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Peer-reviewedCC BY-NC-NDBiomarker research

Adult-onset familial hemophagocytic lymphohistiocytosis has distinct genetic architecture and outcomes: a nationwide multicenter cohort study in China.

  • Yu Li1
  • Yuan Sun2
  • Jie Bai3
  • Ruohan Yang4
  • Rong Liu5
  • Jing Cao5
  • Meiling Liao6
  • Yaping Wang7
  • Jiaxu Qi8
  • Zebin Luo9
  • Dao Wang10
  • Haixia Yang11
20 more authors
  • Muyuan Ji12
  • Yunyan He13
  • Shilin Liu14
  • Weiyu Kong15
  • Xue Li16
  • Yan Han17
  • Taoli Suo18
  • Kai Xue19
  • Gan Fu20
  • Yong Zhang21
  • Sujun Gao22
  • Tingting Cui23
  • Chengyi Wang24
  • Yan Chen25
  • Zhencang Zhou26
  • Jia Zhang1
  • Jingshi Wang1
  • Fei Li27
  • Rui Zhang28
  • Zhao Wang29
29 affiliations
  1. 1Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
  2. 2Beijing Jingdu Children's Hospital, Beijing, China.
  3. 3The Second Hospital of Tianjin Medical University, Tianjin, China.
  4. 4Beijing Children's Hospital, Capital Medical University, Beijing, China.
  5. 5Capital Children's Medical Center, Capital Institute of Pediatrics, Capital Medical University, Beijing, China.
  6. 6Department 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.
  7. 7Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  8. 8The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  9. 9Department 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.
  10. 10The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  11. 11Department of Oncology, The Affiliated Children's Hospital of Xiangya, School of Medicine, Central South University (Hunan Children's Hospital), Changsha, Hunan, China.
  12. 12Children's Hospital Affiliated to Shandong University (Jinan Children's Hospital), Jinan, Shandong, China.
  13. 13Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  14. 14Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, Guangdong, China.
  15. 15Department of Hematology and Oncology, Anhui Provincial Children's Hospital, Hefei, Anhui, China.
  16. 16Qilu Hospital of Shandong University, Jinan, Shandong, China.
  17. 17The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China.
  18. 18Department of Hematology, Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital), Taiyuan, Shanxi, China.
  19. 19Shanghai 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.
  20. 20Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  21. 21Department of Hematology, Civil Aviation General Hospital, Beijing, China.
  22. 22Department of Hematology, The First Hospital of Jilin University, Changchun, Jilin, China.
  23. 23Kunming Children's Hospital, Kunming, Yunnan, China.
  24. 24Department 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.
  25. 25Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, (Guizhou Provincial Children's Hospital), Zunyi, Guizhou, China.
  26. 26The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, Guizhou, China.
  27. 27Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. [email protected].
  28. 28Beijing Children's Hospital, Capital Medical University, Beijing, China. [email protected].
  29. 29Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. [email protected].
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Abstract

Background

Familial 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

We 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

In 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

Adult-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.

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Cite

BibTeXRIS
BibTeX
@article{li2026adultonset,
  title = {{Adult-onset familial hemophagocytic lymphohistiocytosis has distinct genetic architecture and outcomes: a nationwide multicenter cohort study in China.}},
  author = {Yu Li and Yuan Sun and Jie Bai and Ruohan Yang and Rong Liu and Jing Cao and Meiling Liao and Yaping Wang and Jiaxu Qi and Zebin Luo and Dao Wang and Haixia Yang and Muyuan Ji and Yunyan He and Shilin Liu and Weiyu Kong and Xue Li and Yan Han and Taoli Suo and Kai Xue and Gan Fu and Yong Zhang and Sujun Gao and Tingting Cui and Chengyi Wang and Yan Chen and Zhencang Zhou and Jia Zhang and Jingshi Wang and Fei Li and Rui Zhang and Zhao Wang},
  journal = {Biomarker research},
  year = {2026},
  month = oct,
  doi = {10.1186/s40364-026-01026-7},
  url = {https://europepmc.org/article/MED/42958546},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Adult-onset familial hemophagocytic lymphohistiocytosis has distinct genetic architecture and outcomes: a nationwide multicenter cohort study in China.
AU  - Yu Li
AU  - Yuan Sun
AU  - Jie Bai
AU  - Ruohan Yang
AU  - Rong Liu
AU  - Jing Cao
AU  - Meiling Liao
AU  - Yaping Wang
AU  - Jiaxu Qi
AU  - Zebin Luo
AU  - Dao Wang
AU  - Haixia Yang
AU  - Muyuan Ji
AU  - Yunyan He
AU  - Shilin Liu
AU  - Weiyu Kong
AU  - Xue Li
AU  - Yan Han
AU  - Taoli Suo
AU  - Kai Xue
AU  - Gan Fu
AU  - Yong Zhang
AU  - Sujun Gao
AU  - Tingting Cui
AU  - Chengyi Wang
AU  - Yan Chen
AU  - Zhencang Zhou
AU  - Jia Zhang
AU  - Jingshi Wang
AU  - Fei Li
AU  - Rui Zhang
AU  - Zhao Wang
PY  - 2026
DA  - 2026/10/28
JO  - Biomarker research
DO  - 10.1186/s40364-026-01026-7
UR  - https://europepmc.org/article/MED/42958546
AB  - Background  Familial 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  We 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  In 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  Adult-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.
SN  - 2050-7771
ER  -