Long‐Term Outcomes of a Stratified Treatment Regimen Based on Etoposide and Glucocorticoids in Children With Hemophagocytic Lymphohistiocytosis ( <scp>CCHG</scp> ‐ <scp>HLH</scp> ‐2018): A Multicenter, Single‐Arm Clinical Study

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The widely used HLH-1994/2004 protocols are primarily designed for primary HLH (pHLH). However, in Asia, particularly in China, secondary HLH (sHLH) is more prevalent, which may limit the efficacy of these protocols and increase treatment-related toxicity. To address this, we conducted a multicenter, prospective, single-arm clinical study to evaluate the CCHG-HLH-2018 protocol, a stratified treatment regimen based on glucocorticoids and etoposide, for pediatric HLH patients in China. A total of 286 patients from 20 centers were included, with a median follow-up of 64 months. Based on HLH-related indicators at onset, 64 patients (22.4%) were classified as low-risk group and 222 (77.6%) as high-risk group. The 5-year overall survival (OS) for all patients was 86.3% (95% CI, 81.7-89.8), with 96.9% (95% CI, 88.1-99.2) in low-risk group and 83.2% (95% CI, 77.6-87.5) in high-risk group (Holm-Bonferroni adjusted p = 0.006). The 5-year OS for pHLH patients was 72.9% (95% CI, 58.0-83.3), significantly lower than the 89.0% (95% CI, 84.3-92.4) for sHLH patients (Holm-Bonferroni adjusted p = 0.008). Among all patients, 54 (18.9%) achieved sustained remission without chemotherapy. No significant differences in OS and EFS were observed between high-risk patients receiving CSA-containing regimens and those receiving non-CSA regimens (p = 0.148, p = 0.107). However, exploratory subgroup analysis of idiopathic HLH patients suggested a trend toward improved survival with the CSA-containing regimen. The safety profile of the CCHG-HLH-2018 protocol was acceptable, with fewer adverse events in the low-risk group. Our findings suggest this stratified protocol is effective in reducing chemotherapy intensity for Chinese children with HLH. Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR1800017267.

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Journal
American Journal of Hematology
Published
2025-12-12
DOI
https://doi.org/10.1002/ajh.70158
Primary Topic
Autoimmune and Inflammatory Disorders Research
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article
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article

Long‐Term Outcomes of a Stratified Treatment Regimen Based on Etoposide and Glucocorticoids in Children With Hemophagocytic Lymphohistiocytosis ( CCHG ‐ HLH ‐2018): A Multicenter, Single‐Arm Clinical Study

Zishi Fang, Ang Wei, Rui Zhang, Liming Sun et al.
American Journal of Hematology
Autoimmune and Inflammatory Disorders Research
article

Long‐Term Outcomes of a Stratified Treatment Regimen Based on Etoposide and Glucocorticoids in Children With Hemophagocytic Lymphohistiocytosis ( CCHG ‐ HLH ‐2018): A Multicenter, Single‐Arm Clinical Study

Zishi Fang, Ang Wei, Rui Zhang, Liming Sun, Jingshi Wang, Jie Yu, Xiaojun Yuan, Jian‐Pei Fang, Shaoyan Hu, Tianyou Wang, Chenxin Zhou, Yunze Zhao, Rong Liu, Qing Zhang, Zhigang Li, Jian Wang, Dong Wang, Shilin Liu, Dongsheng Huang, Wenqian Wang, Jian Ge, Weihong Zhao, Xuerong Li, Aiguo Liu, Leping Zhang, Xiaoyan Wu, Yongmin Tang, Yongjun Fang, Yuan Sun, Wei Liu
article en

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The widely used HLH-1994/2004 protocols are primarily designed for primary HLH (pHLH). However, in Asia, particularly in China, secondary HLH (sHLH) is more prevalent, which may limit the efficacy of these protocols and increase treatment-related toxicity. To address this, we conducted a multicenter, prospective, single-arm clinical study to evaluate the CCHG-HLH-2018 protocol, a stratified treatment regimen based on glucocorticoids and etoposide, for pediatric HLH patients in China. A total of 286 patients from 20 centers were included, with a median follow-up of 64 months. Based on HLH-related indicators at onset, 64 patients (22.4%) were classified as low-risk group and 222 (77.6%) as high-risk group. The 5-year overall survival (OS) for all patients was 86.3% (95% CI, 81.7-89.8), with 96.9% (95% CI, 88.1-99.2) in low-risk group and 83.2% (95% CI, 77.6-87.5) in high-risk group (Holm-Bonferroni adjusted p = 0.006). The 5-year OS for pHLH patients was 72.9% (95% CI, 58.0-83.3), significantly lower than the 89.0% (95% CI, 84.3-92.4) for sHLH patients (Holm-Bonferroni adjusted p = 0.008). Among all patients, 54 (18.9%) achieved sustained remission without chemotherapy. No significant differences in OS and EFS were observed between high-risk patients receiving CSA-containing regimens and those receiving non-CSA regimens (p = 0.148, p = 0.107). However, exploratory subgroup analysis of idiopathic HLH patients suggested a trend toward improved survival with the CSA-containing regimen. The safety profile of the CCHG-HLH-2018 protocol was acceptable, with fewer adverse events in the low-risk group. Our findings suggest this stratified protocol is effective in reducing chemotherapy intensity for Chinese children with HLH. Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR1800017267.

American Journal of HematologyVol. 101(2)
Qingdao University (CN), Beijing Tongren Hospital (CN), Union Hospital (HK), Ministry of Education of the People's Republic of China (CN), Sun Yat-sen University (CN), Capital Medical University (CN), Soochow University (TW), Peking University (CN), XinHua Hospital (CN), Soochow University (CN), Sun Yat-sen Memorial Hospital (CN), Capital Institute of Pediatrics (CN), Zhengzhou Children's Hospital (CN), Children's Hospital of Zhejiang University (CN), Affiliated Hospital of Qingdao University (CN), Peking University People's Hospital (CN), Wuhan Union Hospital (CN), Peking University First Hospital (CN), Second Affiliated Hospital of Nanjing Medical University (CN), Beijing Children’s Hospital (CN), Beijing Friendship Hospital (CN), Anhui Provincial Children's Hospital (CN), Shenzhen Children's Hospital (CN), Beijing Shijitan Hospital (CN), Children's Hospital of Chongqing Medical University (CN), Tongji Hospital (CN), Children's Hospital of Capital Institute of Pediatrics (CN), Huazhong University of Science and Technology (CN), Chongqing Medical University (CN)
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Autoimmune and Inflammatory Disorders Research
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