Childhood Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI]-Late Effects from Childhood / Adolescent Hodgkin Lymphoma Therapy Children and adolescent survivors of Hodgkin lymphoma are at risk for numerous late complications of treatment related to radiation, specific chemotherapeutic exposures, and surgical staging. Adverse treatment effects may impact oral/dental health; musculoskeletal growth and development; endocrine, reproductive, cardiovascular and pulmonary function; and risk of secondary carcinogenesis. In the past 30 to 40 years, pediatric Hodgkin lymphoma therapy has changed dramatically to proactively limit exposure to radiation and chemotherapeutic agents, such as anthracyclines, alkylating agents, and bleomycin. When counseling individual patients about the risk for specific treatment complications, the era of treatment should be considered.

The following table summarizes late health effects observed in Hodgkin lymphoma survivors followed by a limited discussion of the common late effects. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for a full discussion of the late effects of cancer treatment in children and adolescents.)

Table 9. Treatment Complications Observed in Hodgkin Lymphoma Survivors

Health Effects	Predisposing Therapy	Clinical Manifestations
Oral/dental	Any chemotherapy in a patient who has not developed permanent dentition	Dental maldevelopment (tooth/root agenesis, microdontia, root thinning and shortening, enamel dysplasia)
	Radiation impacting oral cavity and salivary glands	Salivary gland dysfunction
		Xerostomia
		Accelerated dental decay
		Periodontal disease
Thyroid	Radiation impacting thyroid gland	Hypothyroidism
		Hyperthyroidism
		Thyroid nodules
Cardiovascular	Radiation impacting cardiovascular structures	Subclinical left ventricular dysfunction
		Cardiomyopathy
		Pericarditis
		Heart valve dysfunction
		Conduction disorder
		Coronary, carotid, subclavian vascular disease
		Myocardial infarction
		Stroke
	Anthracycline chemotherapy	Subclinical left ventricular dysfunction
		Cardiomyopathy
		Congestive heart failure
Pulmonary	Radiation impacting the lungs	Subclinical pulmonary dysfunction
	Bleomycin	Pulmonary fibrosis
Musculoskeletal	Radiation of musculoskeletal tissues in any patient who is not skeletally mature	Growth impairment
	Glucocorticosteroids	Bone mineral density deficit
		MS
Reproductive	Alkylating agent chemotherapy	Hypogonadism
	Gonadal irradiation	Infertility
Immune	Splenectomy	Overwhelming post-splenectomy sepsis
Subsequent neoplasm or disease	Alkylating agent chemotherapy	Myelodysplasia/acute myeloid leukemia
	Epipodophyllotoxins	Myelodysplasia/acute myeloid leukemia
	Radiation	Solid benign and malignant neoplasms

Male Gonadal Toxicity

• Gonadal radiation and alkylating agent chemotherapy may produce testicular Leydig cell or germ cell dysfunction with risk related to cumulative dose of both modalities.
• Hypoandrogenism associated with Leydig cell dysfunction may manifest as lack of sexual development; small, atrophic testicles; and sexual dysfunction. Hypoandrogenism also increases the risk of osteoporosis and metabolic disorders associated with chronic disease.[1,2]
• Infertility caused by azoospermia is the most common manifestation of gonadal toxicity. Some pubertal male patients will have impaired spermatogenesis before they begin therapy.[3,4]
• The prepubertal testicle is likely equally or slightly less sensitive to chemotherapy compared with the pubertal testicle. Pubertal status is not protective of chemotherapy-associated gonadal toxicity.[5,6]
• Testicular Leydig cells are relatively resistant to treatment toxicity compared with testicular germ cells. Survivors who are azoospermic after gonadal toxic therapy may maintain adequate testosterone production.[5,6,7]
• Chemotherapy regimens that include no alkylating agents such as ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine), ABVE (doxorubicin [Adriamycin], bleomycin, vincristine, etoposide), OEPA (vincristine [Oncovin], etoposide, prednisone, doxorubicin [Adriamycin]), or VAMP (vincristine, doxorubicin [Adriamycin], methotrexate, prednisone) are not associated with male infertility.
• Chemotherapy regimens including more than one alkylating agent, usually procarbazine in conjunction with cyclophosphamide (i.e., COPP [cyclophosphamide, vincristine (Oncovin), prednisone, procarbazine]), chlorambucil, or nitrogen mustard (MOPP) confer a high risk of permanent azoospermia if treatment exceeds three cycles.[8,9]
• Investigations evaluating germ cell function in relation to single alkylating agent exposure suggest that the incidence of permanent azoospermia will be low if the cyclophosphamide dose is less than 7.5 g/m².[6,10]

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