{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T02:39:01Z","timestamp":1775615941198,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>CAR<jats:sup>\u2212<\/jats:sup> CD4<jats:sup>+<\/jats:sup> T cell lymphopenia is an emerging issue following CAR\u2010T cell therapy. We analyzed the determinants of CD4<jats:sup>+<\/jats:sup> T cell recovery and a possible association with survival in 31 consecutive patients treated with commercial CAR\u2010T for diffuse large B\u2010cell (DLBCL) or mantle cell lymphoma. Circulating immune subpopulations were characterized through multiparametric\u2010flow cytometry. Six\u2010month cumulative incidence of CAR<jats:sup>\u2212<\/jats:sup> CD4<jats:sup>+<\/jats:sup> T cell recovery (\u2265200 cells\/\u03bcL) was 0.43 (95% confidence interval [CI]: 0.28\u20130.65). Among possible determinants of CD4<jats:sup>+<\/jats:sup> T cell recovery, we recognized infusion of a 4\u20101BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene\/brexucabtagene, AXI\/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16\u201324.12] <jats:italic>p<\/jats:italic>\u00a0=\u00a00.016). Higher CD4<jats:sup>+<\/jats:sup> T cell counts resulted with TSA at month\u20101, \u20102 and \u20103. Moderate\u2010to\u2010severe infections were registered with prolonged CD4<jats:sup>+<\/jats:sup> T cell lymphopenia. Early, month\u20101 CD4<jats:sup>+<\/jats:sup> T cell recovery was associated with a worse outcome in the DLBCL cohort, upheld in a multivariate regression model for overall survival (HR: 4.46 [95% CI: 1.12\u201317.71], <jats:italic>p<\/jats:italic>\u00a0=\u00a00.03). We conclude that a faster CAR<jats:sup>\u2212<\/jats:sup> CD4<jats:sup>+<\/jats:sup> T cell recovery is associated with TSA as compared to AXI\/BRX. Month\u20101 CAR<jats:sup>\u2212<\/jats:sup> CD4<jats:sup>+<\/jats:sup> T cell subset recovery could represent a \u201cred flag\u201d for CAR\u2010T cell therapy failure in DLBCL patients.<\/jats:p>","DOI":"10.1002\/jha2.871","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:38:21Z","timestamp":1710290301000},"page":"360-368","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Early CAR<sup>\u2212<\/sup> CD4<sup>+<\/sup> T\u2010lymphocytes recovery following CAR\u2010T cell infusion: A worse outcome in diffuse large B cell lymphoma"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7896-4198","authenticated-orcid":false,"given":"Massimiliano","family":"Gambella","sequence":"first","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"},{"name":"Department of Experimental Medicine (DIMES) University of Genoa Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Carlomagno","sequence":"additional","affiliation":[{"name":"Department of Medicine (DMED) University of Udine  Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Mangerini","sequence":"additional","affiliation":[{"name":"Anatomia Patologica Ospedaliera IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Colombo","sequence":"additional","affiliation":[{"name":"Anatomia Patologica Ospedaliera IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Parodi","sequence":"additional","affiliation":[{"name":"Anatomia Patologica Ospedaliera IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Ghiggi","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Giannoni","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Coviello","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Setti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES) University of Genoa Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Luchetti","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Serio","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Laudisi","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Passannante","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Bo","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Tedone","sequence":"additional","affiliation":[{"name":"Anatomia Patologica Ospedaliera IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Sivori","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES) University of Genoa Genova Italy"},{"name":"IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Angelucci","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Raiola","sequence":"additional","affiliation":[{"name":"Ematologia e Terapie Cellulari IRCCS Ospedale Policlinico San Martino Genova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.13375"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.254045"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002732"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.238634"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1061-7"},{"issue":"26","key":"e_1_2_13_7_1","first-page":"3153","article-title":"Costimulatory domains direct distinct fates of CAR\u2010driven T cell dysfunction","volume":"141","author":"Selli ME","year":"2023","journal-title":"Blood"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01959-0"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01960-7"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.12.758"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.229781"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.8800"},{"key":"e_1_2_13_13_1","first-page":"349","article-title":"GLA\/DRST real\u2010world outcome analysis of CAR\u2010T cell therapies for large B\u2010cell lymphoma in Germany","volume":"140","author":"Bethge WA","year":"2022","journal-title":"Blood"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407222"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000836"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003005"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2021.07.023"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.796349"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2022.07.011"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2021.39.15_suppl.7552"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01969-y"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022008240"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124218"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13016"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5971-z"}],"container-title":["eJHaem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.871","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T10:18:41Z","timestamp":1713262721000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jha2.871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,12]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/jha2.871"],"URL":"https:\/\/doi.org\/10.1002\/jha2.871","archive":["Portico"],"relation":{},"ISSN":["2688-6146","2688-6146"],"issn-type":[{"value":"2688-6146","type":"print"},{"value":"2688-6146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,12]]},"assertion":[{"value":"2024-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}