Which secondary cancers are possible complications of Hodgkin lymphoma (Hodgkin disease) therapy?

Updated: Sep 12, 2018
  • Author: Bradley W Lash, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Secondary leukemias and solid tumors are significant causes of morbidity and mortality for patients who have received early therapies, including the MOPP regimen and mantle radiation therapy. With modern therapies that emphasize the widespread use of the ABVD and Stanford V regimens and the application of radiation to involved fields only, the incidence of secondary cancers is expected to be much lower.

The most common secondary malignancy following treatment for Hodgkin lymphoma is lung cancer. Both chemotherapy with alkylating agents and irradiation are associated with a 10-fold increased relative risk of lung cancer. Smoking can further increase the risk. In addition, retrospective data have suggested that survival is worse in Hodgkin lymphoma survivors who develop lung cancer compared with matched cohorts with de novo lung cancer. [103]

Myelodysplastic syndromes/acute myelogenous leukemia (MDS/AML) is a particular concern. In the Stanford case series, the projected risk for developing MDS/AML over a follow-up period of 35 years was 2%, and the relative risk compared with matched controls was 38%. The MOPP regimen is associated with an approximately 5% incidence of MDS/AML. With the ABVD regimen the risk is lower, less than 1%.

MDS/AML is usually seen in the first 3-8 years following treatment for Hodgkin lymphoma; subsequently, the risk appears to decline. These findings are consistent with the biology of secondary leukemias following alkylator therapy. MDS/AML usually develops in the context of an MDS with cytogenetic abnormalities in chromosomes 5 and/or 7. Exposure to alkylating agents (eg, the mechlorethamine used in the MOPP regimen) has been implicated.

Exposure to epipodophyllotoxins (etoposide and teniposide) may also result in AML, which generally develops within 3 years and is associated with chromosomal abnormalities at band 11q23.

Breast cancer is 19 times more likely to occur in patients treated with mantle radiation therapy when they are younger than 30 years. If female patients are exposed to chest radiation therapy when they are younger than 15 years, this relative risk increases to 136. MOPP chemotherapy also produces an increased risk for breast cancer when combined with XRT.

Patients in the Stanford case series were also found to have increased risks of developing a variety of other cancers. These include melanoma, non-Hodgkin lymphoma, soft-tissue sarcoma, salivary gland cancers, pancreatic cancers, and thyroid cancers.

A study by Swerdlow et al found that the risk of second malignancy from chemotherapy alone is lower and affects fewer anatomic sites than combined treatment modalities. The authors concluded the risk of second malignancy was slight after 15 years. [104]

Taken in aggregate, these trial results suggest that altering the treatment paradigms of Hodgkin lymphoma to maximize curability while preventing long-term complications should be a focus of ongoing research. Using the least amount of therapy required to cure the disease and minimize complications should be the goal. Early results have suggested that modification of treatment is feasible and have shown some decreased rates of secondary cancers. [105]

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