Iron Chelation in Thalassemia Major

Borgna‐Pignatti, Caterina; Marsella, Maria

doi:10.1016/j.clinthera.2015.10.001

Cited by 55 publications

(52 citation statements)

References 65 publications

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“…In the following decades, the oral iron chelators deferiprone (DFP)149 and deferasirox (DFX)150 were developed and approved for the treatment of iron overload, improving iron chelation therapy patient satisfaction as compared to treatment with DFO151. Both DFO and DFX are currently recommended as first-line chelation therapy in iron overload, but the toxicity profile of these compounds, which include hypersensitivity reactions, liver dysfunction, renal dysfunction and neuronal hearing loss152, warrant further developments in iron chelation therapies. For example, in preclinical models of iron-loading anaemia, the administration of unmodified Tf, which can be considered the physiological iron chelator, has effectively redistributed iron to developing erythroid cells153.…”

Section: Iron Metabolism As a Therapeutic Targetmentioning

confidence: 99%

Targeting iron metabolism in drug discovery and delivery

Crielaard

Lammers

Rivella

2017

Nat Rev Drug Discov

279

205

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Iron fulfils a central role in many essential biochemical processes in human physiology, which makes proper processing of iron crucial. Although iron metabolism is subject to relatively strict physiological control, in recent years numerous disorders, such as cancer and neurodegenerative diseases, have been linked to deregulated iron homeostasis. Because of its involvement in the pathogenesis of these diseases, iron metabolism constitutes a promising and largely unexploited therapeutic target for the development of new pharmacological treatments. Several iron metabolism-targeted therapies are already under clinical evaluation for haematological disorders, and these and newly developed therapeutic agents will likely have substantial benefit in the clinical management of iron metabolism-associated diseases, for which few efficacious treatments are often available.

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Section: Iron Metabolism As a Therapeutic Targetmentioning

confidence: 99%

Targeting iron metabolism in drug discovery and delivery

Crielaard

Lammers

Rivella

2017

Nat Rev Drug Discov

279

205

View full text Add to dashboard Cite

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“…Various professional organizations have identified target populations that might benefit from HCC surveillance plans, but the risk factors in the thalassemia population are not clearly outlined in those recommendations. On the basis of current evidence, it is suggested that high‐risk patients with thalassemia should undergo biannual liver ultrasound for HCC screening, with high‐risk patients identified as patients with HCV and/or HBV infection, NTDT with LIC ≥5 mg Fe/g dry weight (dw), TDT with LIC ≥7 mg Fe/g dw or serum ferritin ≥1000 ng/mL, or advanced cirrhosis …”

Section: Managementmentioning

confidence: 99%

“…Patients with thalassemia who are iron overloaded should receive chelation therapy . Table outlines the different iron‐chelation strategies and their indications in the TDT and NTDT syndromes . It is also important to mention that blood transfusions, in light of their putative immunomodulatory effects, should be restricted to guidelines in TDT and only to instances when they are indicated in NTDT.…”

Section: Managementmentioning

confidence: 99%

Hepatocellular carcinoma as an emerging morbidity in the thalassemia syndromes: A comprehensive review

Moukhadder

Halawi

Cappellini

et al. 2016

Cancer

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The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is on the rise. The 2 well recognized HCC risk factors in thalassemia are iron overload and chronic viral infection with hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, which results in genotoxicity, and to immunologic dysregulation, which attenuates cancer immune surveillance. Chronic hepatitis B and C infections lead to necroinflammation, which can prompt progression to HCC, but an independent role of hepatitis B virus in hepatic carcinogenesis among patients with thalassemia has not been demonstrated. Screening patients who have thalassemia using magnetic resonance imaging-based liver iron concentration measurement and liver ultrasound is recommended for early detection of iron overload and HCC, respectively. Prevention primarily resides in hepatitis B vaccination, donor blood screening, hepatitis treatment, and iron chelation. Although solid data is lacking on the outcomes of HCC treatment in patients with thalassemia, a personalized approach tailored to the individual patient's comorbidities remains necessary for treatment success. Treatment modalities for HCC include surgical resection, chemoembolization, and liver transplantation, among others. Multicenter studies are needed to better explore therapeutic targets that can improve the prognosis of these patients. Cancer 2017;123:751-58. © 2016 American Cancer Society.

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“…Excessive iron is deposited in almost all tissues but primarily in the liver, the heart and the endocrine glands. Early introduction of the chelating agent to prevent iron overload in vulnerable organs leads to improved life expectancy (54). TM patients often present multiple endocrine dysfunctions: growth failure, hypogonadism, diabetes, hypothyroidism, hypoparathyroidism and, less u n c o r r e c t e d p r o o f frequently, hypoadrenalism (8, [55][56][57].…”

Section: Iron Overload In Endocrine Glandsmentioning

confidence: 99%

Pathogenesis of Thalassemia Major–Associated Osteoporosis: Review of the Literature and Our Experience

Gaudio¹,

Morabito²,

Catalano³

et al. 2018

Jcrpe

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Due to increasing life expectancy in thalassemia major (TM), osteoporosis is emerging as a significant problem. Its aetiology is multifactorial, culminating in increased bone resorption and remodelling. Hypogonadism and marrow expansion seem to play an important role, but iron overload, deferoxamine toxicity, a defective GH-IGF-1 axis and multiple endocrinopathies may represent additional causes of bone damage. Many of these patients, though under appropriate treatment programs, do not achieve normal peak bone mass. The RANK/RANKL/OPG and the Wnt/βCatenin systems work as major mediators of imbalanced bone turnover and bone loss. Additional genetic factors, such as collagen type I alpha 1 and vitamin D receptor gene polymorphisms, may exert some influence on the enhanced fracture risk observed in TM. To date, in spite of adequate hormone replacement, chelating therapy, and acceptable haemoglobin levels, subjects with TM display impaired bone density and imbalanced bone turnover, so the puzzle of the pathogenesis of thalassemia major-induced osteoporosis remains far from being solved.

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Iron Chelation in Thalassemia Major

Cited by 55 publications

References 65 publications

Targeting iron metabolism in drug discovery and delivery

Targeting iron metabolism in drug discovery and delivery

Hepatocellular carcinoma as an emerging morbidity in the thalassemia syndromes: A comprehensive review

Pathogenesis of Thalassemia Major–Associated Osteoporosis: Review of the Literature and Our Experience

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