{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:51:05Z","timestamp":1791265865885,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ferritin elevation is frequently observed during cytokine release syndrome (CRS) following CAR T\u2010cell therapy; however, its independent clinical utility as a predictive or prognostic biomarker remains uncertain. We performed a systematic review critically evaluating the timing\u2010specific and context\u2010dependent role of ferritin in CRS risk stratification and outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Web of Science, and Scopus for studies evaluating ferritin in CAR T\u2010cell recipients. We performed structured qualitative synthesis with semi\u2010quantitative comparison across studies, including direction\u2010of\u2010effect analysis and threshold stratification. We also performed a meta\u2010analysis on the association of progression\u2010free survival (PFS) and overall survival (OS) based on pre\u2010infusion ferritin levels using a random\u2010effects model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifteen studies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091671) were included. Elevated pre\u2010infusion ferritin (commonly \u2265\u2009400\u2009ng\/mL) was associated with higher CRS incidence and severity in most studies (10\/12), but its independent predictive value was inconsistent. Post\u2010infusion ferritin demonstrated a consistent association with CRS severity across all studies (9\/9), with extreme elevations (&gt;\u200910,000\u2009ng\/mL) observed in high\u2010grade CRS. However, ferritin lacked specificity as a standalone biomarker and performed more robustly when integrated into multimarker models (e.g., cytokines, EASIX score). Survival associations were heterogeneous and likely confounded by disease burden and systemic inflammation. Interestingly, meta\u2010analysis showed that pre\u2010infusion ferritin levels were significantly associated with worse PFS [HR: 2.18 (1.74\u20132.73),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.00001,\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%] and worse OS [HR: 2.97 (2.22\u20133.97),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.00001,\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%]. Potential publication bias was not identified in this analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ferritin is best interpreted as a dynamic inflammatory correlate rather than an independent predictor of CRS. Its clinical utility in CRS prediction lies in risk enrichment when combined with other biomarkers and clinical scores, rather than as a standalone decision tool. Nevertheless, pre\u2010infusion levels may be useful in predicting worse PFS and OS given the standardization of timing, thresholds, and integration into predictive models.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72150","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:29:32Z","timestamp":1788420572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Ferritin Levels With Cytokine Release Syndrome in\n                    <scp>CAR<\/scp>\n                    T\u2010Cell Therapy: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"15","author":[{"given":"Ranjit","family":"Sah","sequence":"first","affiliation":[{"name":"BMC South, BMC Health System  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhinav","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"Beckman Research Institute, City of Hope Comprehensive Cancer Center  Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-3329","authenticated-orcid":false,"given":"Sangam","family":"Shah","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Tribhuvan University  Kathmandu Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4771-4089","authenticated-orcid":false,"given":"Rachana","family":"Mehta","sequence":"additional","affiliation":[{"name":"SR Sanjeevani Hospital  Siraha Nepal"},{"name":"Clinical Microbiology, RDC Manav Rachna International Institute of Research and Studies  Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjit","family":"Sah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed\u2010To\u2010Be\u2010University)  Pune Maharashtra India"},{"name":"Department of Public Health Dentistry Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth  Pune Maharashtra India"},{"name":"Department of Medicine Korea University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeeshan","family":"Solangi","sequence":"additional","affiliation":[{"name":"Department of Medicine BMC South, BMC Health System  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George P.","family":"Sorescu","sequence":"additional","affiliation":[{"name":"Lemuel Shattuck Hospital  Boston Massachusetts USA"},{"name":"Tufts University School of Medicine  Massachusetts 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