Pretreatment whole blood Epstein-Barr virus-DNA is a significant prognostic marker in patients with Hodgkin lymphoma

Ann Hematol. 2016 Apr;95(5):801-8. doi: 10.1007/s00277-016-2610-5. Epub 2016 Feb 17.

Abstract

Epstein-Barr virus (EBV) in the peripheral blood has become a significant predictor of clinical outcomes in EBV-associated Hodgkin lymphoma (HL). However, due to its relative rarity, prevalence and prognostic role of circulating EBV-DNA has not been well established in Asian patients. Seventy patients with newly diagnosed HL were prospectively registered between October 2007 and January 2013, and underwent pretreatment whole blood (WB) EBV-DNA quantitation using real-time polymerase chain reaction (RT-PCR). WB EBV-DNA in baseline and serial RT-PCR within 1 year were investigated. Clinicopathologic parameters of the patients according to pretreatment WB EBV-DNA were also explored. Twelve patients (17.1 %) demonstrated WB EBV-DNA(+), which was significantly associated to older age, advanced stages, frequent involvements of extranodal sites, low serum albumin and hemoglobin levels, and high international prognostic scores ≥2. Three-year event-free survival (EFS) and overall survival (OS) were significantly inferior in patients with pretreatment WB EBV-DNA(+) (53.5 vs 67.0 and 65.6 vs 90.2 %) (p < 0.032 and <0.01). Negatively conversed EBV-DNA within 1 year after chemotherapy also significantly affected favorable EFS (p < 0.01). Taken together, pretreatment WB EBV-DNA(+) may be a significant predictor of inferior EFS and OS over EBV-encoded RNA in situ hybridization (EBER-ISH)(+) in Korean patients with HL. Serial EBV-DNA monitoring following chemotherapy also seems helpful to predict survival outcomes.

Keywords: DNA; EBV; Hodgkin disease; Prognosis; Whole blood.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asian People / statistics & numerical data
  • Biomarkers
  • Bleomycin / administration & dosage
  • DNA, Viral / blood*
  • Dacarbazine / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Epstein-Barr Virus Infections / blood*
  • Epstein-Barr Virus Infections / ethnology
  • Epstein-Barr Virus Infections / virology
  • Female
  • Herpesvirus 4, Human / isolation & purification*
  • Hodgkin Disease / blood*
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / ethnology
  • Hodgkin Disease / virology
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Viral / analysis
  • Real-Time Polymerase Chain Reaction
  • Reed-Sternberg Cells / chemistry
  • Reed-Sternberg Cells / virology
  • Republic of Korea / epidemiology
  • Tumor Virus Infections / blood*
  • Tumor Virus Infections / ethnology
  • Tumor Virus Infections / virology
  • Vinblastine / administration & dosage
  • Viremia / blood*
  • Viremia / virology
  • Young Adult

Substances

  • Biomarkers
  • DNA, Viral
  • Epstein-Barr virus encoded RNA 1
  • Epstein-Barr virus encoded RNA 2
  • RNA, Viral
  • Bleomycin
  • Vinblastine
  • Dacarbazine
  • Doxorubicin

Supplementary concepts

  • ABVD protocol