Hodgkin lymphoma (HL) is 1 of the most common cancers arising in adolescents and young adults, and 1 of the most curable. This was not the case when Thomas Hodgkin first described the “morbid appearances of the absorbent glands and spleen” in 1832; all 7 of the cases he described died of their disease, as no effective therapies were available. Today, the vast majority of adolescents and young adults diagnosed with HL will be long-term survivors, as a result of highly effective treatment regimens developed through cooperative group trials conducted during the last 5 decades.
The challenges of ongoing clinical research today are to advance the competing objectives of (1) further increasing the probability of long-term cures for all patients with HL while (2) eliminating the long-term effects of cytotoxic chemotherapy and radiotherapy, including organ dysfunction and risk of second malignancies. Highly active targeted agents, which are actively being developed as further insights into the abnormal biology of malignant lymphoma cells come to light, are moving forward to the clinic, with the goal of minimizing off-target organ toxicity. Risk stratification and response-based treatment approaches identify those who can be cured with less toxic regimens. As the bicentennial of Thomas Hodgkin’s initial description approaches, clinicians caring for patients with his eponymous disease are closer to being able to expect that all who are diagnosed will be cured without fear of residual disease- or severe treatment-related sequelae.
PATHOGENESIS AND EPIDEMIOLOGY
The predominant clinical presentation of classical HL (cHL) is notably different in developed versus developing countries, as well as between age groups. These and other epidemiologic observations suggest that the etiology of cHL is dependent on a complex interaction among environmental, infectious, and host factors.
Classical HL has a bimodal incidence, with a first peak among adolescents and young adults and another among adults in the seventh to eighth decade of life. The young adult form (ages 15–34 years) shows a predominance of the nodular sclerosing histologic subtype in white adolescents and young adults in developed countries. HL is uncommon among preadolescent children, where it is associated with poorer socioeconomic environments, male sex, Epstein-Barr virus (EBV) infection, and the mixed cellularity histologic subtype.
HL is more common in males than in females in all parts of the world. The gender ratio varies from 2:1 in Europe and America to over 3.5:1 in Asia. The male predominance is most marked in patients younger than age 10 years. In adolescents, the gender difference in incidence is less conspicuous, particularly for the nodular sclerosing histologic subtype.
A genetic predisposition to HL is suggested by the variation in incidence among racial and ethnic groups, familial aggregation of the disease, and association with specific human leukocyte antigens. Many investigators have observed concordance of HL in first-degree relatives, including sibling and parent–child pairs. Standardized incidence ratios range from 3-fold ...