{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:36:31Z","timestamp":1791246991576,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is successful in pediatric patients with inborn errors of immunity (IEI), but its use in adults is complicated by pre-existing organ damage and increased risk of treatment-related mortality.\n                      <jats:italic>Ex vivo<\/jats:italic>\n                      graft engineering using \u03b1\u03b2TCR\/CD19 depletion has shown promising safety profiles in pediatric IEI, yet evidence in adults is limited. We assessed the feasibility and outcomes of \u03b1\u03b2TCR\/CD19-depleted allo-HSCT in adults with IEI, focusing on engraftment, immune reconstitution, and clinical outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 9 adults with IEI and 1 with VEXAS (age 21\u201351). IEIs included CTLA4HI, APDS, DOCK8, ALPS, DADA2, CVID2, and HA20, with Immune Deficiency and Dysregulation Activity (IDDA) scores of 17\u201392. \u03b1\u03b2TCR\/CD19-depleted allografts from related, unrelated or haplo-identical donors were used after antithymocyte globulin (ATG) and myeloablative conditioning (thiotepa, melphalan, and fludarabine). Post-transplant immunoprophylaxis included mycophenolate mofetil; 4\/10 patients received additional transplant-associated immunosuppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All patients achieved primary engraftment. One patient with secondary rejection successfully underwent a second allo-HSCT. 5 patients developed grade 2\u20134 acute GvHD; no chronic GvHD was observed. One patient with GvHD died from COVID-19. All remaining 9 patients were successfully tapered off immunosuppression and showed improved IDDA scores. At 6 months NK, \u03b3\u03b4T, B and CD8\u2009+\u2009T cells normalized; CD4\u2009+\u2009numbers reached 149 cells\/\u00b5l at 1 year. Most patients were successfully vaccinated and could stop immunoglobulin substitution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In conclusion,\n                      <jats:italic>ex vivo<\/jats:italic>\n                      graft engineering using \u03b1\u03b2TCR\/CD19 depletion was feasible in adults with IEI. Clinical outcomes are encouraging, but need to be confirmed in larger studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10875-025-01978-9","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T19:35:00Z","timestamp":1770147300000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["\u03b1\u03b2T\/CD19-depleted Allogeneic Stem Cell Transplantation in Adults with Inborn Errors of Immunity"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7901-7510","authenticated-orcid":false,"given":"Janneke J. H.","family":"de Winter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birtan M.","family":"Ibrahimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances A.","family":"Verheij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris D.","family":"Brinkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0797-4050","authenticated-orcid":false,"given":"Anniek H. G.","family":"Stuut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5017-8415","authenticated-orcid":false,"given":"Pleun","family":"Schonewille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1718-7855","authenticated-orcid":false,"given":"Marloes W.","family":"Heijstek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"van Rhenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte E.","family":"van der Wagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9835-3223","authenticated-orcid":false,"given":"Laura G. M.","family":"Daenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5353-1740","authenticated-orcid":false,"given":"Tim J. A.","family":"Hutten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3914-7806","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Kuball","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8720-3684","authenticated-orcid":false,"given":"Helen L.","family":"Leavis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-2994","authenticated-orcid":false,"given":"Moniek A.","family":"de Witte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"issue":"7","key":"1978_CR1","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1586\/1744666X.2016.1150177","volume":"12","author":"C Booth","year":"2016","unstructured":"Booth C, Silva J, Veys P. Stem cell transplantation for the treatment of immunodeficiency in children: current status and hopes for the future. Expert Rev Clin Immunol. 2016;12(7):713\u201323.","journal-title":"Expert Rev Clin Immunol"},{"issue":"1","key":"1978_CR2","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.jaci.2021.04.036","volume":"149","author":"D Dimitrova","year":"2022","unstructured":"Dimitrova D, Nademi Z, Maccari ME, Ehl S, Uzel G, Tomoda T, et al. International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome. J Allergy Clin Immunol. 2022;149(1):410-21 e7.","journal-title":"J Allergy Clin Immunol"},{"issue":"5","key":"1978_CR3","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1016\/j.jaci.2021.10.017","volume":"149","author":"AC Lankester","year":"2022","unstructured":"Lankester AC, Neven B, Mahlaoui N, von Asmuth EGJ, Courteille V, Alligon M, et al. 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Blood. 2023;141(1):60\u201371.","journal-title":"Blood"}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-025-01978-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-025-01978-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-025-01978-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:10:32Z","timestamp":1771305032000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-025-01978-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1978"],"URL":"https:\/\/doi.org\/10.1007\/s10875-025-01978-9","relation":{},"ISSN":["1573-2592"],"issn-type":[{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"assertion":[{"value":"15 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients provided written informed consent indicating their agreement to participate in the Dutch National \u2018IEI\u2019 registry and gave consent for sending their data to EBMT. The informed consent form was approved by the local ethical committee (METC NL40331.078 & METC nr 21\u2013322) at the UMCU. The study adhered to Good Clinical Practice (GCP) protocols and the principles outlined in the Declaration of Helsinki. Clinical trial number: not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval\/Consent to Participate"}},{"value":"JK is inventor on multiple patents dealing with gammadelta-TCRs, ligands, and isolation strategies of engineered immune cells. JK is cofounder and shareholder of Gadeta. JK received research, advisor and clinical study support from Miltenyi Biotec. JK received further research support from Novartis and Gadeta. HL received research support from Takeda, Novartis and Sobi. HL received advisor, presentation and moderating fees from Takeda, Novartis, Sobi and Octapharma. MdW received grant support from Leukemiefonds.nl and Oncode Accelerator. MdW received research support from Miltenyi Biotec and Novartis. MdW received speakers fee from AbbVie, GSK, Miltenyi Biotec, Novartis and Takeda. The rest of the authors declare no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"21"}}