What are the indications for chelation therapy in patients with iron overload?

From the Guidelines

Chelation therapy is indicated for patients with iron overload when serum ferritin levels exceed 1,000 ng/mL or when there is evidence of organ damage due to excess iron, with the goal of reducing morbidity, mortality, and improving quality of life. The primary indications for chelation therapy include:

• Transfusion-dependent anemias, such as thalassemia major and sickle cell disease
• Hereditary hemochromatosis unresponsive to phlebotomy
• Certain myelodysplastic syndromes requiring regular transfusions Treatment should begin after approximately 10-20 units of blood transfusions or when liver iron concentration exceeds 7 mg/g dry weight. The main chelating agents include:
• Deferoxamine (40-50 mg/kg/day via subcutaneous infusion over 8-12 hours, 5-7 days per week) 1
• Deferasirox (20-40 mg/kg/day orally once daily) 1
• Deferiprone (75-100 mg/kg/day orally in three divided doses) 1 Treatment efficacy is monitored through regular serum ferritin measurements, typically every 3 months, and periodic assessment of organ function 1. Chelation therapy aims to prevent complications of iron overload, such as liver cirrhosis, cardiomyopathy, endocrine dysfunction, and early mortality, by binding excess iron and facilitating its excretion through urine or feces, thereby reducing the body's iron burden and preventing further organ damage. It is essential to closely monitor patients on deferasirox therapy, including measuring their serum creatinine and/or creatinine clearance and performing liver function tests before initiation of therapy and regularly thereafter 1.

From the FDA Drug Label

Deferoxamine mesylate for injection, USP, is indicated for the treatment of acute iron intoxication and of chronic iron overload due to transfusion-dependent anemias Deferoxamine mesylate can promote iron excretion in patients with secondary iron overload from multiple transfusions (as may occur in the treatment of some chronic anemias, including thalassemia)

The indications for chelation therapy with deferoxamine in patients with iron overload are:

• Acute iron intoxication
• Chronic iron overload due to transfusion-dependent anemias, such as thalassemia, where the goal is to promote iron excretion and slow accumulation of hepatic iron 2 Key points:
• Deferoxamine is not indicated for primary hemochromatosis, as phlebotomy is the preferred method for removing excess iron in this condition.

From the Research

Indications for Chelation Therapy

The indications for chelation therapy in patients with iron overload include:

• Myelodysplastic syndromes 3
• Sickle cell disease 3
• Thalassemia 3, 4, 5, 6, 7

Iron Overload Conditions

Iron overload can result from:

• Congenital impairment of iron regulation 3
• Increased intestinal iron absorption secondary to bone marrow erythroid hyperplasia 3
• Chronic transfusional regimen 3, 7

Diagnostic Tools

Diagnostic tools for assessing body iron stores include:

• Serum ferritin measurement 3, 4, 5, 6, 7
• Liver biopsy (gold standard) 3
• Noninvasive imaging techniques 3, 5

Chelation Therapy

Chelation therapy can help lower tissue iron levels and prevent iron overload complications, improving event-free survival (EFS) 3. The decision to start chelation and which chelator to choose remains a joint decision of the clinician and patient 3. Available chelators include:

• Deferiprone 3, 4, 6
• Deferoxamine 3, 4, 6, 7
• Deferasirox 3, 4, 6