title: Failure of SCID-X1 gene therapy in older patients.
abstract: Gene therapy has been shown to be a highly effective treatment for infants with typical X-linked severe combined immunodeficiency (SCID-X1, gammac-deficiency). For patients in whom previous allogeneic transplantation has failed, and others with attenuated disease who may present later in life, the optimal treatment strategy in the absence of human leukocyte antigen (HLA)-matched donors is unclear. Here we report the failure of gene therapy in 2 such patients, despite effective gene transfer to bone marrow CD34(+) cells, suggesting that there are intrinsic host-dependent restrictions to efficacy. In particular, there is likely to be a limitation to initiation of normal thymopoiesis, and we therefore suggest that intervention for these patients should be considered as early as possible.
authors.affiliation: Molecular Immunology Unit, Institute of Child Health, London, United Kingdom.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: Salima
authors.initials: S
authors.lastname: Hacein-Bey-Abina
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.forename: Stephane
authors.initials: S
authors.lastname: Blanche
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
authors.forename: Kathryn
authors.initials: K
authors.lastname: Parsley
authors.forename: Kimberly
authors.initials: K
authors.lastname: Gilmour
authors.forename: Douglas
authors.initials: D
authors.lastname: King
authors.forename: Steven
authors.initials: S
authors.lastname: Howe
authors.forename: Joanna
authors.initials: J
authors.lastname: Sinclair
authors.forename: Christophe
authors.initials: C
authors.lastname: Hue
authors.forename: Frédérique
authors.initials: F
authors.lastname: Carlier
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Geneviève
authors.initials: G
authors.lastname: de Saint Basile
authors.forename: Françoise
authors.initials: F
authors.lastname: le Deist
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
mesh_terms: D000328:Adult; D018952:Antigens, CD34; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D040181:Genetic Diseases, X-Linked / Q000628:therapy*; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D014161:Transduction, Genetic; D017211:Treatment Failure
chemical_list: D018952:Antigens, CD34