Sickle Cell Anemia: Therapeutic Advances, Disease-Modifying Therapies, and Future Prospects

Abstract

Introduction: Sickle cell disease is the most prevalent inherited hemoglobinopathy worldwide, characterized by chronic hemolysis, systemic inflammation, and recurrent episodes of vaso-occlusion, which are responsible for high morbidity and mortality. In recent decades, therapeutic advances have expanded treatment options, including disease-modifying therapies, hematopoietic stem cell transplantation, and gene therapy. Objective: To analyze the scientific evidence regarding therapeutic advances, disease-modifying therapies, and future prospects for the treatment of sickle cell anemia. Methods: A systematic review conducted in accordance with PRISMA guidelines, using the databases PubMed, Scopus, Web of Science, Embase, the Cochrane Library, and ScienceDirect. Studies published between 2016 and 2026 were included, covering pharmacological therapies, hematopoietic stem cell transplantation, gene therapy, and gene editing. After the selection process, 124 studies comprised the final sample. Results: Hydroxyurea remained the primary disease-modifying drug, while crizanlizumab, voxelotor, and L-glutamine demonstrated additional benefits in reducing vaso-occlusive crises, hemolysis, and clinical complications. Hematopoietic stem cell transplantation showed the greatest curative potential, and gene therapies based on lentiviral vectors and CRISPR-Cas9 revealed promising results in terms of reducing clinical events and achieving transfusion independence. However, limitations related to cost, specialized infrastructure, access, and the lack of long-term follow-up still restrict their widespread implementation. Conclusion: The evidence demonstrates that advances in disease-modifying therapies and potentially curative strategies are transforming the management of sickle cell disease, reinforcing the need for long-term studies and public policies that expand access to innovative technologies.