrolled studies in MDS suggest a protective effect of ICT against iron-related mortality, decreased transfusion requirements and possibly decreased rates of leukemic transformation. However, additional well designed studies are needed to document the beneficial effects of long term ICT in order to justify the cost, potential toxicity, and other public health implications of such treatment in transfusion dependent MDS patients.

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Acknowledgment

The author was the recipient of travel support and honoraria from Novartis Basel Switzerland and Apotex Toronto Canada.

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  1. Department of Hematology, Shaare Zedek Medical Center, PO Box 3235, Jerusalem, Israel

    Chaim Hershko

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Correspondence to Chaim Hershko .

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  1. , 3rd Department of Internal Medicine, Semmelweis University, Kútvölgyi út 4, Budapest, 1125, Hungary

    Judit Várkonyi

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Hershko, C. (2011). Pathogenesis and Management of Iron Overload in MDS. In: Várkonyi, J. (eds) The Myelodysplastic Syndromes. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0440-4_12

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