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Late Effects of Long-Term Survivors of Hodgkin's Disease
Ernest H. Rosenbaum, MD

Late effects can include fatal infections, especially for those who've undergone laparotomy and splenectomy - need for a complete vaccination program - with prompt antibiotic treatment for fevers in asplenic (post-splenectomy) patients. Subsequent abnormalities in pulmonary function, hypothyroidism, fatigue, infertility, and psychosocial distress are common. Most are not life-threatening but affect quality of life.

The occurrence of second malignancies has been described over the last thirty-five years, including acute leukemia secondary to alkylating agents (poor prognosis) and development of non-Hodgkin's lymphoma, with an inferior prognosis.

After a latency of over ten years, secondary solid tumors are noted. The most common are breast and lung cancers. Breast cancer second malignancies usually occur ten to fifteen plus years post initial treatment, and the risk has ranged in various studies from 12-42%. This was more prominent with older techniques of radiation therapy to the left chest and mediastinum, usually after a dose of 28 Gy or higher.

Lung cancer, with a relative risk of 3- to 7-times that of the general population following Hodgkin's disease therapy, has a poor prognosis with a median survival of usually less than a year. Radiation therapy is usually not an option, as it has already been done as part of the Hodgkins mantle therapy field. Smokers of greater than ten-pack years had a six-fold increased risk of lung cancer than those with a one-pack year history of smoking.

There's a wide variety of cardiac complications as described above, including non-coronary vascular disease (aortic and mitral valves), non-coronary arteriosclerotic disease, including strokes and transient ischemic attacks (TIAs), carotid artery stenosis, and subclavian artery stenosis, where low-neck radiation therapy was included in the field.

Pulmonary dysfunction and physiologic decline post therapy often relate to Bleomycin and chest irradiation. Bleomycin toxicity ranges between 18 and 40% and can be fatal and radiation pneumonitis has about a 3% risk. There is a risk alert on the use of oxygen post Bleomycin therapy.

Other problems include the risk of infections, especially in those who've had a splenectomy and have fever and the need for Haemophilus influenza B vaccine, zoster vaccine, pneumococcal polysaccharide vaccine, and meningococcal polysaccharide vaccine are important.

Hypothyroidism occurs in about 30% of patients after mantle irradiation. Most cases occur two to three years after treatment, and assessment of an elevated thyroid stimulating hormone (TSH) can usually make a diagnosis. Replacement therapy is successful.

Sterility. Changes in the chemotherapy program, using ABVD (Adriamycin, Bleomycin, Vinblastine, and Decarbazine {Procarbazine}) as replacement for nitrogen mustard (Mechlorethamine), Oncovin, and Prednisone and, also by use of the Stanford V, (Bleomycin, Etoposide, Doxorubicin (Adriamycin), cyclophosphamide, Vincristine, Procarbazine and Prednisone), has reduced the risk of sterility. Those receiving ovarian transposition diaphragmatic Hodgkin's disease radiation therapy sometimes have the ovaries removed laterally, (oophoroplexy), and men receiving 4-6 Gy of fractionated radiation therapy to the testes will result in permanent azoospermia in most men. 8-10 Gy of ovarian radiation therapy can result in ovarian failure; although, children may still maintain ovarian function.

Sperm banking for men and oophoroexy for women wishing to preserve fertility can be helpful.

Fatigue is a major problem in survivors, and if anemia, hypothyroidism, cardiac and immune dysfunction, and muscular atrophy due to deconditioning are not problems, depression and psychological distress are found to be contributory. Psychosocial support, exercise, and good nutrition may help relieve symptoms.

Psychological distress for any form of cancer is common, as it's estimated that up to 30% of cancer patients have distress/depression. Psychological support and sometimes medication can be of help.

In summary, there are many types of complications, side effects and late recurrences of toxicities and second cancers noted in patients treated for Hodgkin's disease, and supportive care, knowledge about how to handle these problems and treatments, as well as improving lifestyle habits with diet, exercise and good preventive and diagnostic knowledge and techniques can help reduce some of the risks that can occur.

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