Impact of Tumour Epstein-Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL

Mahdi Nohtani; Katerina Vrzalikova; Maha Ibrahim; Judith E Powell; Éanna Fennell; Susan Morgan; Richard Grundy; Keith McCarthy; Sarah Dewberry; Jan Bouchal; Katerina Bouchalova; Pamela Kearns; Paul G Murray

doi:10.3390/cancers14174297

Impact of Tumour Epstein-Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL

Cancers (Basel). 2022 Sep 1;14(17):4297. doi: 10.3390/cancers14174297.

Authors

Mahdi Nohtani^{1

2}, Katerina Vrzalikova³, Maha Ibrahim⁴, Judith E Powell⁵, Éanna Fennell^{1

2}, Susan Morgan⁶, Richard Grundy⁷, Keith McCarthy⁸, Sarah Dewberry⁹, Jan Bouchal¹⁰, Katerina Bouchalova¹¹, Pamela Kearns⁹, Paul G Murray^{2

10}

Affiliations

¹ Bernal Institute, University of Limerick, V94 T9PX Limerick, Ireland.
² School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland.
³ Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
⁴ Cancer Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut 71526, Egypt.
⁵ Department of Public Health & Epidemiology, University of Birmingham, Birmingham B15 2TT, UK.
⁶ Department of Histopathology, Sheffield Teaching Hospitals, Sheffield S10 2JF, UK.
⁷ Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
⁸ Department of Histopathology, Wye Valley NHS Trust, Hereford HR1 2ER, UK.
⁹ Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Sciences, College of Medicine and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
¹⁰ Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Palacky University, 77900 Olomouc, Czech Republic.
¹¹ Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic.

Abstract

In this study, we have re-evaluated how EBV status influences clinical outcome. To accomplish this, we performed a literature review of all studies that have reported the effect of EBV status on patient outcome and also explored the effect of EBV positivity on outcome in a clinical trial of children with cHL from the UK. Our literature review revealed that almost all studies of older adults/elderly patients have reported an adverse effect of an EBV-positive status on outcome. In younger adults with cHL, EBV-positive status was either associated with a moderate beneficial effect or no effect, and the results in children and adolescents were conflicting. Our own analysis of a series of 166 children with cHL revealed no difference in overall survival between EBV-positive and EBV-negative groups (p = 0.942, log rank test). However, EBV-positive subjects had significantly longer event-free survival (p = 0.0026). Positive latent membrane protein 1 (LMP1) status was associated with a significantly lower risk of treatment failure in a Cox regression model (HR = 0.21, p = 0.005). In models that controlled for age, gender, and stage, EBV status had a similar effect size and statistical significance. This study highlights the age-related impact of EBV status on outcome in cHL patients and suggests different pathogenic effects of EBV at different stages of life.

Keywords: Epstein–Barr virus (EBV); classic Hodgkin lymphoma (cHL); clinical trial.

Grants and funding

The authors acknowledge financial support from Blood Cancer UK and the Cancer Research UK Birmingham Centre, University of Birmingham, Birmingham, United Kingdom (KH). The work was also supported in part by a European Regional Development Fund Project (ENOCH: CZ.02.1.01/0.0/0.0/16_019/0000868).