Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease

Purpose: We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. Patients and Methods: Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (≥ 10 years of age at diagnosis) and 114 preadolescents (< 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. Results: At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were ≥ 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those with breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. Conclusion: Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.