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Research Article Open access CC BY 3.0

Iron Overload, Chelation Therapy and Survival in Lower-Risk Myelodysplastic Syndromes: State of the Evidence

Roger M. Lyons

International Blood Research & Reviews · pp. 95–112 · Published 22 Feb 2014

10.9734/IBRR/2014/8580

Abstract

Myelodysplastic syndromes (MDS) are clonal stem cell disorders that primarily affect older persons and are associated with peripheral blood cytopenias, increased risk of conversion to acute myeloid leukemia and shortened survival. Treatment strategies in MDS are guided by patient risk categories, with higher-risk patients receiving more aggressive interventions. Patients with lower-risk MDS receive less aggressive therapies or supportive care/red blood cell transfusion. Transfusion-dependent patients with lower-risk MDS are likely to develop iron overload because of their longer predicted survival and, hence, greater transfusion burden. Transfusion requirement and elevated serum ferritin further complicate the treatment landscape because they have dose-dependent effects on overall and leukemia-free survival, with increasing serum ferritin levels associated with increased risk of death. Lower iron burden could provide a survival benefit, and an association with improved survival has been shown in retrospective studies. However, lack of random assignment to treatment is the major flaw in these studies, which potentially introduces patient selection bias. Despite the lack of randomization and other issues with trial design, available studies have shown consistent results, which suggest a survival benefit in transfusion-dependent patients with MDS who have received chelation therapy. Prospective studies are needed to confirm this observation. The possible mechanisms by which chelation therapy appears to benefit patients with MDS need further research. The data suggesting a survival benefit from chelation therapy in lower-risk, iron-overloaded patients with MDS are reviewed, including the strength of evidence, recent scientific advances and ongoing clinical trials.  

Myelodysplastic syndromes iron overload chelation survival leukemia

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