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Published on: October 3, 2018
Iron overload in myelodysplastic syndromes
Sameer Mahesh1, Yelena Ginzburg, Amit Verma
1Albert Einstein College of Medicine, Cancer Center, Bronx, NY, USA.
Abstract:
Myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective hematopoiesis that leads to peripheral cytopenias. Iron overload results from high transfusion requirements and retrospective studies have shown it to be associated with relatively poor survival in a subset of the low risk patients. Recent discoveries have led to the identification of hepcidin as a key regulator of iron metabolism and to the association of non-transferrin bound iron moieties, such as labile plasma iron, with the end organ damage in iron overload states. Currently, there is limited data in evaluating the role of iron chelators in MDS and data from studies in Thalassemia and hemachromostosis have been used to predict ferritin levels above 1000 - 2500 ng/mL and history of 20 blood transfusions as clinical end points for considering iron chelation in MDS. Deferoxamine and deferasirox, the two iron chelators approved for use in the US, have shown efficacy in reducing iron overload in MDS in retrospective studies are now being evaluated for effects on overall survival in prospective studies. On the basis of retrospective data, it is reasonable to offer iron chelation to the lower risk MDS patients requiring frequent transfusions, while monitoring for specific adverse affects in patients on treatment.
Insights
Iron overload in myelodysplastic syndromes (MDS) impacts survival. Iron chelation therapy is recommended for low-risk MDS patients with high transfusion needs, pending further survival data.
Area of Science:
- Hematology
- Iron Metabolism
Background:
- Myelodysplastic syndromes (MDS) cause ineffective blood cell production leading to low blood counts.
- Iron overload, often due to frequent blood transfusions, is linked to poorer survival in some MDS patients.
- Hepcidin's role in iron regulation and labile plasma iron's contribution to organ damage are recent findings.
Purpose of the Study:
- To evaluate the role and efficacy of iron chelators in managing iron overload in MDS patients.
- To determine appropriate clinical endpoints for initiating iron chelation therapy in MDS.
- To assess the impact of iron chelation on overall survival in MDS.
Main Methods:
- Review of retrospective studies on iron overload and chelation in MDS.
- Extrapolation of data from thalassemia and hemochromatosis studies to define chelation criteria (ferritin >1000-2500 ng/mL, >20 transfusions).
- Ongoing prospective studies evaluating deferoxamine and deferasirox for efficacy and survival benefits in MDS.
Main Results:
- Retrospective data suggest iron chelators (deferoxamine, deferasirox) can reduce iron overload in MDS.
- Established criteria for considering iron chelation based on ferritin levels and transfusion history.
- Efficacy of current iron chelators is being further investigated in ongoing trials.
Conclusions:
- Iron chelation is a reasonable consideration for low-risk MDS patients with significant transfusion requirements.
- Close monitoring for adverse effects during iron chelation therapy is essential.
- Further prospective studies are needed to confirm survival benefits of iron chelation in MDS.
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