Iron chelation therapy in low risk myelodysplastic syndrome

Abstract

Anaemia is the commonest cytopenia seen in patients with myelodysplastic syndrome (MDS), and the majority of patients will require transfusion support at some point. Blood transfusions are rich in iron, which leads to the accumulation of body iron over time. It is accepted that this ultimately causes end organ damage and may impact on both morbidity and mortality. In addition, recent data has increased our interest in the subject with regard to the potential impact on stem cell transplant outcome and an anti-leukaemic effect of iron chelation therapy. There is still debate over which patients should receive iron chelation therapy, but the emergence of new diagnostic and prognostic markers in MDS may help decision making in the clinic setting.

Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases

“…Apparently, the anemia in these patients may be due not only to defects in erythropoiesis but may be also due to an insufficient response to endogenous erythropoietin . Consequently, these patients require blood transfusions and often develop iron overload, a common side effect of transfusions . An oversupply of free iron gives rise to production of ROS by the Haber–Weiss reaction inducing tissue and cell damage (Fig.…”

Therapeutic applications of chelating drugs in iron metabolic disorders of the brain and retina

“…Iron chelation therapy is a well‐established approach for treatment of iron loading in patients with thalassemia, sickle cell disease, and myelodysplasia who require chronic blood transfusions (Brittenham, 2011; Killick, 2017). Given an increased understanding of iron accumulation and ferroptosis in neurodegenerative disease, iron chelators may have therapeutic potential beyond their current application in those requiring chronic blood transfusions.…”

Iron chelators or therapeutic modulators of iron overload: Are we anywhere near ideal one?

“…There seems to be an increasing interest for different iron chelators and labile iron pool for patients with thalassaemia syndromes (thalassaemia major and thalassaemia intermedia) and transfusion-dependent MDS with respect to their efficacy, tolerability, safety, cost and long-term side effects. Several studies have been published recently on this topic123456789. Di Maggio and Maggio4 evaluated 10 trials on various iron chelators singly or in combination for iron overloaded transfusion-dependent beta-thalassaemia major.…”

“…Deferiprone as an iron chelator still does not have wide acceptance in the developed countries outside restricted indications in MDS and myocardial iron overload in combination with deferoxamine6. Iron deposition in multitransfused beta-thalassaemia patients produces clinical effects in mainly three organ systems, i.e .…”

“…The other two i.e . deferasirox and deferiprone have side effects such as agranulocytosis, hepatitis, renal disturbances, gastric intolerance, retinal and auditory toxicity and olfactory disturbances and these may not produce desired level of tissue iron in iron-overloaded state despite adequately intense therapy in some patients underscoring the need for more effective and safe iron chelators for clinical use4610.…”