Decision points in the treatment of transfusional iron overload in patients with myelodysplastic syndromes: why, when, and how to chelate

Abstract

Patients with myelodysplastic syndromes (MDS) differ from those with other transfusion-dependent conditions (eg, thalassemia) as they are typically older, have comorbid conditions, and a generally shorter life expectancy. The underlying disease process in MDS and frequent use of red blood cell transfusions lead to iron accumulation and ultimately organ damage. Whether iron-reducing interventions such as chelation therapy can improve outcomes in this population is currently under investigation. Areas covered: We reviewed published English-language articles from PubMed on the topic of iron overload (IO) in MDS, and the use of iron chelation therapies (ICTs) to alleviate iron burden. Expert commentary: Data on IO-associated complications in MDS are derived largely from retrospective studies and there are limited data to guide clinicians on major treatment decisions. Although effective and well-tolerated oral ICTs are available, and general recommendations may be made regarding usage in MDS, guidance is not yet based on prospective data. The clinical endpoints and assessments for MDS may differ substantively from those used in patients with thalassemia, as an older population may have competing causes for morbidity. We expect that emergent data from clinical trials currently underway will define more appropriate endpoints/assessments for the MDS population in clinical trials.

Iron overload impairs normal hematopoietic stem and progenitor cells through reactive oxygen species and shortens survival in myelodysplastic syndrome mice

“… 1 , 2 Because of chronic anemia, up to 80% of MDS patients become transfusion dependent. 3 Due to repeated blood transfusion and ineffective hematopoiesis, most MDS patients can eventually develop iron overload. Excessive iron can deposit in the liver, heart, spleen, pancreas, bone marrow (BM) and other tissues, resulting in tissue damage and fibrosis, and a series of complications which seriously affect the prognosis of MDS patients.…”

Development of a core outcome set for myelodysplastic syndromes – a Delphi study from the EUMDS Registry Group

“…Reporting bias has frequently been observed in haematological studies and in clinical trials performed on MDS patients, 6,7 and comparison of treatment effectiveness is therefore challenging 8,9 . For the evaluation of evidence‐based treatment effectiveness, the validity of evidence syntheses is an essential factor.…”