title: Role of reduced intensity conditioning in T-cell and B-cell immune reconstitution after HLA-identical bone marrow transplantation in ADA-SCID.
abstract: The treatment of choice for severe combined immunodeficiency is bone marrow transplantation from an HLA-identical donor sibling without conditioning. However, this may result in low donor stem cell chimerism, leading to reduced long-term immune reconstitution. We compared engraftment, metabolic, and T-cell and B-cell immune reconstitution of HLA-identical sibling bone marrow transplantation performed in 2 severe combined immunodeficiency infants with adenosine deaminase deficiency from the same family treated with or without a reduced intensity conditioning regimen (busulfan/fludarabine). Only the patient who received conditioning showed a stable mixed chimerism in all lineages, including bone marrow myeloid and B cells. The use of conditioning resulted in higher thymus-derived naïve T cells and T-cell receptor excision circles, normalization of the T-cell repertoire, and faster and complete B-cell and metabolic reconstitution. These results suggest the utility of exploring the use of reduced intensity conditioning in bone marrow transplantation from HLA-identical donor in severe combined immunodeficiency to improve long-term immune reconstitution.
authors.affiliation: HSR-TIGET, Istituto Scientifico HS Raffaele, via Olgettina 58, Milan, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cancrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrua
authors.forename: Alessia
authors.initials: A
authors.lastname: Scarselli
authors.forename: Immacolata
authors.initials: I
authors.lastname: Brigida
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Romiti
authors.forename: Graziano
authors.initials: G
authors.lastname: Barera
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Roncarolo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Caniglia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency; D000361:Agammaglobulinemia / Q000628:therapy; D001402:B-Lymphocytes / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods*; D006085:Graft Survival; D006801:Humans; D007223:Infant; D016511:Severe Combined Immunodeficiency / Q000628:therapy*; D035781:Siblings; D013601:T-Lymphocytes / Q000166:cytology; D019172:Transplantation Conditioning / Q000379:methods*; D014185:Transplantation, Isogeneic
chemical_list: D000243:Adenosine Deaminase
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