Controversies on the Consequences of Iron Overload and Chelation in MDS

Abstract. Many patients with MDS are prone to develop systemic and tissue iron overload in part as a consequence of disease-immanent ineffective erythropoiesis. However, chronic red blood cell transfusions, which are part of the supportive care regimen to correct anemia, are the major source of iron...

Full description

Bibliographic Details
Main Authors: Francesca Vinchi, Saskia Hell, Uwe Platzbecker
Format: Article
Language:English
Published: Wiley 2020-06-01
Series:HemaSphere
Online Access:http://journals.lww.com/10.1097/HS9.0000000000000357
_version_ 1797281137466277888
author Francesca Vinchi
Saskia Hell
Uwe Platzbecker
author_facet Francesca Vinchi
Saskia Hell
Uwe Platzbecker
author_sort Francesca Vinchi
collection DOAJ
description Abstract. Many patients with MDS are prone to develop systemic and tissue iron overload in part as a consequence of disease-immanent ineffective erythropoiesis. However, chronic red blood cell transfusions, which are part of the supportive care regimen to correct anemia, are the major source of iron overload in MDS. Increased systemic iron levels eventually lead to the saturation of the physiological systemic iron carrier transferrin and the occurrence of non-transferrin-bound iron (NTBI) together with its reactive fraction, the labile plasma iron (LPI). NTBI/LPI-mediated toxicity and tissue iron overload may exert multiple detrimental effects that contribute to the pathogenesis, complications and eventually evolution of MDS. Until recently, the evidence supporting the use of iron chelation in MDS was based on anecdotal reports, uncontrolled clinical trials or prospective registries. Despite not fully conclusive, these and more recent studies, including the TELESTO trial, unravel an overall adverse action of iron overload and therapeutic benefit of chelation, ranging from improved hematological outcome, reduced transfusion dependence and superior survival of iron-loaded MDS patients. The still limited and somehow controversial experimental and clinical data available from preclinical studies and randomized trials highlight the need for further investigation to fully elucidate the mechanisms underlying the pathological impact of iron overload-mediated toxicity as well as the effect of classic and novel iron restriction approaches in MDS. This review aims at providing an overview of the current clinical and translational debated landscape about the consequences of iron overload and chelation in the setting of MDS.
first_indexed 2024-03-07T16:52:16Z
format Article
id doaj.art-996edda0954a4334863c2df46ba0b9b1
institution Directory Open Access Journal
issn 2572-9241
language English
last_indexed 2024-03-07T16:52:16Z
publishDate 2020-06-01
publisher Wiley
record_format Article
series HemaSphere
spelling doaj.art-996edda0954a4334863c2df46ba0b9b12024-03-03T04:44:28ZengWileyHemaSphere2572-92412020-06-0143e35710.1097/HS9.0000000000000357202006000-00007Controversies on the Consequences of Iron Overload and Chelation in MDSFrancesca VinchiSaskia HellUwe PlatzbeckerAbstract. Many patients with MDS are prone to develop systemic and tissue iron overload in part as a consequence of disease-immanent ineffective erythropoiesis. However, chronic red blood cell transfusions, which are part of the supportive care regimen to correct anemia, are the major source of iron overload in MDS. Increased systemic iron levels eventually lead to the saturation of the physiological systemic iron carrier transferrin and the occurrence of non-transferrin-bound iron (NTBI) together with its reactive fraction, the labile plasma iron (LPI). NTBI/LPI-mediated toxicity and tissue iron overload may exert multiple detrimental effects that contribute to the pathogenesis, complications and eventually evolution of MDS. Until recently, the evidence supporting the use of iron chelation in MDS was based on anecdotal reports, uncontrolled clinical trials or prospective registries. Despite not fully conclusive, these and more recent studies, including the TELESTO trial, unravel an overall adverse action of iron overload and therapeutic benefit of chelation, ranging from improved hematological outcome, reduced transfusion dependence and superior survival of iron-loaded MDS patients. The still limited and somehow controversial experimental and clinical data available from preclinical studies and randomized trials highlight the need for further investigation to fully elucidate the mechanisms underlying the pathological impact of iron overload-mediated toxicity as well as the effect of classic and novel iron restriction approaches in MDS. This review aims at providing an overview of the current clinical and translational debated landscape about the consequences of iron overload and chelation in the setting of MDS.http://journals.lww.com/10.1097/HS9.0000000000000357
spellingShingle Francesca Vinchi
Saskia Hell
Uwe Platzbecker
Controversies on the Consequences of Iron Overload and Chelation in MDS
HemaSphere
title Controversies on the Consequences of Iron Overload and Chelation in MDS
title_full Controversies on the Consequences of Iron Overload and Chelation in MDS
title_fullStr Controversies on the Consequences of Iron Overload and Chelation in MDS
title_full_unstemmed Controversies on the Consequences of Iron Overload and Chelation in MDS
title_short Controversies on the Consequences of Iron Overload and Chelation in MDS
title_sort controversies on the consequences of iron overload and chelation in mds
url http://journals.lww.com/10.1097/HS9.0000000000000357
work_keys_str_mv AT francescavinchi controversiesontheconsequencesofironoverloadandchelationinmds
AT saskiahell controversiesontheconsequencesofironoverloadandchelationinmds
AT uweplatzbecker controversiesontheconsequencesofironoverloadandchelationinmds