Controversies surrounding iron chelation therapy for MDS

The myelodysplastic syndromes (MDS) are characterized by cytopenias and acute myeloid leukemia risk. Most MDS patients eventually require transfusion of red blood cells for anemia, placing them at risk of iron overload (IOL). In beta-thalassemia major, transfusional IOL leads to organ dysfunction and death, however, with iron chelation therapy survival improved to near normal and organ function was improved. In lower risk MDS, several non-randomized studies suggest an adverse effect of IOL on survival, and that lowering iron minimizes this impact and may improve organ function. While guidelines for MDS generally recommend chelation in selected lower risk patients, data are emerging suggesting IOL may impact adversely on the outcome of higher risk MDS and stem cell transplantation (SCT) and that lowering iron may be beneficial in these patients. Trials to determine whether these effects are truly from lowering iron are currently enrolling. Chelation is costly and potentially toxic, and in MDS should be initiated after weighing potential risks and benefits for each patient until more definitive data are available. In this paper, data on the impact of IOL in MDS and SCT, possible mechanisms of iron toxicity such as oxidative stress, and the impact of lowering iron on organ function and survival are reviewed.