{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:20:50Z","timestamp":1784647250622,"version":"3.55.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chimeric Antigen Receptor T cell(CAR T-cell) therapy has been a great success in relapsed\/refractory acute B lymphoblastic leukemia and B-cell lymphoma. At the same time, there are also related adverse reactions, especially cytokine release syndrome(CRS) and immune effector cell associated neurotoxicity syndrome(ICANS). However, Double CRS caused by CRA T cells are very rare.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case report<\/jats:title><jats:p>Here, we report a 33-year-male with secondary central diffuse large B-cell lymphoma(CNSL) who develpoed double CRS following sequential infusion of Anti-CD22 and Anti-CD19 CAR T cells after autologous hematopoietic stem cell transplantation(ASCT). On d+5, the patient developed high fever, along with chilly sensation, shivering, headache, blood oxygen desaturation, shock, weakness, severe thirst, and heart rate decline. IL-6 and ferritin increased significantly. The patient was diagnosed with the first CRS (grade 3). On d+36, the patient again had a persistent fever(T&amp;gt;39C) and limbs rash. IL-6 and ferritin again increased significantly on d+38. After exclusion of infection, a diagnosis of double CRS was made. The patient\u2019s symptoms were completely relieved after receiving tocilizumab, glucocorticoids, and other supportive treatments on d+45.On d+90, contrast-enhanced MR angiogram shows that the lesion basically disappeared, indicating the patient had achieved CR. At the end of the follow-up at d+150, the patient was functioning normally without any sequelae.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first reported case worldwide where the patient with secondary CNSL suffered double CRS after CAR T-cell infusion. Our findings showed that it is important to increase awareness of early detection and diagnosis of double CRS and adopt appropriate treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1098815","type":"journal-article","created":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T04:50:35Z","timestamp":1675140635000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Double systemic cytokine release syndrome following sequential infusion of anti-CD22 and anti-CD19 chimeric antigen receptor T cells after autologous hematopoietic stem cell transplantation for a central diffuse large B-cell lymphoma patient: A case report and literature review"],"prefix":"10.3389","volume":"14","author":[{"given":"Jing","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue Q.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong Z.","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai B.","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s13045-018-0593-5","article-title":"CD19 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