{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:56:46Z","timestamp":1789016206387,"version":"build-2803163510"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Autologous CD19-directed chimeric antigen receptor (CAR)-T cells have shown unprecedented efficacy in children with relapsed\/refractory B-cell-precursor acute lymphoblastic leukemia (BCP-ALL). However, patients either relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT), or displaying profound lymphopenia and\/or with rapidly progressing disease often cannot access autologous products. These hurdles may be overcome by allogeneic, donor-derived CAR-T cells. We tested donor-derived T-cells transduced with a 2nd-generation (4.1BB) CD19-CAR for treatment of patients with BCP-ALL, in a hospital exemption setting. Two constructs were tested: a retroviral construct incorporating the suicide gene inducible caspase-9 (CD19-CAR-Retro_ALLO) first and then a lentiviral construct and an automated, Prodigy\u00ae-based, manufacturing process (CD19-CAR-Lenti_ALLO). Thirteen children\/young adults received ALLO-CAR T-cells between 03\/2021 and 10\/2022. Doses ranged between 1,0\u00d7106 and 3,0\u00d7106 CAR T-cells\/kg. The toxicity profile was comparable to that of autologous CAR-T cells, characterized mainly by cytopenia, CRS (maximum grade 1) and grade 2 ICANS. One case of acute graft-versus-host disease (GvHD) occurred and was rapidly controlled by steroids and ruxolitinib. None of the other patients, including 3 infused with ALLO-CAR T cells from an HLA-haplo-identical donor, experienced GvHD. Two patients received ALLO-CAR T-cells before HSCT and showed a significant expansion of CAR T cells, without any sign of GvHD. All patients obtained complete remission (CR) with negativity of minimal residual disease in the BM; with a median follow-up of 12 months (range 5-21), 8\/13 patients maintain CR. Allogeneic anti-CD19 CAR-T cells can effectively treat highly-refractory BCP-ALL relapsing after alloHSCT, without showing increased toxicity as compared to autologous CAR T cells.<\/jats:p>","DOI":"10.1182\/blood.2023020023","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T15:04:04Z","timestamp":1683903844000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["Allogeneic, donor-derived, second-generation, CD19-CAR-T cell for the treatment of pediatric relapsed\/refractory BCP-ALL"],"prefix":"10.1182","author":[{"given":"Francesca","family":"del Bufalo","sequence":"first","affiliation":[{"name":"IRCCS Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-4092","authenticated-orcid":false,"given":"Marco","family":"Becilli","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Rosignoli","sequence":"additional","affiliation":[{"name":"IRCCS Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-737X","authenticated-orcid":false,"given":"Biagio","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Algeri","sequence":"additional","affiliation":[{"name":"IRCCS Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Hanssens","sequence":"additional","affiliation":[{"name":"Miltenyi Biomedicine, Germany, Bergisch Gladbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7466-4972","authenticated-orcid":false,"given":"Monica","family":"Gunetti","sequence":"additional","affiliation":[{"name":"IRCCS Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0806-6365","authenticated-orcid":false,"given":"Stefano","family":"Iacovelli","sequence":"additional","affiliation":[{"name":"IRCCS Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Li Pira","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elia","family":"Girolami","sequence":"additional","affiliation":[{"name":"IRCCS Bambino Ges\u00f9 Children's Hospital, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Dr","given":"Giovanna","family":"Leone","sequence":"additional","affiliation":[{"name":"IRCCS Bambino Ges\u00f9 Children Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Lazzaro","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9028-7767","authenticated-orcid":false,"given":"Valentina","family":"Bertaina","sequence":"additional","affiliation":[{"name":"Ospedale Pediatrico Bambino Ges\u00f9 Roma, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Sinibaldi","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2595-9261","authenticated-orcid":false,"given":"Stefano","family":"Di Cecca","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Iaffaldano","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8406-5412","authenticated-orcid":false,"given":"Annette","family":"K\u00fcnkele","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Boccieri","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3540-4331","authenticated-orcid":false,"given":"Giada","family":"Del Baldo","sequence":"additional","affiliation":[{"name":"IRCCS Bambino Ges\u00f9 Children's Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Pagliara","sequence":"additional","affiliation":[{"name":"IRCCS Bambino Gesu Children's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6426-4046","authenticated-orcid":false,"given":"Pietro","family":"Merli","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Carta","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4343-9705","authenticated-orcid":false,"given":"Concetta","family":"Quintarelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples Federico II, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Bambino Ges\u00f9 Children's Hospital, Catholic University of Sacred Heart, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2023,5,12]]},"container-title":["Blood Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2023020023\/2051020\/blood.2023020023.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2023020023\/2051020\/blood.2023020023.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T15:04:08Z","timestamp":1683903848000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2023020023\/495807\/Allogeneic-donor-derived-second-generation-CD19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,12]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2023020023","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742642345.793598746","asserted-by":"object"}]},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,12]]},"article-number":"blood.2023020023"}}