{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:17:16Z","timestamp":1787919436541,"version":"build-2784847793"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Uniwersytet Medyczny im. Piast\u00f3w Slaskich we Wroclawiu","doi-asserted-by":"publisher","award":["SUBZ.C200.26.031"],"award-info":[{"award-number":["SUBZ.C200.26.031"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023181","name":"Agencja Bada\u0144 Medycznych","doi-asserted-by":"publisher","award":["2020\/ABM\/01\/00107, 2020\/ABM\/01\/00125"],"award-info":[{"award-number":["2020\/ABM\/01\/00107, 2020\/ABM\/01\/00125"]}],"id":[{"id":"10.13039\/501100023181","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n Cellular immunotherapies\u2014including chimeric antigen receptor T-cell (CAR-T) therapies and adoptive transfer of virus-specific T lymphocytes (VSTs) \u2014 have transformed the treatment of refractory hematological malignancies and post-transplant infectious complications. Eight products are currently authorized by the European Medicines Agency, encompassing seven autologous CAR-T products targeting CD19 or BCMA and tabelecleucel (Ebvallo), the first approved allogeneic off-the-shelf EBV-specific T-cell product for EBV-positive post-transplant lymphoproliferative disease. Despite their clinical efficacy, both modalities carry distinct early toxicity profiles that differ from conventional cytotoxic chemotherapy.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n This review summarizes current recommendations for identifying, assessing, and treating early problems that can occur after CAR-T cell therapy and VST administration.<\/jats:p>\n <\/jats:sec>\n \n Content<\/jats:title>\n CAR-T-specific complications discussed include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), and immune effector cell-associated HLH-like syndrome (IEC-HS). CRS is graded by ASTCT consensus criteria and managed with tocilizumab as first-line pharmacological therapy; steroid-refractory ICANS is most commonly treated with high-dose intravenous anakinra (up to 12 mg\/kg\/day) which is currently the most studied second-line option, although the supporting evidence remains largely observational. ICAHT is classified using the validated EHA\/EBMT grading framework, separating early (day 0\u201330) and late (post-day 30) neutropenia by depth and duration, with management escalating from prophylactic G-CSF through hematopoietic cell boost to allogeneic HSCT as the ultimate option. For VSTs, the principal early complications are tumor flare reaction (in approximately 20% of tabelecleucel recipients), GVHD (below 5% with enriched products), acute infusion reactions, and low-grade CRS-like cytokine release. We summarize a differential diagnosis of overlapping syndromes, pediatric-specific adaptations, ICU escalation criteria, and a clinical monitoring schedule.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Internationally validated criteria grade the early complications of cellular immune effector therapies. Prompt recognition, early pharmacological intervention, and monitoring are essential to minimize non-relapse mortality. Expanding real-world experience and the integration of pre-treatment risk stratification tools will continue to refine evidence-based practice in this rapidly evolving field, ultimately leading to improved patient outcomes and reduced non-relapse mortality rates.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1884854","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T11:40:55Z","timestamp":1787917255000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Recognition and management of early complications in CAR-T cell therapy and virus-specific T-lymphocyte therapy: a practical clinical reference"],"prefix":"10.3389","volume":"17","author":[{"given":"Marek","family":"Ussowicz","sequence":"first","affiliation":[{"name":"Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University","place":["Wroc\u0142aw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Jakubczyk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, University Clinical Hospital","place":["Wroc\u0142aw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Department and Clinic of Hematology, Cellular Therapies, and Internal Medicine, Wroclaw Medical University","place":["Wroc\u0142aw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Czy\u017c","sequence":"additional","affiliation":[{"name":"Department and Clinic of Hematology, Cellular Therapies, and Internal Medicine, Wroclaw Medical University","place":["Wroc\u0142aw, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000540961","article-title":"Virus-specific T-cell therapy for the management of viral infections in the immunocompromised","volume":"2024","author":"Koukoulias","year":"2024","journal-title":"Transfusion Med Hemotherapy"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-12-063008","article-title":"Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial","volume":"110","author":"Haque","year":"2007","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.5.1549","article-title":"Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients","volume":"92","author":"Rooney","year":"1998","journal-title":"Blood"},{"key":"B4","unstructured":"Ebvallo: EPAR - Product Information. 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