Late complications of therapy

• Treatment-induced sterility is frequently seen in 9 after treatment with MOPP and MOPP-like regimens regardless of age (90% azoospermic 1 year after >6 courses); the ABVD regimen produces significantly less infertility. Abnormal menstruation due to MOPP is more common in women over 30 (60-70%) and less common in those <20 (20-30%).

• Premature menopause is more common after MOPP in older V.

• ABVD + mantle radiotherapy causes higher incidence of post-irradiation paramediastinal fibrosis causing persistent effort dyspnoea.

• Patients cured of HL are at 4 risk of a second malignancy with a relative risk of 6.4.

• Solid tumours (commonly breast, lung, melanoma, soft tissue sarcoma, stomach and thyroid) comprise >50% of second malignancies; proportion increases as follow-up lengthens; risk ~13% at 15 years and ~22% at 25 years; associated with radiotherapy and young age at time of treatment; 75% occur within radiation fields.

• Acute myeloblastic leukemia risk ~3% at 10 years after treatment; peak incidence between 5-9 years; risk 5 10 years after therapy; particularly associated with MOPP chemotherapy and age >40 and radiotherapy dose >30Gy to mediastinum; risk 10 years after ABVD <1%.

• NHL risk 7%; rises beyond 10 years and declines after 15 years; no clear association with type of therapy.

• Cardiac toxicity: myocardial infarction, radiation-induced pericarditis, valvular disease and congestive failure occur at an increased frequency in patients previously treated for HL; higher risk in patients <40 at treatment.

• Pulmonary toxicity: generally mild, usually asymptomatic changes in pulmonary function; associated with mediastinal irradiation and bleomycin containing chemotherapy (ABVD).

• Thyroid toxicity: 50% risk at 20 years after radiation to the neck and upper mediastinum; risk highest for ages 15-25; usually hypothyroidism, minority develop hyperthyroidism, Hashimoto's thyroiditis, nodules or thyroid cancer.

• Patients treated with HDT and autologous SCT have an increased incidence of myelodysplasia and AML and azoospermia in males and premature ovarian failure in females is usual.

1 Hasenclever, D. & Diehl, V. (1998) A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med, 339, 1506-1514 2 Canellos, G.P. et at. (1992) Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med, 327, 1478-1484 3 Loeffter, M. et at. (1998) Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group. J Clin Oncol, 16, 818-829.

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