{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:45:50Z","timestamp":1793148350234,"version":"4.5.0"},"reference-count":52,"publisher":"American Society of Hematology","issue":"9","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,26]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is an interferon gamma\u2013driven hyperinflammatory syndrome with high morbidity and mortality. Identifying reliable prognostic biomarkers is challenging due to various predisposing conditions and triggers. C-X-C-motif ligand 9 (CXCL9) is a clinically validated biomarker and surrogate marker of interferon gamma\u2013mediated inflammation. We aimed to identify the role of CXCL9 in predicting severe disease and death in adults with HLH using a multicenter retrospective cohort of consecutively hospitalized patients who underwent a clinical evaluation for HLH that included CXCL9 testing. Patients were classified as HLH if they met HLH-2004 and\/or HScore criteria. Conditional inference decision trees and Cox regression models were used to identify which clinical variables associated with acute mortality in patients with HLH. Overall, 171 patients were reviewed, and 126 patients met HLH criteria. The median age was 55 years (interquartile range, 40-66), with 62% male and 51% White. CXCL9 was markedly elevated in patients with HLH. Unbiased decision tree modeling, incorporating all clinical laboratory values, identified only CXCL9 of &amp;gt;16\u2009100 pg\/mL as the optimal predictor of inpatient mortality. Cox regression models demonstrated that CXCL9 of &amp;gt;16\u2009100 pg\/mL was significantly associated with 90-day mortality when controlling for important covariates. This shorter time to death in the elevated CXCL9 subgroup remained significant even after subdividing patients into those with malignancy (n = 53) and nonmalignancy HLH (n = 73). Continuous increases in CXCL9 within the cohort strongly associated with greater mortality. CXCL9 is a novel clinical marker that identifies high-risk HLH independent of underlying disease and could be used to select patients for early and aggressive targeted immunomodulatory therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025030976","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T15:23:37Z","timestamp":1765380217000},"page":"960-972","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":15,"title":["CXCL9 as a novel prognostic marker to identify high-risk adults with hemophagocytic lymphohistiocytosis"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-4934","authenticated-orcid":false,"given":"Joseph M.","family":"Rocco","sequence":"first","affiliation":[{"name":"1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1129-5129","authenticated-orcid":false,"given":"Joseph H.","family":"Oved","sequence":"additional","affiliation":[{"name":"2Pediatric Transplant and Cellular Therapy Service, Memorial Sloan Kettering Kids, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4515-740X","authenticated-orcid":false,"given":"Rikita J.","family":"Patel","sequence":"additional","affiliation":[{"name":"3Department of Medicine, New York\u2013Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Zara","family":"Herskovits","sequence":"additional","affiliation":[{"name":"4Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namitha","family":"Nair","sequence":"additional","affiliation":[{"name":"5Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4615-370X","authenticated-orcid":false,"given":"Bita","family":"Shakoory","sequence":"additional","affiliation":[{"name":"1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4793-5914","authenticated-orcid":false,"given":"Thomas E.","family":"Robertson","sequence":"additional","affiliation":[{"name":"6Medicine Institute, Allegheny Health Network, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6921-8086","authenticated-orcid":false,"given":"Rachel","family":"Dileo","sequence":"additional","affiliation":[{"name":"6Medicine Institute, Allegheny Health Network, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4447-1491","authenticated-orcid":false,"given":"Max W.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"6Medicine Institute, Allegheny Health Network, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4219-0503","authenticated-orcid":false,"given":"Christa S.","family":"Zerbe","sequence":"additional","affiliation":[{"name":"1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 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