What is the treatment for thalassemia?

Treatment of Thalassemia

The cornerstone of thalassemia management is regular blood transfusions to maintain pre-transfusion hemoglobin at 9-10 g/dL combined with immediate initiation of iron chelation therapy to prevent life-threatening iron overload complications. 1

Transfusion Therapy

Initiate regular transfusion therapy immediately when the diagnosis of transfusion-dependent thalassemia is established, with the following specific targets:

• Pre-transfusion hemoglobin target: 9-10 g/dL 1
• Post-transfusion hemoglobin target: 13-14 g/dL to suppress ineffective erythropoiesis 1
• Transfusion frequency: Every 3-4 weeks to maintain these targets 1
• Monitor hemoglobin every 2 weeks, particularly during concurrent antiviral therapy or other complications 1

The rationale for maintaining higher hemoglobin levels is that supertransfusion (maintaining hematocrit >35%) actually decreases whole blood volume by approximately 21% and normalizes plasma iron turnover, ultimately reducing the rate of iron accumulation 2. While 61% of patients may have suboptimal pre-transfusion hemoglobin levels despite high transfusion volumes, adherence to these targets remains critical 3.

Iron Chelation Therapy

Start iron chelation therapy immediately upon initiating regular transfusions to prevent iron overload complications that affect cardiac, hepatic, and endocrine function 1.

Chelation Options:

• Deferasirox (oral): Starting dose of 20-30 mg/kg/day provides consistent lowering of liver iron concentration (LIC) and serum ferritin; doses below 20 mg/kg/day fail to provide consistent benefit 4
• Deferoxamine (subcutaneous/IV): 20-60 mg/kg for at least 5 days per week based on baseline LIC 5
• Deferiprone (oral): Use with caution due to increased risk of neutropenia, particularly during concurrent antiviral therapy 6, 1

Critical caveat: During antiviral treatment for hepatitis C, switch from deferiprone or deferasirox to deferoxamine, as safety data for deferasirox with combination antiviral therapy is lacking and deferiprone increases neutropenia risk 5, 6.

Monitoring Iron Burden:

• Liver iron concentration via MRI to guide chelation intensity 1
• Serum ferritin every 3 months 1
• Intensify chelation before starting antiviral treatment in patients with severe iron burden 5

Monitoring for Complications

Cardiac Assessment:

• Echocardiography and cardiac MRI T2 annually* to detect early iron-related cardiomyopathy 1
• Exclude patients with decompensated myocardiopathy or severe cardiac rhythm disorders from certain antiviral treatments due to risk of cardiac decompensation 6

Hepatic Assessment:

• Liver function tests every 3 months 1
• Ultrasound and transient elastography every 6-12 months to monitor progression from chronic hepatitis to cirrhosis 5

Endocrine Evaluation:

• Annual screening for diabetes, thyroid dysfunction, and hypogonadism 1

Management of Viral Hepatitis in Thalassemia

Hepatitis C:

Combination therapy with pegylated interferon plus ribavirin is recommended for patients with chronic HCV hepatitis or compensated cirrhosis 5:

• Duration: 48 weeks for genotypes 1 or 4; 24 weeks for genotypes 2 or 3 5, 1
• Discontinue after 12 weeks if HCV-RNA has not decreased by at least 2 log units in genotype 1 or 4 patients 5
• Expect 30-40% increase in transfusion requirements during antiviral therapy to maintain hemoglobin >9 g/dL 5, 1
• Switch to deferoxamine chelation during HCV treatment 5, 1
• Do not use erythropoietin for anemia management during antiviral therapy 5, 6
• Administer G-CSF if severe neutropenia (absolute neutrophil count <500/mm³) develops from interferon 5

Hepatitis B:

Three treatment options exist based on HBeAg status 5:

• Finite 48-week course of pegylated interferon or nucleoside/nucleotide analogs (NUCs) for HBeAg-positive patients with high ALT, low HBV DNA, and genotype A or B 5
• Long-term NUC therapy with tenofovir or entecavir as first-line monotherapy for HBeAg-positive patients without HBe seroconversion or HBeAg-negative patients, due to rapid HBV DNA reduction and high barrier to resistance 5

Common Pitfalls

• Undertransfusion: Over 60% of patients have low pre-transfusion hemoglobin despite receiving large transfusion volumes; this is particularly problematic in hemoglobin E β-thalassemia patients who require specific attention 3
• Delayed chelation initiation: Iron chelation must begin immediately with regular transfusions, not after iron overload develops 1
• Continuing deferiprone during antiviral therapy: This significantly increases neutropenia risk and should be avoided 5, 6
• Adolescent adherence: Ensuring adherence to transfusion and chelation therapy during adolescence is a universal challenge across all resource settings 7

Curative Options

Bone marrow transplantation and gene therapy represent the only curative options but remain unavailable in many countries with stressed economies 7, 8. These should be considered when available and appropriate for the individual patient's clinical situation.