title: Bone marrow as a source of hematopoietic stem cells for human gene therapy of β-thalassemia.
abstract: β-Thalassemia is a severe inherited anemia caused by insufficient production of β-globin chains. Allogeneic hematopoietic stem cell (HSC) transplantation is currently the only cure, and is limited by donor availability and regimen-related toxicity and mortality. Gene therapy is a promising therapeutic tool for all thalassemic patients lacking a compatible donor and potentially provides transfusion independence in the absence of transplant-related complications, such as graft rejection and graft-versus-host disease. The issue of HSC procurement is critical in this setting because of the specific features of thalassemic syndromes, which include bone marrow (BM) expansion, ineffective erythropoiesis, and splenomegaly. Little is known about the efficiency of CD34(+) cell yield from steady-state BM harvests from thalassemic patients. We have collected data on safety and cell yield from 20 pediatric patients with β-thalassemia who underwent autologous BM harvest before allogeneic HSC transplantation, and from 49 age-matched sibling donors who also underwent BM harvest. The procedure was safe, as no significant adverse events occurred. In terms of cell yield, no difference was found between patients and normal donors in the number of CD34(+) cells and total nucleated cells harvested. Most importantly, no difference was found in the proportion of myeloid and erythroid progenitors, suggesting a similar repopulating capacity. On the basis of these results, we conclude that steady-state BM can be used as a safe and efficient source of HSC for gene therapy of β-thalassemia.
authors.affiliation: Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Marta Claudia
authors.initials: MC
authors.lastname: Frittoli
authors.forename: Erika
authors.initials: E
authors.lastname: Biral
authors.forename: Barbara
authors.initials: B
authors.lastname: Cappelli
authors.forename: Matilde
authors.initials: M
authors.lastname: Zambelli
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Roncarolo
authors.forename: Giuliana
authors.initials: G
authors.lastname: Ferrari
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Sarah
authors.initials: S
authors.lastname: Marktel
mesh_terms: D000293:Adolescent; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D014182:Transplantation, Autologous; D017086:beta-Thalassemia / Q000628:therapy*
chemical_list: D018952:Antigens, CD34; D017493:Leukocyte Common Antigens