Classical Hodgkin Lymphoma: From Past to Future-A Comprehensive Review of Pathophysiology and Therapeutic Advances

Abstract

Hodgkin lymphoma, a hematological malignancy of lymphoid origin that typically arises from germinal-center B cells, has an excellent overall prognosis. However, the treatment of patients who relapse or develop resistant disease still poses a substantial clinical and research challenge, even though current risk-adapted and response-based treatment techniques produce overall survival rates of over 95%. The appearance of late malignancies after the successful cure of primary or relapsed disease continues to be a major concern, mostly because of high survival rates. Particularly in pediatric HL patients, the chance of developing secondary leukemia is manifold compared to that in the general pediatric population, and the prognosis for patients with secondary leukemia is much worse than that for patients with other hematological malignancies. Therefore, it is crucial to develop clinically useful biomarkers to stratify patients according to their risk of late malignancies and determine which require intense treatment regimens to maintain the ideal balance between maximizing survival rates and avoiding late consequences. In this article, we review HL's epidemiology, risk factors, staging, molecular and genetic biomarkers, and treatments for children and adults, as well as treatment-related adverse events and the late development of secondary malignancies in patients with the disease.

Keywords: Hodgkin lymphoma; brentuximab; checkpoint inhibitors; chimeric antigen T cells; new drugs; targeted therapy.

Figure 1

Trends in survival after ASCT for patients with HL in the United States 2001–2019. Footnote: slide taken from CIBMTR US summary slides. (Reference: Auletta, J.J.; Kou, J.; Chen, M.; Shaw, B.E. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR US summary slides, 2021 [143]). Of note, the views expressed in this article are that of the authors and does not reflect the position of the Center for International Blood and Marrow Transplant Research.

Figure 2

Survival after ASCT or Allo-SCT for HL, in the United States, 2009–2019: slide taken from CIBMTR US summary slides. (Reference: Auletta, J.J.; Kou, J.; Chen, M.; Shaw, B.E. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR US summary slides, 2021 [143]).