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High-grade CRS is serious and may require intensive care, yet reliable early predictive markers remain elusive. To identify risk factors for high-grade CRS, we retrospectively analyzed B-cell lymphoma patients who received CD19 CAR-T cell therapy. Of 106 patients analyzed, CRS occurred in 93 (88%), Grade\u2009\u2265\u20092 CRS in 28 (26%), and Grade\u2009\u2265\u20093 CRS in 6 (6%). Reticulocyte counts at infusion were significantly lower in patients who developed Grade\u2009\u2265\u20092 CRS (1.85 vs. 2.80\u2009\u00d7\u200910\n                    <jats:sup>4<\/jats:sup>\n                    \/\u00b5L, p\u2009=\u20090.02). Multivariate analysis identified low reticulocyte count (&lt;\u200915,000\/\u00b5L; HR 2.21; 95% CI 1.01\u20134.86; p\u2009=\u20090.048), high metabolic tumor volume (&gt;\u2009100\u00a0mL), and use of axicabtagene ciloleucel as independent risk factors for Grade\u2009\u2265\u20092 CRS. Stratification by the reticulocyte cutoff showed higher 30-day cumulative incidence of CRS in patients with low counts, for both Grade\u2009\u2265\u20092 (42.9% vs. 19.7%, p\u2009=\u20090.012) and Grade\u2009\u2265\u20093 CRS (17.9% vs. 1.3%, p\u2009&lt;\u20090.001). KyoTox-CRS, a risk-scoring system integrating these factors, effectively stratified these CRS risks. Early prediction of high-grade CRS based on the reticulocyte count at infusion may help to guide optimal risk-based management of CAR-T cell therapy.\n                  <\/jats:p>","DOI":"10.1007\/s12185-025-04109-7","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:12:28Z","timestamp":1763388748000},"page":"421-431","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low reticulocyte count at infusion is a risk factor for high-grade cytokine release syndrome in chimeric antigen receptor T cell therapy"],"prefix":"10.1007","volume":"123","author":[{"given":"Yusuke","family":"Tashiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9381-0421","authenticated-orcid":false,"given":"Tomoyasu","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Kitawaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyoshi","family":"Yoshinaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Shirakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momoko","family":"Nishikori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouhei","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Nagao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akifumi","family":"Takaori-Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"issue":"26","key":"4109_CR1","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","volume":"377","author":"SS Neelapu","year":"2017","unstructured":"Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. 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KY, ATK, and YA are members of the International Journal of Hematology Editorial Board.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was approved by the Institutional Review Board and Ethic Committee of Kyoto University (R3308). Written informed consent was obtained from all participating patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Data employed in this study are not publicly available due to ethical restrictions. Releasing these data would exceed the scope of patient consent for research use.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data sharing statement"}}]}}