[What is your diagnosis? Inveterate anterior shoulder dislocation].

Area of Science:

• Hematology
• Genetics
• Pharmacology

Context:

• Sickle cell disease (SCD) is a prevalent genetic disorder in France, causing significant morbidity and premature mortality.
• Current first-line treatments like hydroxyurea may be insufficient for severe cases or those with complications such as cerebral vasculopathy.

Purpose:

• To review current and emerging therapeutic strategies for sickle cell disease.
• To highlight the curative potential of hematopoietic stem cell transplantation and the advancements in gene therapy.

Summary:

• Beyond hydroxyurea, new agents like voxelotor and crizanlizumab offer alternatives. Hematopoietic stem cell (HSC) transplantation, particularly allogeneic transplantation in childhood, remains the only curative option.
• Reduced-intensity conditioning for adult HSC transplantation and ongoing gene therapy trials using autologous genetically modified HSCs are expanding treatment possibilities.
• Despite progress, challenges persist, including the toxicity of myeloablative conditioning (e.g., induced sterility) and the risk of graft-versus-host disease in allogeneic transplantation.

Impact:

• These advancements offer hope for improved outcomes and potential cures for sickle cell disease patients.
• Understanding the benefits and limitations of each therapeutic approach is crucial for clinical decision-making.
• Further research into gene therapy and optimized transplantation protocols may overcome current treatment barriers.