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dc.contributor.authorKohn, Donald B.
dc.contributor.authorNewburger, Peter E.
dc.contributor.authorBooth, Claire
dc.contributor.authorKang, Elizabeth M.
dc.contributor.authorPai, Sung-Yun
dc.contributor.authorShaw, Kit L.
dc.contributor.authorSantilli, Giorgia
dc.contributor.authorArmant, Myriam
dc.contributor.authorBuckland, Karen F.
dc.contributor.authorChoi, Uimook
dc.contributor.authorDe Ravin, Suk See.
dc.contributor.authorDorsey, Morna J.
dc.contributor.authorLeon-Rico, Diego
dc.contributor.authorRivat, Christine
dc.date2022-08-11T08:10:13.000
dc.date.accessioned2022-08-23T16:59:59Z
dc.date.available2022-08-23T16:59:59Z
dc.date.issued2020-02-01
dc.date.submitted2020-03-10
dc.identifier.citation<p>Nat Med. 2020 Feb;26(2):200-206. doi: 10.1038/s41591-019-0735-5. Epub 2020 Jan27. <a href="https://doi.org/10.1038/s41591-019-0735-5">Link to article on publisher's site</a></p>
dc.identifier.issn1078-8956 (Linking)
dc.identifier.doi10.1038/s41591-019-0735-5
dc.identifier.pmid31988463
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43709
dc.description<p>Full list of authors omitted for brevity. For full list see article.</p>
dc.description.abstractChronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells(1,2). We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34(+) hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4-1.8 copies per neutrophil) and the persistence of 16-46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31988463&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1038/s41591-019-0735-5
dc.subjectCongenital, Hereditary, and Neonatal Diseases and Abnormalities
dc.subjectHematology
dc.subjectHemic and Lymphatic Diseases
dc.subjectPediatrics
dc.titleLentiviral gene therapy for X-linked chronic granulomatous disease
dc.typeJournal Article
dc.source.journaltitleNature medicine
dc.source.volume26
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/peds_pp/295
dc.identifier.contextkey16756921
html.description.abstract<p>Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells(1,2). We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34(+) hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685). The primary objectives were to assess the safety and evaluate the efficacy and stability of biochemical and functional reconstitution in the progeny of engrafted cells at 12 months. The secondary objectives included the evaluation of augmented immunity against bacterial and fungal infection, as well as assessment of hematopoietic stem cell transduction and engraftment. Two enrolled patients died within 3 months of treatment from pre-existing comorbidities. At 12 months, six of the seven surviving patients demonstrated stable vector copy numbers (0.4-1.8 copies per neutrophil) and the persistence of 16-46% oxidase-positive neutrophils. There was no molecular evidence of either clonal dysregulation or transgene silencing. Surviving patients have had no new CGD-related infections, and six have been able to discontinue CGD-related antibiotic prophylaxis. The primary objective was met in six of the nine patients at 12 months follow-up, suggesting that autologous gene therapy is a promising approach for CGD patients.</p>
dc.identifier.submissionpathpeds_pp/295
dc.contributor.departmentDepartment of Pediatrics
dc.source.pages200-206


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