The Prognostic Role of Circulating Epstein-Barr Virus DNA Copy Number in Angioimmunoblastic T-Cell Lymphoma Treated with Dose-Adjusted EPOCH

Cancer Res Treat. 2019 Jan;51(1):150-157. doi: 10.4143/crt.2017.476. Epub 2018 Apr 2.

Abstract

Purpose: Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens.

Materials and methods: Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen.

Results: Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNA‒positive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median follow-up was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressive-free survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNA‒positive and EBV DNA‒negative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNA‒positive group than in the EBV DNA‒negative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response.

Conclusion: Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.

Keywords: Angioimmunoblastic T-cell lymphoma; Epstein-Barr virus DNA; Prognosis; Survival.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacology
  • DNA Copy Number Variations / drug effects*
  • DNA, Viral / drug effects
  • DNA, Viral / genetics
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology
  • Epstein-Barr Virus Infections / blood
  • Epstein-Barr Virus Infections / drug therapy*
  • Epstein-Barr Virus Infections / virology
  • Etoposide / administration & dosage
  • Etoposide / pharmacology
  • Female
  • Herpesvirus 4, Human / drug effects
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Lymphocyte Count
  • Lymphoma, T-Cell / blood
  • Lymphoma, T-Cell / drug therapy*
  • Lymphoma, T-Cell / virology
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Prednisone / pharmacology
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vincristine / pharmacology

Substances

  • DNA, Viral
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • EPOCH protocol