How I treat iron overload in adult myelodysplastic syndrome

While clinical benefits of iron chelation therapy (ICT) in red blood cell transfusion dependent (RBC TD) hereditary anemias such as beta-thalassemia major are incontrovertible, the evidence supporting a similar benefit in patients with TD myelodysplastic neoplasms (MDS) and iron overload (IOL) is sometimes debated. MDS presents later in life, has a limited repertoire of life extending therapies, and patients may have comorbidities acting as competing causes of death. However, refined prognostication identifies MDS patients with a reasonable life expectancy, and since 50% of patients will ultimately become RBC transfusion dependent and develop transfusional iron overload (IOL), iron chelation therapy (ICT) should be considered in some. Using illustrative cases, we summarize mechanisms of iron toxicity, strategies for the identification of IOL and propose definitions of IOL severity. We provide rationale for and recommend which patients may benefit from ICT. We discuss currently available chelators, their administration, monitoring, side effects and their management. Given challenges with the use of iron chelators, we suggest the nuances to be considered when planning chelation initiation include the rate of iron accumulation, the presence of organ iron and/or dysfunction, and detectable indicators of oxidative stress. Areas for future investigation are identified.