Transfusion-related Epstein-Barr virus (EBV) infection: A multicenter prospective cohort study among pediatric recipients of hematopoietic stem cell transplants (TREASuRE study)

Transfusion. 2021 Jan;61(1):144-158. doi: 10.1111/trf.16149. Epub 2020 Oct 22.

Abstract

Background: Epstein-Barr virus (EBV) is carried in the blood of most adults, and transfusion-related infections have been reported. EBV is particularly deleterious in immunosuppressed transplant patients. The aim was to determine if EBV transmission occurred through leukodepleted blood product transfusion in pediatric recipients of hematopoietic stem cell transplants (HSCT).

Study design and methods: This prospective Canadian multi-center cohort study includes 156 allogeneic HSCT pediatric recipients. The association between EBV and transfusion was analyzed using Cox regressions. EBV infection, defined by a PCR+ test in the blood of seronegative recipients of an EBV-negative graft, was monitored in order to correlate the recipient EBV strain with that of the blood donors. EBV genotypes were determined by PCR amplification followed by DNA sequencing at two loci (EBNA3b and LMP1).

Results: No statistically significant associations were found between transfusions and EBV. One case of post-transplant EBV infection was identified among the 21 EBV-seronegative recipients receiving an EBV-negative graft. A total of 22 blood donors were retraced to determine whether the recipient's EBV strain matched that of a donor. One donor strain showed 100% sequence homology at the EBNA3b locus, but differed by one or two point mutations and by a 132-bp deletion at the LMP1 locus. The blood donor in question was alone among the 22 donors to show amplifiable virus in plasma. Blood from this donor readily produced an immortalized lymphoblastoid cell line in culture.

Conclusion: While considered a rare event, EBV transmission through transfusion may occur in the context of severe immunosuppression.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Donors / statistics & numerical data
  • Blood Transfusion / methods
  • Blood Transfusion / statistics & numerical data
  • Canada / epidemiology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / transmission*
  • Epstein-Barr Virus Infections / virology
  • Epstein-Barr Virus Nuclear Antigens / genetics
  • Female
  • Genotype
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunosuppression Therapy / adverse effects
  • Male
  • Prospective Studies
  • Transfusion Reaction / virology*
  • Transplant Recipients / statistics & numerical data*
  • Viral Matrix Proteins / genetics

Substances

  • EBNA-3B antigen
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Epstein-Barr Virus Nuclear Antigens
  • Viral Matrix Proteins

Grants and funding