What is the treatment for Thalassemia (a genetic disorder affecting hemoglobin production)?

Treatment of Thalassemia

The cornerstone of thalassemia major treatment is regular blood transfusions to maintain pre-transfusion hemoglobin levels of 9-10 g/dL with concurrent iron chelation therapy to prevent iron overload complications. 1

Types of Thalassemia

• Thalassemia is a genetic disorder with reduced or absent production of globin chains that comprise hemoglobin, resulting in ineffective erythropoiesis, premature red blood cell destruction, and anemia 2
• Three main clinical forms of β-thalassemia exist with increasing severity: thalassemia minor (carrier state), thalassemia intermedia, and thalassemia major (severe transfusion-dependent anemia) 3
• β-thalassemia major is characterized by severe reduction or absent production of the β-globin chain, resulting in life-threatening anemia from approximately 1-2 years of age 4

Transfusion Therapy

• Blood transfusions are required lifelong in thalassemia major to suppress ineffective erythropoiesis and prolong survival 4
• Maintain pre-transfusion hemoglobin at 9-10 g/dL and post-transfusion hemoglobin at 13-14 g/dL to balance between minimizing iron loading and maximizing symptom relief 1, 4
• Regular transfusions reduce the expansion of blood volume seen in chronic anemia, which is a driver of increased cardiac index 4
• Transfusion intervals typically range between 2-4 weeks, with monitoring of hemoglobin levels every 2 weeks 5, 1
• Prestorage leukoreduction of blood products is recommended, and red blood cell antigen phenotype should be determined before the first transfusion 6

Iron Chelation Therapy

• Iron chelation must be initiated concurrently with transfusion therapy as each unit of blood contains approximately 200 mg of iron 4, 1
• Three main iron chelators are available:
  • Deferoxamine (parenteral): Recommended during periods of antiviral treatment for hepatitis C 4
  • Deferiprone (oral): Use with caution as it may increase risk of neutropenia 4
  • Deferasirox (oral): Effective for reducing liver iron concentration (LIC) and serum ferritin at doses of 20-30 mg/kg/day 7
• Iron chelation therapy should be guided by monitoring of LIC via MRI and serum ferritin levels 1, 7
• Deferasirox has been shown to improve cardiac T2* values in patients with cardiac iron overload, with geometric mean increasing from 11.98 ms at baseline to 17.12 ms after 3 years of therapy 7

Monitoring and Management of Complications

• Cardiac complications from iron overload are the most common cause of death in thalassemia major, accounting for approximately 70% of deaths 4
• Regular cardiac assessment with T2* cardiovascular magnetic resonance (CMR) is essential to detect and monitor cardiac iron overload 4, 1
• Monitor for hepatic complications, especially in patients with concurrent viral hepatitis 1
• Continuous monitoring of hematologic parameters is necessary to detect anemia and neutropenia 4
• Endocrine complications (growth failure, delayed puberty, diabetes, hypothyroidism) require regular screening and appropriate hormone replacement 2

Special Considerations for Hepatitis C Treatment

• For thalassemia patients with HCV infection, combination treatment with Peg-interferon and ribavirin is recommended 4
• Expect a 30-40% increase in transfusion requirements during HCV treatment due to ribavirin-induced hemolysis 4, 1
• Maintain hemoglobin levels above 9 g/dL during antiviral therapy 4
• Switching to deferoxamine treatment during antiviral treatment for hepatitis C is recommended, as deferiprone may increase risk of neutropenia 4
• Patients with cardiovascular diseases should be closely monitored, and those with decompensated myocardiopathy should be excluded from antiviral treatment 4

Curative Options

• Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only definitive cure for thalassemia major 1, 3
• HSCT is recommended for transfusion-dependent severe thalassemia, particularly in children aged 2-6 years before progression to stage 3 disease 1
• Gene therapy is under investigation as a potential curative approach 3

Common Pitfalls and Caveats

• Failure to initiate iron chelation therapy concurrently with transfusion therapy can lead to iron overload and organ damage 1
• Inadequate monitoring of iron levels can result in under-chelation or over-chelation, both with significant consequences 1
• Patients receiving blood at multiple hospitals within or outside their home country may have incomplete transfusion records, increasing the risk of alloimmunization 6
• Switching between chelation agents may be necessary during certain treatments (e.g., switching to deferoxamine during HCV treatment) 4, 1