{ "abstract": "Background\n\nFamilial hemophagocytic lymphohistiocytosis (FHLH) is classically pediatric, but adult-onset disease is increasingly recognized. Whether adult-onset FHLH differs from pediatric/adolescent-onset disease remains incompletely defined. We aimed to characterize age-related differences in a nationwide multicenter cohort of patients with FHLH in China.Methods\n\nWe conducted a nationwide multicenter retrospective study of 223 patients with FHLH from 27 centers in China. Genetic architecture, central nervous system (CNS) involvement, allogeneic hematopoietic stem cell transplantation (allo-HSCT), and survival were compared by age at onset, with adult-onset disease defined as onset at age ≥ 18 years and pediatric/adolescent-onset disease as onset at < 18 years.Results\n\nIn this cohort, adult-onset disease accounted for 54/223 cases (24.2%). In the PRF1/UNC13D subset (n = 192), higher non-truncating variant burden was associated with adult onset (unadjusted OR per additional recorded variant, 1.95; 95% CI, 1.17-3.39), although the association attenuated after adjustment for gene and zygosity (adjusted OR, 1.58; 95% CI, 0.94-2.75). Epstein-Barr virus (EBV) was the predominant documented trigger in adults. CNS involvement was common across age groups (46.4%), with uncertain prognostic significance. Adults underwent allo-HSCT less frequently (49.1% vs. 70.2%) and were less often in complete response before transplantation (15.4% vs. 46.8%). Adult onset remained associated with poorer overall survival after multivariable adjustment including time-dependent allo-HSCT (HR, 3.74; 95% CI, 1.96-7.12). Post-HSCT survival was also poorer in adults.Conclusion\n\nAdult-onset FHLH was associated with non-truncating variant enrichment and poorer overall and post-HSCT survival. These findings support considering inherited disease despite acquired triggers and careful assessment of disease control and transplant-related risks in adults with FHLH.", "abstract_shown": true, "affiliations": [ "Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.", "Beijing Jingdu Children's Hospital, Beijing, China.", "The Second Hospital of Tianjin Medical University, Tianjin, China.", "Beijing Children's Hospital, Capital Medical University, Beijing, China.", "Capital Children's Medical Center, Capital Institute of Pediatrics, Capital Medical University, Beijing, China.", "Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China.", "Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.", "The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.", "Department of Pediatric Hematology and Oncology, Children's Hospital, National Clinical Research Center for Children and Adolescents' Health and Diseases, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.", "The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.", "Department of Oncology, The Affiliated Children's Hospital of Xiangya, School of Medicine, Central South University (Hunan Children's Hospital), Changsha, Hunan, China.", "Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, Shandong, China.", "Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.", "Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, Guangdong, China.", "Department of Hematology and Oncology, Anhui Provincial Children's Hospital, Hefei, Anhui, China.", "Qilu Hospital of Shandong University, Jinan, Shandong, China.", "The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.", "Department of Hematology, Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital), Taiyuan, Shanxi, China.", "Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.", "Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.", "Department of Hematology, Civil Aviation General Hospital, Beijing, China.", "Department of Hematology, The First Hospital of Jilin University, Changchun, Jilin, China.", "Kunming Children's Hospital, Kunming, Yunnan, China.", "Department of Hematology and Oncology, Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China.", "Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, (Guizhou Provincial Children's Hospital), Zunyi, Guizhou, China.", "The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou, China.", "Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. ndyfy01238@ncu.edu.cn.", "Beijing Children's Hospital, Capital Medical University, Beijing, China. ruizh1973@126.com.", "Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. wangzhao@ccmu.edu.cn." ], "article_type": "research article", "arxiv": null, "author_total": 32, "authors": [ { "affs": [ 0 ], "name": "Yu Li" }, { "affs": [ 1 ], "name": "Yuan Sun" }, { "affs": [ 2 ], "name": "Jie Bai" }, { "affs": [ 3 ], "name": "Ruohan Yang" }, { "affs": [ 4 ], "name": "Rong Liu" }, { "affs": [ 4 ], "name": "Jing Cao" }, { "affs": [ 5 ], "name": "Meiling Liao" }, { "affs": [ 6 ], "name": "Yaping Wang" }, { "affs": [ 7 ], "name": "Jiaxu Qi" }, { "affs": [ 8 ], "name": "Zebin Luo" }, { "affs": [ 9 ], "name": "Dao Wang" }, { "affs": [ 10 ], "name": "Haixia Yang" }, { "affs": [ 11 ], "name": "Muyuan Ji" }, { "affs": [ 12 ], "name": "Yunyan He" }, { "affs": [ 13 ], "name": "Shilin Liu" }, { "affs": [ 14 ], "name": "Weiyu Kong" }, { "affs": [ 15 ], "name": "Xue Li" }, { "affs": [ 16 ], "name": "Yan Han" }, { "affs": [ 17 ], "name": "Taoli Suo" }, { "affs": [ 18 ], "name": "Kai Xue" }, { "affs": [ 19 ], "name": "Gan Fu" }, { "affs": [ 20 ], "name": "Yong Zhang" }, { "affs": [ 21 ], "name": "Sujun Gao" }, { "affs": [ 22 ], "name": "Tingting Cui" }, { "affs": [ 23 ], "name": "Chengyi Wang" }, { "affs": [ 24 ], "name": "Yan Chen" }, { "affs": [ 25 ], "name": "Zhencang Zhou" }, { "affs": [ 0 ], "name": "Jia Zhang" }, { "affs": [ 0 ], "name": "Jingshi Wang" }, { "affs": [ 26 ], "name": "Fei Li" }, { "affs": [ 27 ], "name": "Rui Zhang" }, { "affs": [ 28 ], "name": "Zhao Wang" } ], "bibtex": "https://research.draconitic.com/paper/e75qxkzycfz0h.bib", "cited_by": 0, "doi": "10.1186/s40364-026-01026-7", "fulltext_url": "https://europepmc.org/articles/PMC13721406", "id": "e75qxkzycfz0h", "issns": [ "2050-7771" ], "landing_url": "https://europepmc.org/article/MED/42958546", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Research" ], [ "openalex", "2720|Autoimmune and Inflammatory Disorders Research" ] ], "openalex": "W7224658994", "pdf_url": "https://europepmc.org/articles/PMC13721406?pdf=render", "pmcid": "PMC13721406", "pmid": "42958546", "published": "2026-10-28", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/e75qxkzycfz0h.ris", "sources": [ { "first_seen": "2026-11-01T00:20:36Z", "native_id": "MED:42958546", "source": "europepmc", "url": "https://europepmc.org/article/MED/42958546" }, { "first_seen": "2026-11-03T12:22:06Z", "native_id": "PMC13721406", "source": "pmc", "url": "https://doi.org/10.1186/s40364-026-01026-7" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2720|Autoimmune and Inflammatory Disorders Research", "subfield": "general" } ], "title": "Adult-onset familial hemophagocytic lymphohistiocytosis has distinct genetic architecture and outcomes: a nationwide multicenter cohort study in China.", "title_text": "Adult-onset familial hemophagocytic lymphohistiocytosis has distinct genetic architecture and outcomes: a nationwide multicenter cohort study in China.", "type": "peer-reviewed", "updated_at": "2026-11-03T12:22:06Z", "url": "https://research.draconitic.com/paper/e75qxkzycfz0h", "venue": "Biomarker research", "versions": [] }