Organ transplant recipients more likely to develop aggressive melanoma

Organ transplant recipients are twice as likely to develop melanoma as people who do not undergo a transplant, and three times more likely to die of the dangerous skin cancer, suggests new research published in the Journal of Investigative Dermatology (2015; doi:10.1038/jid.2015.312).

The findings suggest that the immunosuppressive medications that transplant recipients receive to keep them from rejecting their new organs, especially the high doses administered at the time of transplant, may make them more susceptible to later stage cancers that are harder to cure. The researchers found that transplant recipients were four times more likely to be diagnosed with regional stage melanoma, which has already begun to spread to other parts of the body.

"We knew that melanoma was more likely in transplant recipients, but we thought it might be a function of intensive screening since they are very likely to develop less deadly forms of skin cancer and are checked regularly by dermatologists," said first author Hilary A. Robbins, MSPH, a PhD student in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. She conducted much of the research while at the National Cancer Institute.

"To the contrary, we were surprised to see that transplant recipients were particularly at risk for developing melanomas that weren't found until they had already spread."

The risk of aggressive melanomas was especially increased within the first 4 years after transplant. Previously, it was thought that immunosuppressant medications might act cumulatively and that these cancers would be more likely after many years of taking the drugs. Transplant patients must take immunosuppressant medications for the rest of their lives to prevent organ rejection.

The research team studied 139,991 non-Hispanic white transplant recipients in the Transplant Cancer Match Study. The study links the Scientific Registry of Transplant Recipients, which captures data on all transplants in the United States, with 15 population-based cancer registries, and includes information on almost half of the country's transplant population between 1987 and 2010. The researchers found 519 melanomas in this group and analyzed risk factors for developing melanoma.

Using a different data set, the researchers compared outcomes among 182 patients with melanoma in the transplant group with more than 130,000 other people with melanoma. Over 15 years, 27% of the transplant recipients died of their melanoma, as compared to 12% of the nonrecipients. The researchers found that melanoma patients who had received a transplant were three times more likely to die from their melanoma, even for melanomas that were diagnosed at an early stage or were very small.

The researchers found that the late-stage cases of melanoma were associated with use of medication given at the time of transplant that essentially stops T-cells, the main cells of immune response, from functioning in order to keep them from attacking the new organ.

Early stage melanomas were more likely to be found in recipients who were administered azathioprine, a maintenance drug given long term to some transplant recipients. This drug is known to multiply the effects of ultraviolet radiation, which could lead to the development of melanoma.

Robbins said her group's findings suggest that transplant candidates should be screened very carefully for skin cancers before receiving their transplant. She said it is possible that some of the melanomas could have been present at the time of transplant, but that immunosuppressive drugs allowed them to spread unchecked. She also said that closer monitoring after transplant could allow melanoma to be detected earlier, preventing patients from developing deadly metastatic cancer.

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