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Hjalgrim et al. J Transl Genet Genom 2022;6:134-46 Journal of Translational
DOI: 10.20517/jtgg.2021.46
Genetics and Genomics

Review Open Access

Clinical significance of aetiological heterogeneity in
classical Hodgkin lymphoma

Henrik Hjalgrim 1,2,3,4 , Klaus Rostgaard 1,2
1
Danish Cancer Society Research Center, Danish Cancer Society, 49 Strandboulevarden, Copenhagen 2100, Denmark.
2
Department of Epidemiology Research, Statens Serum Institut, Copenhagen 2300, Denmark.
3
Department of Haematology, Rigshospitalet, Copenhagen 2100, Denmark.
4
Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark.
Correspondence to: Prof. Henrik Hjalgrim, Danish Cancer Society Research Center, Danish Cancer Society, 49
Strandboulevarden, Copenhagen 2100, Denmark. E-mail: hhj@cancer.dk.
How to cite this article: Hjalgrim H, Rostgaard K. Clinical significance of aetiological heterogeneity in classical Hodgkin
lymphoma. J Transl Genet Genom 2022;6:134-46. https://dx.doi.org/10.20517/jtgg.2021.46

Received: 18 Sep 2021 First Decision: 9 Nov 2021 Revised: 21 Dec 2021 Accepted: 12 Jan 2022 Published: 29 Mar 2022

Academic Editors: Susan L. Slager, Giulia De Falco, Jonathan C Strefford Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun
Chen

Abstract
In this review we present contemporary understanding of aetiological heterogeneity in Hodgkin lymphoma, discuss
how this may influence tumour phenotype and whether it does or may impact treatment outcomes. Many new
treatments are being tested in this era. We especially discuss T-cell therapy and immune checkpoint blockade,
because these two modern treatments are expected to have differential efficacy by the presence/absence of
Epstein-Barr virus in the malignant Hodgkin-Reed-Sternberg cells. Survival after Hodgkin lymphoma is excellent in
many patient strata with first-line treatment, but less so for patients with refractory or relapsing disease. On the
other hand, this good prognosis also means that very large trials are needed to demonstrate superior efficacy of
new treatment regimes. And our understanding of aetiological heterogeneity in Hodgkin lymphoma and how it
affects prognosis is hampered for the same reason. We discuss the potential for fine-tuning risk stratification and
treatment based on information that is little used today.

Keywords: Epstein-Barr virus, classical Hodgkin lymphoma, histology, age, sex, tumour micro environment, human
leukocyte antigen, checkpoint inhibitors

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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