What is the role of medications in the treatment of beta thalassemia?

Updated: Dec 19, 2018
  • Author: Pooja Advani, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Medical therapy for beta thalassemia primarily involves iron chelation. Each unit of transfused red blood cells (RBCs) contains approximately 200 mg of elemental iron. Additionally, anemia and ineffective erythropoiesis down-regulates the synthesis of hepcidin. [31, 32]

The objective of iron chelation is to avoid the complications of iron overload such as cardiac and hepatic dysfunction. Chelation therapy significantly improves myocardial T2* (a magnetic resonance technique for assessing tissue iron concentration) and left ventricular function. [33, 34]

The following chelation agents are approved for use in the United States:

  • Deferoxamine – Intravenously administered
  • Deferiprone – Orally administered; indicated for patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate. 
  • Deferasirox [35]  – Orally administered; approved for treatment of chronic iron overload due to multiple blood transfusions and non–transfusion-dependent thalassemia

A study in 197 beta thalassemia major patients who had evidence of myocardial siderosis (T2* 6-20 ms) but no sign of cardiac dysfunction reported that deferasirox was noninferior to subcutaneous deferoxamine for myocardial iron removal (assessed by improvement in myocardial T2*). [36]  

Deferiprone is particularly effective for cardiac iron removal and is therefore recommended for use in patients with significant cardiac iron loading or iron-related cardiac disease. The adverse effects of most concern are agranulocytosis and milder forms of neutropenia. [37]  In clinical trials, agranulocytosis has occurred in 1.5% of patients taking deferiprone, most often during the first year of therapy. Weekly monitoring of the absolute neutrophil count allows early detection of granulocytosis, so that therapy can be interrupted. [38]  

A comparison study by Poggi et al in 165 adults with beta thalassemia major found benefits of deferasirox compared with other iron chelation regimens (deferoxamine, deferiprone, alone or in combination). After 5 consecutive years of therapy, patients on deferasirox had the highest decrease in the prevalence of any endocrinopathy (diabetes mellitus, hypothyroidism, or hypogonadism) A significant increase in mean bone mineral density T-score (P <  0.001) and a considerable decrease in osteoporosis prevalence were observed in patients receiving deferasirox but not other chelators. [39]  

Combinations of deferasirox with other chelating agents have also been evaluated. The combination of deferasirox and deferiprone produced a higher reduction in serum ferritin, greater improvement in cardiac T2* and quality of life indices, and better compliance compared with the combination of deferoxamine and deferiprone. [40]

 Guidelines on chelation treatment in thalassemia major have been published. [41, 42]  In general, iron chelation is started at age 2-4 years after 20-25 RBC units have been transfused, in patients with a serum ferritin level of greater than 1000 μg/dL and a liver iron concentration (LIC) of greater than 3 mg iron/g dry weight as measured by liver biopsy or by hepatic T2* on magnetic resonance imaging. [12]

Starting iron chelation therapy earlier had been avoided because of concerns over toxicity from deferoxamine; however, this may increase the risk of toxicity from iron accumulation. However, Elalfy et al reported that chelation with deferiprone, which has a lower affinity for iron than deferoxamine, could postpone transfusional iron overload while maintaining a good safety profile. [43]  

In their study, 61 patients with transfusion-dependent thalassemia, aged 10 to 18 (median 12) months, with serum ferritin levels between 400 and 1000 ng/mL, were randomized to early chelation with low-dose (50 mg/kg/day) of deferiprone or to delayed chelation. By approximately 6 months after randomization, none of the patients in the early-chelation arm, but all of those in the delayed-chelation arm, had serum ferritin levels >1000 ng/mL and transferrin saturation levels >70%. None of the patients in the early-chelation arm experienced unexpected, serious, or severe adverse events. [43]


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