Long-term follow-up of survivors of childhood Hodgkin's lymphoma suggests these patients have an increased risk of premature death, according to a presentation at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of second malignancies among survivors is well known, few studies prior to the current analysis had specifically addressed treatment-associated mortality after childhood Hodgkin's lymphoma.

The Childhood Cancer Survivor Study (CCSS) followed a cohort of survivors of childhood cancer diagnosed between 1970 and 1986. Childhood survivors of Hodgkin's lymphoma had a standardized mortality ratio of 8.3 compared with the overall population of the United States.

Presenter Sharon M. Castellino, MD, of the Wake Forest University School of Medicine, presented an analysis of mortality risk factors for these survivors. The overall study, a retrospectively assembled cohort with subsequent prospective follow-up, included 1,927 survivors of Hodgkin's lymphoma (13 percent of all participants). Patients have been followed for a median of 23 years for relapse beyond 5 years, occurrence of second malignancy, and grade 3 or 4 cardiovascular conditions.

The incidence of relapse by 20 years after diagnosis was 13.2 percent. The 30-year cumulative incidence of second malignancies was 25.3 percent in women and 10.6 percent in men. When breast cancer was eliminated from the analysis, the 30-year cumulative incidence of second malignancies in women was 10.9 percent, comparable with that for men.

There was no significant difference by gender in cumulative incidence of grade 3 and 4 cardiovascular conditions. Second malignancy and cardiac conditions were the leading causes of death for both men and women.

Results for all patients were analyzed separately in Cox proportional hazard models adjusted for patient demographics. In a multivariate analysis, chemotherapy with anthracyclines was a significant risk factor for mortality in men. Supradiaphragmatic and infradiaphragmatic radiotherapy were significant risk factors for mortality in women patients at all radiation doses.

Relapse was a significant predictor of mortality in women, whereas grade 3 and 4 cardiovascular conditions were associated with an increased mortality risk in all patients. Second malignancies also decreased survival for all patients, with a stronger effect in men than women.

Castellino concluded that therapy-related morbidity and premature mortality is a trend as the cohort ages. She suggested that aging survivors and their health care providers should have a heightened awareness of second malignancies and cardiovascular risks and perform earlier targeted screening for these conditions.