Recent Advances in the Pathophysiology and Therapeutic Management of Thalassemia: A Comprehensive Review
DOI:
https://doi.org/10.48047/tw5tza77Keywords:
Thalassemia, β-thalassemia, ineffective erythropoiesis, iron overload, gene therapy, luspatercept, hepcidin, transfusion, chelation therapyAbstract
Thalassemia represents a diverse group of inherited hemoglobinopathies characterized by reduced or absent synthesis of α- or β-globin chains, leading to chronic anemia, ineffective erythropoiesis, and iron overload. Over the past decade, significant progress has been made in understanding the complex molecular and cellular mechanisms underlying thalassemia, particularly in β-thalassemia major and intermedia. Advances in pathophysiology have elucidated the roles of hepcidin suppression, oxidative stress, dysregulated erythroid maturation, and inflammatory signaling in disease progression. These insights have driven the development of innovative therapeutic strategies that go beyond traditional transfusion and iron chelation therapy.
Emerging treatments include gene therapy approaches, such as lentiviral vector-based gene addition and CRISPR-Cas9-mediated genome editing, which offer curative potential. Additionally, novel agents like luspatercept, an erythroid maturation agent, and hepcidin agonists represent promising tools in managing ineffective erythropoiesis and iron dysregulation. While hematopoietic stem cell transplantation remains the only widely accepted curative option, limitations in donor availability and transplant-related risks have restricted its use. This review comprehensively synthesizes recent advances in the pathophysiology and therapeutic landscape of thalassemia, highlighting both established and emerging treatment modalities. It also discusses clinical trial data, implementation challenges, and future directions toward personalized and globally accessible care for individuals affected by thalassemia.
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