Hematopoietic stem cell transplantation for sickle cell disease: results, indications and prospect

Despite progress made in sickle cell anemia (SCA) management, such as the prevention of pneumococcal infections, the introduction of hydroxyurea and transfusions therapy, the SCA remains a disease with high risk of morbidity and early death. Myeloablative, HLA-identical hematopoietic transplantation, proposed in France since 25 years for sickle cell anemia children and young adults offers now 97% chances of cure. The transplant-related-mortality (TRM) and rejection rate have been reduced to less than 2% with antithymocyte globulin (ATG) and less than 1% are alive with extensive chronic graft vs-host disease (GvH). These excellent results have encouraged to extend indications to patients with less severe disease, in particular to children detected at risk of stroke by transcranial Doppler. Moreover, in USA, non-myeloablative conditioning regimens have allowed the extension to adults with genoidentical donor and some degree of organ dysfunction and cure was obtained in 87% of them and no GvH. Nevertheless, the results with unrelated donors are not sufficient because the HLA-disparity between the donors of the world-bank and the SCA-patients. The results of haplo-identical transplantations with cyclophosphamide post-transplant are interesting because offering access to transplantation to almost all SCA-patients with a low GvH risk and chances of cure of about 60-70%. Gene therapy results are promising for these SCA-patients who all could be potential candidates.