Long-term effects pf Hodgkin’s Lymphoma

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Summary

In malignant Hodgkin’s Lymphoma, chemotherapy and radiation therapy are also necessary to treat the disease. Delayed side effects such as hypothyroidism, muscle atrophy, infection, infertility and fatigue are common among patients with Hodgkin’s Lymphoma. HL survivors also have an increased risk for second malignancies and cardiovascular disease.

Introduction

Survival from malignant lymphomas such as Hodgkin’s Lymphoma has improved in the last decade. In malignant HL, chemotherapy and radiation therapy are also necessary for the treatment of the disease. Several research studies have also reported increased mortality and morbidity among cancer survivors. However, secondary malignancy and cardiovascular disease are the leading causes of death among long-term survivors of HL. Other delayed side effects such as hypothyroidism, muscle atrophy, infection, infertility, and fatigue have are also common among patients with HL. However, potential side effects related to long-term survival are not always related to treatment alone​1​.

Second malignancies (SM)

A second malignancy is any malignancy that develops after the healing of a malignant tumor. Hence, recurrences and metastases with the same malignancy as the first malignancy are not considered SM. The second malignancy is also one of the serious late-onset effects of HL treatment. It is also a major cause of premature death in long-term Hodgkin’s Lymphoma survivors. Several studies have reported that the incidence of SM increases after an incubation period of 10 years, especially in people younger than 40 years of age​2,3​. 

However, radiation therapy has been reported as a major cause of treatment-related solid tumors. Breast, thyroid, lung and gastrointestinal cancers are the second most common solid malignancies associated with Hodgkin’s Lymphoma radiation therapy.

Cardiovascular disease (CVD)

CVD is the second most common reason for death among HL survivors. There is also an increased risk of coronary artery disease, valvular disease, congestive heart failure, pericardial disease, stroke, arrhythmias and sudden cardiac death​4​. Microvascular, as well as arterial inflammation, is thought to be the major cause of radiation therapy-induced CVD. However, with SM, the risk of CVD among long-term survivors of Hodgkin’s Lymphoma is most pronounced in younger people who receive treatment. Because the mantle field contains sleep vessels, there is a risk of accelerating the atherosclerotic process​5​. In addition to the increased stroke risk due to valve disease, mantle radiation can damage sleep vessels and further increase the risk of stroke in HL survivors.

Other late effects

Hypothyroidism

Radiation causes atrophy of the thyroid gland, which increases the risk of developing hypothyroidism. Hypothyroidism develops in approximately 50% of patients undergoing mantle irradiation​6​. Clinical symptoms are those that affect the quality of life, such as depression, fatigue, constipation and bradycardia.

Muscular atrophy

Patients treated with mantle field radiation generally show characteristic neck muscle atrophy. Clinical symptoms range from asymptomatic to severely affecting the neck and limbs. People have different degrees of pain. And so, the root cause of muscle atrophy is believed to directly affect the muscles causing inflammation and fibrosis. In 2011 van Leeuwen-Segersinau et al. published a study where patients treated with mantle field radiation therapy for Hodgkin’s Lymphoma also developed a muscle atrophy​7​. Muscle atrophy outside the radiation field may be associated with neuropathic injury.

Fatigue

People who have had cancer for a long time have increased fatigue compared to the general population. It appears to be more common in Hodgkin’s Lymphoma survivors than in other cancers. Fatigue is characterized by extreme fatigue, loss of energy and loss of muscle strength. The presence of B symptoms at diagnosis (unexplained fever, weight loss, and night sweats), social isolation, and the presence of pulmonary toxicity (such as pneumonia and dyspnea) have been suggested as predispositions​8​.

Infections

In cell-mediated immune defenses, the spleen is particularly important for encapsulated bacterial organisms such as streptococcus pneumonia. Hence, splenectomy was the standard procedure for the treatment of HL. Studies have shown that high mortality increases the risk of infection in survivors of Hodgkin’s Lymphoma due to the most dangerous condition known as overwhelming post-splenectomy infection (OPSI)​9​.

Infertility

Treating cancer with chemotherapy at an early age can lead to infertility, depending on the gonadotoxic effect of the drug. While, the treatment causes DNA damage to the ovarian follicles and forms the Leydig cells that produce testosterone in the testes. Chemotherapy also damages the gonadal epithelial cells of the testis. Post-treatment male infertility is observed more frequently than female infertility​10​.

Reference

  1. Andersson A. Long-term side effects after treatment of Hodgkin’s lymphoma. DiVA. Published 2011. Accessed March 2022. https://www.diva-portal.org/smash/record.jsf?pid=diva2%3A412776&dswid=7955
  2. Ng A, Kenney L, Gilbert E, Travis L. Secondary malignancies across the age spectrum. Semin Radiat Oncol. 2010;20(1):67-78. doi:10.1016/j.semradonc.2009.09.002
  3. Metayer C, Lynch C, Clarke E, et al. Second cancers among long-term survivors of Hodgkin’s disease diagnosed in childhood and adolescence. J Clin Oncol. 2000;18(12):2435-2443. doi:10.1200/JCO.2000.18.12.2435
  4. Aleman B, van den, De B, et al. Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood. 2007;109(5):1878-1886. doi:10.1182/blood-2006-07-034405
  5. Hull M, Morris C, Pepine C, Mendenhall N. Valvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy. JAMA. 2003;290(21):2831-2837. doi:10.1001/jama.290.21.2831
  6. Hancock S, Cox R, McDougall I. Thyroid diseases after treatment of Hodgkin’s disease. N Engl J Med. 1991;325(9):599-605. doi:10.1056/NEJM199108293250902
  7. van LS, Dorresteijn L, Pillen S, Biesma D, Vogels O, van A. Progressive muscle atrophy and weakness after treatment by mantle field radiotherapy in Hodgkin lymphoma survivors. Int J Radiat Oncol Biol Phys. 2012;82(2):612-618. doi:10.1016/j.ijrobp.2010.11.064
  8. Greil R, Holzner B, Kemmler G, et al. Retrospective assessment of quality of life and treatment outcome in patients with Hodgkin’s disease from 1969 to 1994. Eur J Cancer. 1999;35(5):698-706. doi:10.1016/s0959-8049(99)00025-8
  9. Lynch A, Kapila R. Overwhelming postsplenectomy infection. Infect Dis Clin North Am. 1996;10(4):693-707. doi:10.1016/s0891-5520(05)70322-6
  10. Whitehead E, Shalet S, Blackledge G, Todd I, Crowther D, Beardwell C. The effects of Hodgkin’s disease and combination chemotherapy on gonadal function in the adult male. Cancer. 1982;49(3):418-422. doi:10.1002/1097-0142(19820201)49:3<418::aid-cncr2820490304>3.0.co;2-a