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. 2018 Dec;97(12):2381-2389. doi: 10.1007/s00277-018-3467-6. Epub 2018 Aug 16.

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.

Keywords: Biomarker; Epstein–Barr virus; Immunity; Lymphoma; Overall survival; Programmed cell death protein ligand-1.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B7-H1 Antigen / biosynthesis*
  • Biomarkers, Tumor / blood*
  • DNA, Neoplasm / blood*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Herpesvirus 4, Human*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / blood*
  • Lymphocyte Count
  • Lymphoma, Extranodal NK-T-Cell* / blood
  • Lymphoma, Extranodal NK-T-Cell* / mortality
  • Lymphoma, Extranodal NK-T-Cell* / virology
  • Male
  • Middle Aged
  • Neoplasm Proteins / blood*
  • Predictive Value of Tests
  • Retrospective Studies
  • Survival Rate
  • T-Lymphocytes / metabolism*

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • DNA, Neoplasm
  • Interleukin-2 Receptor alpha Subunit
  • Neoplasm Proteins