Stem cells in the treatment of sickle cell disease

Abstract

Sickle Cell Disease (SCD) is autosomal recessive disorder that is the result of a point mutation in the coding region of the beta globin gene. Polymerization of red blood cells with the sickle hemoglobin result in painful clinical symptoms and early death due to end organ failure. Improvement of treatment has extended the survival of adolescents into adulthood and offers relief of symptoms but does not offer a cure against the diagnosis being the inevitable cause of an early death. In addition, response to therapies vary between patients depending on their responsiveness and metabolism of medications. Hematopoietic stem cell transplantation offers reduction of recipient Hb S through replacing it with Hb A from the donor. Increased use of hematopoietic stem cell transplantation (HSCT) offers a curative therapy for patients with SCD that have access to an HLA-identical donor. However, limitations to indications for HSCT result due to associated toxicities with myeloablative conditioning and risk of graft failure. Reduced intensity and non-myeloablative conditioning look at reducing associated toxicities and making HSCT readily available for the adult population through mixed chimerism. In addition, clinical trials looking at alternative donors and gene therapies expand the availability of HSCT for the vast majority of patients without an HLA-identical donor.