[Therapeutic approaches in sickle cell disease]

THERAPEUTIC APPROACHES IN SICKLE CELL DISEASE. Sickle cell disease, the most common genetic disease in France, is still burdened with morbidity and early mortality before the age of 50. When the first-line treatment, hydroxyurea, is insufficient or in the case of organic damage(s) (in particular cerebral vasculopathy), a therapeutic intensification must be considered. New molecules are now available, such as voxelotor and crizanlizumab, but only hematopoietic stem cell (HSC) transplantation can cure the disease. Allogeneic HSC transplantation during childhood with a sibling donor is the reference but it is now possible to perform this procedure in adults with a reduced pre-transplant conditioning. Gene therapy, which consists of an autograft of genetically modified HSCs, has obtained promising results but has not yet demonstrated a complete cure of the disease (protocols underway). The toxicity of myeloablative conditioning (used in pediatrics or for gene therapy), particularly the sterility induced, and the risk of graft-versushost disease (for allogeneic transplantation) are limiting factors of these treatments.