title: Hematopoietic stem cell transplantation for sickle cell disease: state of the science.
abstract: Sickle cell disease (SCD) is an inherited disorder secondary to a point mutation at the sixth position of the beta chain of human hemoglobin resulting in the replacement of valine for glutamic acid. This recessive genetic abnormality precipitates the polymerization of the deoxygenated form of hemoglobin S inducing a major distortion of red blood cells (S-RBC), which decreases S-RBC deformability leading to chronic hemolysis and vaso-occlusion. These processes can result in severe complications including chronic pain, end-organ dysfunction, stroke, and early mortality. The only proven curative therapy for patients with SCD is myeloablative conditioning and allogeneic stem cell transplantation from HLA-matched sibling donors. In this review, we discuss the most recent advances in allogeneic stem cell transplantation in patients with SCD including more novel approaches such as reduced toxicity conditioning and the use of alternative allogeneic donors, including matched unrelated donors (MUDs), unrelated cord blood donors (UCBT), and familial haploidentical (FHI) donors. The results to date are very encouraging regarding allogeneic stem cell transplantation for patients with SCD including high survival rates and enabling a greater number of patients suffering from this chronic and debilitating condition to receive curative allogeneic stem cell therapies. However, we still have several areas to investigate and barriers to overcome to successfully cure the majority of patients with severe SCD through allogeneic stem cell therapies.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Julie-An
authors.initials: JA
authors.lastname: Talano
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D059350:Chronic Pain / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D036101:Cord Blood Stem Cell Transplantation; D018380:Hematopoietic Stem Cell Transplantation; D006451:Hemoglobin, Sickle / Q000737:chemistry / Q000378:metabolism; D006650:Histocompatibility Testing; D006801:Humans; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D066263:Protein Aggregation, Pathological / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D035781:Siblings; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D006451:Hemoglobin, Sickle; D019653:Myeloablative Agonists
keywords: allogeneic hematopoietic stem cell transplantation; familial haploidentical transplantation; reduced toxicity conditioning; sickle cell disease