{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:06:24Z","timestamp":1776254784211,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is a rare clinical disease that is highly challenging to diagnose, has a low long-term survival rate and a high mortality rate. Currently, due to the particularity of HLH and the lack of effective understanding of the severity and prognosis of the disease in clinical practice, HLH patients are often missed or misdiagnosed in clinical practice, causing them to miss the best opportunity for diagnosis and treatment. This study aimed to retrospectively summarize and analyze the clinical characteristics, diagnosis and treatment, and prognosis of HLH patients from four medical centers, aiming to explore the risk factors affecting the prognosis of HLH patients and further enhance the understanding of HLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The clinical data of 162 patients with HLH diagnosed in four medical centers from May 2017 to May 2025 were collected. The general conditions, laboratory results, diagnosis and treatment processes, and prognosis of these patients were analyzed, and univariate and multivariate analyses of prognostic factors were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 162 HLH patients were included in this study, of whom 90 cases survived (55.56%), 72 cases died (44.44%), and there were 78 male patients (48.15%) and 84 female patients (51.85%), with a median age at onset of 52\u202fyears (range: 1\u201383\u202fyears). The most common etiological factor was Epstein\u2013Barr virus (EBV) infection, and the primary presenting symptom was fever. First-line treatment primarily involved anti-infective therapy and symptomatic management, which was administered to 147 cases (90.74%). Prognostic analysis revealed that age, history of malignancy, infection history, presence of dermatological symptoms, APTT, INR, PCT, CRP, TG, TBIL, ferritin level, sCD25, lactate, SOFA score and time to treatment initiation, glucocorticoid monotherapy, gamma globulin treatment were significantly associated with patient outcomes in HLH. Tumor history, ferritin level, sCD25, lactate, SOFA score, time to treatment initiation, gamma globulin treatment were independent risk factors for mortality. Univariate Cox regression analysis identified that age, tumor history, history of rheumatic and autoimmune disorders, CRP, ferritin level, sCD25, lactate, SOFA score and time to treatment initiation, chemotherapy, glucocorticoid monotherapy, gamma globulin treatment were significant prognostic factors for OS in HLH patients. Multivariate analysis confirmed that tumor history, CRP, ferritin level, sCD25, lactate, SOFA score and time to treatment initiation, chemotherapy, glucocorticoid monotherapy, gamma globulin treatment were independent prognostic factors affecting OS in HLH patients. Age, APTT, INR, ferritin level, SOFA score, time to treatment initiation, glucocorticoid monotherapy, gamma globulin treatment were independent prognostic factors affecting OS in infection-triggered HLH patients. While age, INR, ferritin level, SOFA score, time to treatment initiation, chemotherapy were independent prognostic factors affecting OS in malignancy-associated HLH patients. Combined therapy regimens (especially chemotherapy combined with gamma globulin, glucocorticoid combined with gamma globulin) showed better clinical efficacy and survival benefits in the treatment of HLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HLH is a rare clinical disease, EBV was the predominant trigger for HLH. Prognostic factors differed between infection- and malignancy-associated subgroups. Combined regimens, particularly those including gamma globulin, offered superior survival benefits, underscoring the need for etiology-specific treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1809705","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T11:20:31Z","timestamp":1776252031000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel perspectives on the rare hemophagocytic lymphohistiocytosis: insights from a multi-center retrospective cohort"],"prefix":"10.3389","volume":"13","author":[{"given":"Changkun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hematology, Ganzhou People\u2019s Hospital (The Affiliated Ganzhou Hospital of Nanchang University), Jiangxi Health Commission Key Laboratory of Leukemia","place":["Ganzhou, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanquan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Ganzhou People\u2019s Hospital (The Affiliated Ganzhou Hospital of Nanchang University), Jiangxi Health Commission Key Laboratory of Leukemia","place":["Ganzhou, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Affiliated Hospital of Putian University","place":["Putian, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hehui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Intensive Medicine (Comprehensive ICU), The First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianzhen","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Fujian Medical University Union Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuotao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Intensive Medicine (Comprehensive ICU), The First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Hematology, Fujian Medical University Union Hospital","place":["Fuzhou, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"101515","DOI":"10.1016\/j.berh.2020.101515","article-title":"Hemophagocytic lymphohistiocytosis: an update on pathogenesis, diagnosis, and therapy","volume":"34","author":"Griffin","year":"2020","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"5921","DOI":"10.3390\/ijms25115921","article-title":"Pathogenesis of hemophagocytic Lymphohistiocytosis\/macrophage activation syndrome: a case report and review of the literature","volume":"25","author":"Gioia","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1002\/jha2.113","article-title":"Adult secondary hemophagocytic lymphohistiocytosis","volume":"1","author":"Obayo","year":"2020","journal-title":"EJHaem"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"309","DOI":"10.4274\/balkanmedj.galenos.2022.2022-4-83","article-title":"Hemophagocytic Lymphohistiocytosis","volume":"39","author":"Ka\u00e7ar","year":"2022","journal-title":"Balkan Med J"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e15516","DOI":"10.1111\/ped.15516","article-title":"Rare diseases presenting with hemophagocytic lymphohistiocytosis","volume":"65","author":"Kanegane","year":"2023","journal-title":"Pediatr Int"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"153321","DOI":"10.1016\/j.prp.2020.153321","article-title":"Can we truly diagnose adult secondary hemophagocytic lymphohistiocytosis (HLH)? 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