Evidence map›Paper›PMID 40207715›Full record

Trial reportHaematologica2025

Dynamic change in Epstein-Barr virus DNA predicts prognosis in early stage natural killer/T-cell lymphoma with pegaspargase-based treatment: long-term follow-up and biomarker analysis from the NHL-004 multicenter randomized study.

Huijuan Zhong, Shu Cheng, Jie Xiong, Jiayi Chen, Rongji Mu, Haoxu Yang, Hongmei Yi, Qi Song, Hao Zhang, Yu Hu and 42 more

Abstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Haematologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
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  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

52 authors.

Huijuan ZhongShanghai 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.
Shu ChengShanghai 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.
Jie XiongShanghai 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.
Jiayi ChenDepartment of Radiation Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
Rongji MuClinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai.
Haoxu YangShanghai 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.
Hongmei YiDepartment of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
Qi SongDepartment of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
Hao ZhangDepartment of Otolaryngology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
Yu HuInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei.
Guohui CuiInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei.
Juying WeiDepartment of Hematology, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang.
Xi ZhangDepartment of Hematology, Xinqiao Hospital, Chongqing.
Bing XuDepartment of Hematology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian.
Wenbin QianDepartment of Hematology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang.
Xiaobing HuangInstitute of Hematology, Department of Hematology, Sichuan Provincial People's Hospital, Chengdu, Sichuan.
Ming HouDepartment of Hematology, Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong.
Feng YanDepartment of Hematology, Third Affiliated Hospital of Suzhou University, First People's Hospital of Changzhou, Changzhou, Jiangsu.
Xin WangDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong.
Yongping SongDepartment of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan.
Yuanhua LiuDepartment of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu.
Xuejun MaDepartment of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai.
Jianda HuDepartment of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Department of Hematology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian.
Fei LiDepartment of Hematology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi.
Chongyang WuDepartment of Hematology, Second Hospital of Lanzhou University, Lanzhou, Gansu.
Junmin ChenDepartment of Hematology and Rheumatology, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian.
Li YuDepartment of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi.
Ou BaiDepartment of Hematology, First Hospital of Jilin University, Changchun, Jilin.
Jingyan XuDepartment of Hematology, Nanjing Drum Tower Hospital, Nanjing, Jiangsu.
Zunmin ZhuDepartment of Hematology, Henan Province People's Hospital, Zhengzhou, Henan.
Li LiuDepartment of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi.
Xin ZhouDepartment of Hematology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu.
Li HuangDepartment of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Hematology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan.
Yin TongDepartment of Hematology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, Shanghai.
Ting NiuDepartment of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan.
Depei WuFirst Affiliated Hospital of Soochow University, Suzhou, Jiangsu.
Xufeng JiangDepartment of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
Chaofu WangDepartment of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
Binshen OuyangDepartment of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
Gang CaiDepartment of Radiation Oncology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
Biao LiDepartment of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai.
Jia LiuDepartment of Hematology, Xinqiao Hospital, Chongqing.
Zhifeng LiDepartment of Hematology, First Affiliated Hospital of Xiamen University, Xiamen, Fujian.
Rong XiaoInstitute of Hematology, Department of Hematology, Sichuan Provincial People's Hospital, Chengdu, Sichuan.
Luqun WangDepartment of Hematology, Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, Shandong.
Yujie JiangDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong.
Yanyan LiuDepartment of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan.
Xiaoyun ZhengDepartment of Hematology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian.
Pengpeng XuShanghai 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.
Li WangShanghai 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.
Saijuan ChenShanghai 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; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai.
Wei-Li ZhaoShanghai 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; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai. zhao.weili@yahoo.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The multi-center randomized phase III NHL-004 study compared etoposide, dexamethasone and pegaspargase (ESA) versus the methotrexate, etoposide, dexamethasone and pegaspargase (MESA) regimen, combined with sandwiched radiotherapy, in newly diagnosed early-stage nasal natural killer / T-cell lymphoma (NKTCL). Here we report the long-term outcomes (median follow-up, 64 months) and biomarker analysis. A total of 256 eligible patients aged 14-70 years were randomly assigned (1:1) to the ESA or the MESA arm. The 5-year progression-free survival (PFS) rates were 80.3% and 74.9% in the ESA and MESA arms (hazard ratio [HR]=0.78 [95% CI: 0.46-1.33], P=0.371), and the 5-year overall survival (OS) rates were 85.1% and 80.9% (HR=0.74 [95% CI: 0.40-1.37], P=0.332), respectively. No new safety signals related to treatments were observed. Interim plasma Epstein-Barr virus (EBV) DNA positivity and stable disease / progressive disease response were independent predictors of inferior PFS and OS. No prognostic significance was observed according to molecular subtypes. Interim EBV DNA positivity correlated with up-regulated chromatin remodeling alterations, immune escape-related genes, and decreased infiltrating monocytes / M1 macrophages. With low toxicity, non-intravenous administration, and an outpatient design, ESA with sandwiched radiotherapy achieved long-term durable response in patients with newly diagnosed early-stage NKTCL. Dynamic monitoring of plasma EBV DNA provided a clinical rationale for future mechanism-based therapy in NKTCL.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsDNA, ViralEpstein-Barr Virus InfectionsHerpesvirus 4, HumanLymphoma, Extranodal NK-T-CellAdolescentAdultAgedAsparaginaseBiomarkers, TumorDexamethasoneEtoposideFemaleFollow-Up StudiesHumansMaleAsparaginaseBiomarkers, TumorDexamethasoneDNA, ViralEtoposideMethotrexatepegaspargasePolyethylene Glycols

Identifiers

PMID40207715
PMCPMC12580706

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.