Update on Iron Chelators in Thalassemia

Abstract

Over the past four decades, there have been dramatic improvements in survival for patients with thalassemia major due in large measure to improved iron chelators. Two chelators are approved for use in the United States and Canada, parenteral deferoxamine and oral deferasirox. Three are available in much of the rest of the world, where oral deferiprone is also approved (in the United States, deferiprone is only available in studies, for emergency use, or on a "compassionate-use" basis). Many trials and worldwide clinical experience demonstrate that each of the three drugs can chelate and remove iron, and thereby prevent or improve transfusional hemosiderosis in thalassemia patients. However, the chelators differ strikingly in side-effect profile, cost, tolerability and ease of adherence, and (to some degree) efficacy for any specific patient. The entire field of chelator clinical trials suffers from the fact that each drug (as monotherapy or in combination) has not been tested directly against all of the other possibilities. Acknowledging the challenges of assessing chelators with diverse properties and imperfect comparative data, the purpose of this review is to summarize the last 4 years of studies that have improved our understanding of the applications and limitations of iron chelators in various settings for thalassemia patients, and to point out areas for much-needed future research.

Inhibitory effect of iron withdrawal by chelation on the growth of human and murine mammary carcinoma and fibrosarcoma cells

“…Iron chelation therapy may also benefit patients receiving anthracycline anticancer drugs such as doxorubicin since iron has a widely recognized role in the development of treatment-limiting anthracycline-mediated cardiotoxicity (Gammella et al, 2014). Unfortunately, iron chelators that are currently approved for clinical use have shortcomings such as adverse side effects, short half-life, and high cost (Neufeld, 2010). The development of improved iron chelators is therefore of considerable interest.…”

“…However, iron chelators (deferasirox, deferoxamine, and deferiprone) that are currently available for clinical use have limitations such as adverse side effects, short biological half-life, and high cost (Neufeld, 2010). DIBI is a novel highly selective iron chelator that is a member of a family of soluble copolymers with selectable molecular weights and defined contents of the modified hydroxypyridinone iron chelator, 3-hydroxy-1-(β-methacrylamidoethyl)-2-methyl-4(1 H)-pyridinone (MAHMP) (Holbein and Mira de Orduña, 2010).…”

Combined treatment of 3-hydroxypyridine-4-one derivatives and green tea extract to induce hepcidin expression in iron-overloaded β-thalassemic mice

“…Effective iron chelators are required to remove this iron to prevent oxidative damage in the vital organs, particularly the heart and liver. Nowadays, deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are the iron chelators which are usually used for the treatment of β-thalassemia patients with iron overload; however, they do produce adverse effects [4].…”

A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation

“…1 The optimization of both erythrocyte transfusion and iron chelating therapy has resulted in a remarkable improvement in the life expectancy of patients with TM. 2,3 However, complications related to iron overload cannot be completely managed through chelating therapy, and compliance with a chronic transfusion regimen is difficult to maintain throughout a lifetime. The only curative therapy remains the replacement of the defective erythropoiesis by allogeneic hematopoietic stem cell transplantation (HSCT).…”