What is the management of thalassemia, particularly beta-thalassemia major?

From the Guidelines

The management of beta-thalassemia major requires lifelong regular blood transfusions combined with iron chelation therapy to prevent iron overload complications and improve quality of life. Patients typically need transfusions every 2-4 weeks to maintain hemoglobin levels above 9-10 g/dL, which suppresses ineffective erythropoiesis and allows for normal growth and development 1. Iron chelation therapy should begin after approximately 10-20 transfusions or when serum ferritin exceeds 1,000 ng/mL. The three main chelating agents are deferoxamine (20-40 mg/kg/day subcutaneously over 8-24 hours, 5-7 days weekly), deferasirox (20-40 mg/kg/day orally once daily), and deferiprone (75-100 mg/kg/day orally in three divided doses) 1.

Key Components of Management

• Regular monitoring includes complete blood counts, liver and kidney function tests, ferritin levels, cardiac MRI for iron assessment, and endocrine evaluations 1.
• Splenectomy may be considered for patients with hypersplenism causing increased transfusion requirements.
• Hematopoietic stem cell transplantation offers the only curative option, with best outcomes when performed early in life with HLA-matched siblings.
• Newer therapies include luspatercept to reduce transfusion requirements and gene therapy approaches that are showing promise.
• Comprehensive care also requires management of complications like endocrine disorders, cardiac issues, and osteoporosis, along with psychosocial support and genetic counseling for families.

Iron Chelation Therapy

• Deferoxamine has a high affinity to bind with the trivalent ferric ion and is thought to remove cardiac iron by direct interaction with this ion 1.
• Deferiprone is a bidentate chelating agent with good oral bioavailability, but its long-term efficacy and safety have not been fully established 1.
• Deferasirox is a tridentate lipophilic oral chelating agent that selectively binds to iron, but long-term safety and efficacy beyond 1 year are lacking 1.

Cardiac Complications

• Heart failure is the most common cause of death in beta-thalassemia major, primarily resulting from cardiac iron accumulation 1.
• Cardiac T2* magnetic resonance is essential for estimating cardiac iron and predicting the development of heart failure 1.
• Acute decompensated heart failure requires urgent consultation with a center with expertise in its management and treatment with high-dose intravenous deferoxamine 1.

From the FDA Drug Label

The primary efficacy study, Study 1 (NCT00061750), was a multicenter, open-label, randomized, active-comparator control study to compare deferasirox tablets for oral suspension and deferoxamine in patients with beta-thalassemia and transfusional hemosiderosis Patients greater than or equal to 2 years of age were randomized in a 1:1 ratio to receive either oral deferasirox tablets for oral suspension at starting doses of 5,10,20, or 30 mg per kg once daily or deferoxamine at starting doses of 20 to 60 mg per kg for at least 5 days per week based on LIC at baseline Reduction of LIC and serum ferritin was observed with deferasirox tablet for oral suspension doses of 20 to 30 mg per kg per day. Therefore, a starting dose of 20 mg per kg per day is recommended [see Dosage and Administration (2. 1)].

The management of beta-thalassemia major involves the use of iron chelators such as deferasirox to reduce liver iron concentration (LIC) and serum ferritin levels.

• The recommended starting dose of deferasirox is 20 mg per kg per day.
• Deferasirox has been shown to be effective in reducing LIC and serum ferritin levels in patients with beta-thalassemia major 2.
• Patients with beta-thalassemia major should be treated with deferasirox under the guidance of a healthcare professional, with regular monitoring of LIC and serum ferritin levels to adjust the dose as needed.

From the Research

Management of Thalassemia

The management of thalassemia, particularly beta-thalassemia major, involves several key components, including:

• Blood transfusions: Regular blood transfusions are the cornerstone of treatment for beta-thalassemia major, with the goal of maintaining a hemoglobin level between 9-10 g/dL 3, 4.
• Iron chelation therapy: Iron chelation therapy is essential to prevent iron overload, which can lead to cardiac failure and other complications 5, 6.
• Monitoring and prevention of complications: Patients with thalassemia are at risk of various complications, including bone marrow expansion, extramedullary hematopoiesis, and iron deposition in peripheral tissues 5.

Blood Transfusion Therapy

Blood transfusion therapy is a critical component of thalassemia management, with the following key points:

• Transfusion regimen: A moderate transfusion regimen with a target pretransfusion hemoglobin level between 9-10 g/dL may reduce iron loading and allow for more effective prevention of iron overload 3.
• Transfusion volume: High transfusion volumes (>200 mL/kg/year) may be required to maintain adequate hemoglobin levels, particularly in patients with hemoglobin E beta-thalassemia 4.
• Risks and challenges: Blood transfusions carry risks, including alloimmunization, transfusion-transmitted infections, and iron overload, highlighting the need for careful monitoring and management 6.

Other Therapeutic Strategies

Other therapeutic strategies for thalassemia management include:

• Hydroxyurea: Hydroxyurea may be used to reduce the frequency of blood transfusions and improve hemoglobin levels 5.
• Hematopoietic stem cell transplantation: Hematopoietic stem cell transplantation may be considered for patients with severe thalassemia, particularly those with beta-thalassemia major 5.
• Luspatercept: Luspatercept is a novel therapy that may reduce the need for blood transfusions in patients with beta-thalassemia 5.