Iron chelation therapy (ICT) plays a key role in reducing iron overload in patients with transfusion-dependent lower-risk myelodysplastic syndrome (MDS). A recent review article in the Journal of Blood Medicine outlined the role of ICT in patients with MDS based on risk status. The review was authored by Sarah Parisi, MD, PhD, and Carlo Finelli, MD, of IRCCS Azienda Ospedaliero-Universitaria di Bologna in Bologna, Italy.

As the authors explained in their report, iron overload is commonly found in patients with MDS, with chronic blood transfusions being the greatest risk factor for this outcome, although other factors related to iron hemostasis may also contribute. Iron overload is linked to multiple negative impacts, such as reduced overall and leukemia-free survival and evidence of iron toxicity in various organs, such as the liver, the heart, and others.

“The excess of iron not only is responsible for organ damage, but it is able to induce genomic instability and to modify the hematopoietic niche, favoring progression to acute leukemia,” the authors wrote in their review.


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ICT is frequently used for to treat iron overload, with the iron chelators deferoxamine and deferasirox used for patients with MDS. Another chelator, deferiprone, also exists but has limited utility with MDS because of a risk of neutropenia, the authors explained in their review. They described deferasirox as the iron chelator used most commonly with MDS, emphasizing greater efficacy with this agent than with deferoxamine.

Indications for ICT can very according to MDS risk status. According to the authors, international guidelines recommend that patients with low-risk MDS receive ICT in 1 or more of the following circumstances: transfusion dependency with ≥20 red blood cell units transfused, although they noted this threshold is under discussion; serum ferritin levels >1000 ng/dL; and a life expectancy exceeding 12 months. The authors indicated that in patients with lower-risk MDS, ICT has shown evidence of improved event-free survival and potentially overall survival.

The reviewers proposed characteristics to consider that may position patients with intermediate- and high-risk MDS as candidates for ICT. These include good performance status, an age of 65 years or less, adequate liver and kidney function, no significant comorbidities, and a potential to receive disease-modifying treatments, such as hypomethylating agents and/or allogeneic stem cell transplantation. They also recommended that candidates for allogeneic hematopoietic stem cell transplantation receive ICT because of potential impacts of free unbound iron on transplant outcomes.

The authors additionally mentioned improvements in peripheral cytopenias that have been observed with deferasirox therapy. “Further studies are also needed to evaluate and clarify the biological basis of hematological improvement induced by ICT in MDS patients,” they concluded in their review.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Parisi S, Finelli C. Prognostic factors and clinical considerations for iron chelation therapy in myelodysplastic syndrome patients. J Blood Med. 2021;12:1019-1030. doi:10.2147/JBM.S287876