Treatment Strategies for Beta Thalassemia
Regular blood transfusions are vital for patients with beta thalassemia. In particular, transfusions have been shown to offset the effects of chronic anemia, thereby inhibiting the development of bone malformations, promoting normal growth and activity, and positively impacting patient quality of life.
The decision to initiate blood transfusions should be made after evaluating anemia and symptom status. Relevant considerations include reduced quality of life, failure to thrive, and other comorbidities, such as extramedullary hematopoiesis and organ dysfunction.
Nondisease-specific guidelines recommend initiating transfusions at hemoglobin (Hb) levels of 60 g/L to 100 g/L, subject to patient comorbidities, while disease-specific guidelines recommend administering leukoreduced packed red blood cells comprising a total hemoglobin content of at least 40 g.
“Thalassaemia International Federation, UK, and US guidelines recommend initiating blood transfusions at an Hb threshold of 70 g/L (measured on 2 occasions approximately 2 weeks apart, excluding other causes for the anemia), or [at] the presence of clinical complications irrespective of Hb level,” the reviewers wrote.
Iron chelation therapy is a key supportive care intervention for patients undergoing regular blood transfusions. Chronic transfusions eventually result in iron accumulation, which can lead to cardiac toxicity and death. As a result, the availability of iron chelation therapy is important in preventing these harmful effects and improving life expectancy in these patients.
Hematopoietic stem cell transplantation (HSCT) is the only curative treatment strategy for patients with beta thalassemia major. The procedure has been shown to improve patient quality of life but may have limited availability due to significant risks of morbidity and mortality, absence of matched donors, patient age, and high costs associated with treatment.
In addition to those discussed, other novel agents are being studied for potential efficacy in beta thalassemia. Recently, an investigational erythroid maturation therapy, luspatercept, showed promise in phase 2 and 3 studies for improving anemia and reducing the need for transfusions. TMPRSS6 inhibitors and hepcidin mimetics have also demonstrated positive initial results in some preclinical studies.
“Phase 3 trials are ongoing to determine the potential of gene therapy in treating beta thalassemia, and gene editing approaches are currently in full preclinical development,” the reviewers wrote.
Many of these emerging therapies may be approved for clinical use in the near future.
1. Shah FT, Sayani F, Trompeter S, Drasar E, Piga A. Challenges of blood transfusions in β-thalassemia [published online July 6, 2019]. Blood Rev. doi:10.1016/j.blre.2019.100588