dc.contributor.author | Cicalese, Maria Pia | |
dc.contributor.author | Ferrua, Francesca | |
dc.contributor.author | Castagnaro, Laura | |
dc.contributor.author | Pajno, Roberta | |
dc.contributor.author | Barzaghi, Federica | |
dc.contributor.author | Giannelli, Stefania | |
dc.contributor.author | Dionisio, Francesca | |
dc.contributor.author | Brigida, Immacolata | |
dc.contributor.author | Bonopane, Marco | |
dc.contributor.author | Casiraghi, Miriam | |
dc.contributor.author | Tabucchi, Antonella | |
dc.contributor.author | Carlucci, Filippo | |
dc.contributor.author | Grunebaum, Eyal | |
dc.contributor.author | Adeli, Mehdi | |
dc.contributor.author | Bredius, Robbert G. | |
dc.contributor.author | Puck, Jennifer M. | |
dc.contributor.author | Stepensky, Polina | |
dc.contributor.author | Tezcan, Ilhan | |
dc.contributor.author | Rolfe, Katie | |
dc.contributor.author | De Boever, Erika | |
dc.contributor.author | Reinhardt, Rickey R. | |
dc.contributor.author | Appleby, Jonathan | |
dc.contributor.author | Ciceri, Fabio | |
dc.contributor.author | Roncarolo, Maria Grazia | |
dc.contributor.author | Aiuti, Alessandro | |
dc.date.accessioned | 2019-12-10T11:21:06Z | |
dc.date.available | 2019-12-10T11:21:06Z | |
dc.date.issued | 2016 | |
dc.identifier.issn | 0006-4971 | |
dc.identifier.uri | https://doi.org/10.1182/blood-2016-01-688226 | |
dc.identifier.uri | http://hdl.handle.net/11655/15434 | |
dc.description.abstract | Adenosine deaminase (ADA) deficiency is a rare, autosomal-recessive systemic metabolic disease characterized by severe combined immunodeficiency (SCID). The treatment of choice for ADA-deficient SCID (ADA-SCID) is hematopoietic stem cell transplant from an HLA-matched sibling donor, although <25% of patients have such a donor available. Enzyme replacement therapy (ERT) partially and temporarily relieves immunodeficiency. We investigated the medium-term outcome of gene therapy (GT) in 18 patients with ADA-SCID for whom an HLA-identical family donor was not available; most were not responding well to ERT. Patients were treated with an autologous CD34(+)-enriched cell fraction that contained CD34 1 cells transduced with a retroviral vector encoding the human ADA complementary DNA sequence (GSK2696273) as part of single-arm, open-label studies or compassionate use programs. Overall survival was 100% over 2.3 to 13.4 years (median, 6.9 years). Gene-modified cells were stably present inmultiple lineages throughout follow up. GT resulted in a sustained reduction in the severe infection rate from 1.17 events per person-year to 0.17 events per person-year (n = 17, patient 1 data not available). Immune reconstitution was demonstrated by normalization of T-cell subsets (CD3(+), CD4(+), and CD8(+)), evidence of thymopoiesis, and sustained T-cell proliferative capacity. B-cell function was evidenced by immunoglobulin production, decreased intravenous immunoglobulin use, and antibody response after vaccination. All 18 patients reported infections as adverse events; infections of respiratory and gastrointestinal tracts were reported most frequently. No events indicative of leukemic transformation were reported. Trial details were registered at www.clinicaltrials.gov as #NCT00598481. | |
dc.language.iso | en | |
dc.publisher | Amer Soc Hematology | |
dc.relation.isversionof | 10.1182/blood-2016-01-688226 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | Hematology | |
dc.title | Update On The Safety And Efficacy Of Retroviral Gene Therapy For Immunodeficiency Due To Adenosine Deaminase Deficiency | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:eu-repo/semantics/publishedVersion | |
dc.relation.journal | Blood | |
dc.contributor.department | İç Hastalıkları | |
dc.identifier.volume | 128 | |
dc.identifier.issue | 1 | |
dc.identifier.startpage | 45 | |
dc.identifier.endpage | 54 | |
dc.description.index | WoS | |
dc.description.index | Scopus | |