title: Faster T-cell development following gene therapy compared with haploidentical HSCT in the treatment of SCID-X1.
abstract: During the last decade, gene therapy via ex vivo gene transfer into autologous hematopoietic stem cells has emerged as a convincing therapy for severe combined immunodeficiency caused by ILR2G mutation (SCID-X1) despite the occurrence of genotoxicity caused by the integration of first-generation retroviral vectors. However, the place of gene therapy among the therapeutic armamentarium remains to be defined. We retrospectively analyze and compare clinical outcomes and immune reconstitution in 13 consecutive SCID-X1 patients having undergone haploidentical hematopoietic stem cell transplantation (HSCT) and 14 SCID-X1 patients treated with gene therapy over the same period at a single center level: the Necker Children's Hospital (Paris, France). Our results show a clear advantage in terms of T-cell development of gene therapy over HSCT with a mismatched donor. Patients treated with gene therapy display a faster T-cell reconstitution and a better long-term thymic output. Interestingly, this advantage of gene therapy vs haploidentical HSCT seems to be independent of the existence of clinical graft-versus-host disease in the latter condition. If data of safety are confirmed over the long term, gene therapy for SCID-X1 appears to be an equal, if not superior, alternative to haploidentical HSCT.
authors: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France;
authors: Fabien
authors: F
authors: Touzot
authors: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors: Despina
authors: D
authors: Moshous
authors: Laboratoire de Biochimie, Centre Hospitalier Intercommunal de Creteil, Paris, France;
authors: Rita
authors: R
authors: Creidy
authors: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors: Bénédicte
authors: B
authors: Neven
authors: Laboratoire de Microbiologie, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; EA 3620, Université Paris Descartes-Sorbonne Paris Cité, Paris, France;
authors: Pierre
authors: P
authors: Frange
authors: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France;
authors: Guilhem
authors: G
authors: Cros
authors: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors: Laure
authors: L
authors: Caccavelli
authors: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors: Johanna
authors: J
authors: Blondeau
authors: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France;
authors: Alessandra
authors: A
authors: Magnani
authors: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors: Jean-Marc
authors: JM
authors: Luby
authors: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors: Brigitte
authors: B
authors: Ternaux
authors: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Centre d'étude des Déficits Immunitaires, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France;
authors: Capucine
authors: C
authors: Picard
authors: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France;
authors: Stéphane
authors: S
authors: Blanche
authors: Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; College de France, Paris, France; and.
authors: Alain
authors: A
authors: Fischer
authors: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Paris, France; Laboratoire d'Immunologie, Groupe Hospitalier-Universitaire Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France.
authors: Salima
authors: S
authors: Hacein-Bey-Abina
authors: Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France;
authors: Marina
authors: M
authors: Cavazzana
mesh_terms: D000293:Adolescent; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D005260:Female; D015316:Genetic Therapy; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000276:immunology*; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology; D053632:X-Linked Combined Immunodeficiency Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit