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Persistent peripheral blood EBV-DNA positive with high expression of PD-L1 and upregulation of CD4 + CD25 + T cell ratio in early stage NK/T cell lymphoma patients may predict worse outcome

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Abstract

Although gemcitabine, oxaliplatin and L-asparaginase/pegylated asparaginase (P-GEMOX) treatment for early-stage extranodal natural killer/T cell lymphoma (ENKTL) is effective, some patients die within 1 year of diagnosis. We attempted to determine an optimal biomarker for identifying such patients. We enrolled 71 patients with ENKTL who received P-GEMOX between January 2011 and January 2014. We classified the patients according to the outcome into worse (died within 1 year) or better groups (survival time ≥ 3, 4 or 5 years). The area under the curve (AUC) was determined to identify the optimal biomarker for differentiating the groups. The AUC was highest in patients who were plasma Epstein–Barr virus (EBV) DNA-positive post-treatment. The AUC was 0.82, 0.86 and 0.86 when the worse group was compared to the better group, respectively. Among the post-treatment EBV DNA-positive patients, as compared to EBV DNA-negative patients, pre-treatment EBV DNA-positive patients had a higher proportion of CD4 + CD25 + T cells. There was higher programmed cell death protein ligand-1(PD-L1) expression in post-treatment EBV DNA-positive patients. Post-treatment positive EBV DNA status maybe a useful biomarker of worse outcomes in early stage ENKTL.

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Acknowledgments

We thank the pathologists Dr. Jie-wei Chen and Xin-ke Zhang for their pathological review and we also thank the radiologist Dr. Zi-zheng Xiao for their imaging review of the patients included in this study.

Funding

This study was funded by the National Natural Scientific Research Fund of China (grant number 8150010416).

Author information

Author notes

  1. Peng-fei Li, Yi-ze Mao and Bing Bai contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Guangzhou, China

    Peng-fei Li, Yi-ze Mao, Bing Bai, Yan Gao, Zhi-ming Li, Wen-qi Jiang & Hui-qiang Huang

  2. Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, Guangdong, China

    Peng-fei Li, Yi-ze Mao, Bing Bai, Yan Gao, Zhi-ming Li, Wen-qi Jiang & Hui-qiang Huang

  3. Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Yu-jing Zhang

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  1. Peng-fei Li
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Contributions

Conceived and designed the study: Peng-fei Li and Yi-ze Mao. Performed the study: Peng-fei Li, Yu-jing Zhang, Zhi-ming Li, Wen-qi Jiang and Hui-qiang Hui. Analysed the data: Yan Gao and Bing Bai. Wrote the paper: Peng-fei Li and Yi-ze Mao.

Corresponding author

Correspondence to Hui-qiang Huang.

Ethics declarations

Ethics approval and consent to participate

As a retrospective analysis of prognostic factors, no approval from the Regional Committee for Medical and Health Research Ethics was necessary.

Consent for publication

We obtained informed consent for collecting and publishing medical information from all patients at their first visit.

Conflict of interest

The authors declare that they have no conflict of interests.

Electronic supplementary material

Supplementary Figure 1

EBV DNA levels decreased after treatment in 49 of 71 patients. (PNG 654 kb)

High resolution image (TIF 1847 kb)

Supplementary Figure 2

The OS and PFS of the patients with ≦4 cycles and > 4 cycles of P-GEMOX. (PNG 311 kb)

High resolution image (TIF 450 kb)

Supplementary Table 1

(DOC 49 kb)

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Li, Pf., Mao, Yz., Bai, B. et al. Persistent peripheral blood EBV-DNA positive with high expression of PD-L1 and upregulation of CD4 + CD25 + T cell ratio in early stage NK/T cell lymphoma patients may predict worse outcome. Ann Hematol 97, 2381–2389 (2018). https://doi.org/10.1007/s00277-018-3467-6

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  • DOI: https://doi.org/10.1007/s00277-018-3467-6

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