What is the primary treatment for a patient with thalassemia beta?

Treatment of Beta Thalassemia

Primary Treatment Strategy

The cornerstone of beta thalassemia major management is regular blood transfusions every 3-4 weeks to maintain pre-transfusion hemoglobin at 9-10 g/dL and post-transfusion hemoglobin at 13-14 g/dL, combined with immediate initiation of iron chelation therapy to prevent life-threatening iron overload complications. 1

Transfusion Management

Initiation and Targets

• Begin regular transfusions immediately when diagnosis of transfusion-dependent thalassemia is established, with the goal of raising hemoglobin above 9 g/dL 1
• Establish a transfusion schedule every 3-4 weeks to maintain consistent hemoglobin levels 1, 2
• Target pre-transfusion hemoglobin of 9-10 g/dL to balance iron loading minimization with symptom control 3, 1
• Target post-transfusion hemoglobin of 13-14 g/dL to suppress ineffective erythropoiesis and reduce cardiac stress from chronic anemia 3, 1, 2

Rationale for Moderate Transfusion Strategy

• This moderate transfusion regimen (9-10 g/dL pre-transfusion) reduces blood consumption by approximately 24% compared to hypertransfusion protocols while still effectively suppressing erythropoiesis 4
• The moderate approach allows more effective prevention of iron loading and increases likelihood of spontaneous pubertal development without producing excessive erythroid marrow expansion 4

Iron Chelation Therapy

Initiation Timing

• Start iron chelation immediately when regular transfusions are established, as each unit of blood contains 200-250 mg of iron with no physiological excretion mechanism 2
• Do not delay chelation therapy, as iron overload is the leading cause of death in thalassemia, accounting for approximately 70% of mortality 3

First-Line Chelation Options

• Deferoxamine: 50 mg/kg/day subcutaneously 5-7 nights per week 2
• Deferiprone: 75 mg/kg/day orally (use with caution due to neutropenia risk) 1
• Deferasirox: Starting dose 20-30 mg/kg/day orally based on liver iron concentration 2, 5

Chelation Monitoring and Adjustments

• Target serum ferritin <1000 mcg/L, though MRI is more accurate than ferritin alone for assessing iron burden 1
• Monitor liver iron concentration (LIC) via MRI to guide chelation therapy intensity 1, 2
• Deferasirox doses of 20-30 mg/kg/day provide consistent lowering of LIC and serum ferritin, while doses below 20 mg/kg/day fail to provide consistent reduction 5

Comprehensive Monitoring Protocol

Cardiac Surveillance

• Cardiac MRI T2 annually* to detect cardiac iron before symptoms develop (T2* values <10 ms indicate severe cardiac iron overload, 10-20 ms indicate mild-moderate overload) 3, 1, 2
• Echocardiography annually to assess left ventricular ejection fraction 2
• Cardiac iron overload remains the most common cause of death in thalassemia, with typical age at cardiac death being 35 years even with deferoxamine treatment 3

Hepatic Monitoring

• Liver function tests every 3 months to detect hepatotoxicity from iron overload or chelation therapy 1
• Screen for hepatitis B and C at baseline and periodically, as chronic viral hepatitis is common in transfused patients 1, 2

Endocrine Surveillance

• Annual screening for diabetes, thyroid dysfunction, and hypogonadism, as endocrinopathies develop from iron deposition in endocrine glands 1

Hematologic Monitoring

• Hemoglobin levels every 2 weeks during periods of antiviral treatment or when adjusting transfusion schedules 1
• Serum ferritin every 3 months as a trend marker for iron burden 2

Management of Viral Hepatitis Complications

Hepatitis C Treatment

• Combination therapy with Peg-interferon plus ribavirin for HCV-positive patients with chronic hepatitis or compensated cirrhosis 3, 1
• Duration: 48 weeks for genotypes 1 or 4; 24 weeks for genotypes 2 or 3 3, 2
• Anticipate 30-40% increase in transfusion requirements during antiviral therapy due to ribavirin-induced hemolysis 1, 2
• Switch to deferoxamine during antiviral treatment, as deferiprone increases neutropenia risk and deferasirox safety data during concurrent antiviral therapy is limited 3
• Withdraw antiviral therapy after 12 weeks if serum HCV-RNA has not decreased by at least 2 log units in genotype 1 or 4 patients 3

Hepatitis B Treatment

• Three treatment options exist: finite 48-week course with Peg-interferon, finite course with nucleoside/nucleotide analogs (NUCs), or long-term NUCs 3
• Tenofovir or entecavir as first-line monotherapy for long-term treatment due to rapid HBV DNA reduction and high barrier to resistance 3

Critical Pitfalls to Avoid

Cardiac Complications

• Never delay cardiac assessment in symptomatic patients—cardiac iron overload can present with seizures and has 50% one-year mortality if untreated 1
• Exclude patients with decompensated myocardiopathy or severe arrhythmias from antiviral therapy 3, 1
• Avoid aggressive diuretic therapy in heart failure, as thalassemia patients require adequate preload 1

Chelation Errors

• Do not use deferiprone during concurrent antiviral therapy due to compounded neutropenia risk 3, 1
• Intensify chelation treatment before starting antiviral therapy in patients with severe iron burden 3
• Monitor for neutropenia (absolute neutrophil count <500/mm³) and administer granulocyte colony-stimulating factor if needed during interferon treatment 3

Transfusion Management During Antiviral Therapy

• Maintain hemoglobin >9 g/dL during antiviral treatment by increasing transfusion frequency 3
• Do not use erythropoietin for anemia management during antiviral therapy 3

Curative Treatment Option

• Hematopoietic stem cell transplantation (HSCT) is the only cure and should be performed as early as possible, ideally before age 14 years and before iron-related organ damage develops 2
• Optimize iron chelation before bone marrow transplant to reduce non-relapse mortality 1