Despite improvements in treatments, there is an increased risk for death unrelated to lymphoma among patients with classical Hodgkin lymphoma (cHL), though the causes of these risks are largely preventable, according to research published in the Journal of Clinical Oncology.

Prior to the 1990s, combination mechlorethamine, vincristine, procarbazine, and prednisone with radiotherapy was frequently used in the cHL setting, though, over the past 30 years, this regimen has been replaced with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). In addition, the use of frontline radiotherapy has significantly decreased over the same period.

These changes in therapy are linked to improved overall survival among patients with cHL, though analysis of overall mortality in this patient group has not been undertaken in recent years. For this study, researchers aimed to determine patterns in mortality in patients with cHL “treated with initial chemotherapy during an era characterized by widespread use of ABVD and diminishing use of radiotherapy.”

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Using United Stated population-based cancer registries, the researchers obtained data for 20,007 patients diagnosed with stage I or II (defined as early stage) or stage III or IV (defined as advanced stage) cHL. All patients were treated in 2000 to 2015, with follow-up through 2016.

Among the patients evaluated, 11,919 had early-stage disease and 8088 patients had advanced-stage disease. In the overall cohort, 3380 deaths were noted, 1321 (39%) of which were not linked to cHL.

Compared with the general population, patients with early-stage disease had a noncancer standardized mortality ratio (SMR) of 1.6 (95% CI, 1.4-1.7), and patients with advanced-stage disease had a noncancer SMR of 2.4 (95% CI, 2.2-2.6).

The highest estimated excess absolute risks (EARs) for death per 10,000 patient-years were for patients with heart disease (EAR, 15.1; SMR, 2.1), infection (EAR, 10.6; SMR, 3.9), interstitial lung disease (EAR, 9.7; SMR, 22.1), and adverse events caused by treatment (EAR, 7.4; SMR, 5.0).

Deaths linked to heart disease, interstitial lung disease, infection, adverse events from treatment, and nonhematologic cancers were more common among patients aged 60 to 74 years with advanced-stage disease.

“Patterns of excess deaths as a result of heart disease, [interstitial lung disease], infections, and [adverse events] support a need for close monitoring and intervention beginning at the time of cHL diagnosis to reduce mortality for all patients, with particular attention paid to those with advanced-stage cHL and who are diagnosed at older ages,” the authors wrote.


Dores GM, Curtis RE, Dalal NH, Linet MS, Morton LM. Cause-specific mortality following initial chemotherapy in a population-based cohort of patients with classical Hodgkin lymphoma, 2000-2016. J Clin Oncol. Published online September 18, 2020. doi:10.1200/JCO.20.00264