title: Advances in stem cell transplantation and gene therapy in the β-hemoglobinopathies.
abstract: High-level production of β-globin, γ-globin, or therapeutic mutant globins in the RBC lineage by hematopoietic stem cell gene therapy ameliorates or cures the hemoglobinopathies sickle cell disease and beta thalassemia, which are major causes of morbidity and mortality worldwide. Considerable efforts have been made in the last 2 decades in devising suitable gene-transfer vectors and protocols to achieve this goal. Five years ago, the first β(E)/β(0)-thalassemia major (transfusion-dependent) patient was treated by globin lentiviral gene therapy without injection of backup cells. This patient has become completely transfusion independent for the past 4 years and has global amelioration of the thalassemic phenotype. Partial clonal dominance for an intragenic site (HMGA2) of chromosomal integration of the vector was observed in this patient without a loss of hematopoietic homeostasis. Other patients are now receiving transplantations while researchers are carefully weighing the benefit/risk ratio and continuing the development of further modified vectors and protocols to improve outcomes further with respect to safety and efficacy.
authors.affiliation: Commissariat a l'Energie Atomique, Institute of Emerging Diseases and Innovative Therapies, Fontenay aux Roses, France. leboulch@rics.bwh.harvard.edu
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Payen
authors.forename: Philippe
authors.initials: P
authors.lastname: Leboulch
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics / Q000628:therapy; D018952:Antigens, CD34 / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D002986:Clinical Trials as Topic; D005319:Fetal Hemoglobin / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006453:Hemoglobinopathies / Q000235:genetics* / Q000628:therapy*; D006706:Homeostasis; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008957:Models, Genetic; D016296:Mutagenesis; D009154:Mutation; D010641:Phenotype; D035781:Siblings; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome; D017086:beta-Thalassemia / Q000235:genetics / Q000628:therapy
chemical_list: D018952:Antigens, CD34; D005319:Fetal Hemoglobin