Increased cancer risk for kidney transplant recipients linked to Epstein-Barr virus

PHILADELPHIA— More than 90% of the adult population in the U.S. is or has been infected with Epstein Barr virus (EBV). EBV is a highly contagious member of the herpes virus family, best known for causing infectious mononucleosis (“mono”) and for its association with several cancers and autoimmune diseases. Kidney transplant patients who’ve never been exposed to EBV but receive organs from a donor who carried the virus may develop a life-threatening post-transplant complication called lymphoproliferative disorder (PTLD), according to a new study from the Perelman School of Medicine at the University of Pennsylvania. An estimated 4 to 5 percent of adult kidney transplants – as many as 1200 patients per year – could be at risk of the condition, in which the body’s immune system gets confused and immune cells can grow out of control and act like cancer. The findings were recently published in Annals of Internal Medicine.

In kidney transplant recipients who had not previously been infected with EBV, researchers found that 22 percent who received a kidney from a donor who previously was infected with EBV developed PTLD – a rare and aggressive form of cancer — within three years post-transplant. That cancer rate is five to ten times higher than previously estimated for kidney recipients, based on national registry data. Additionally, recipients who did not have EBV and received kidneys from people who did have a prior exposure to EBV faced a higher risk of death; nearly one-third of those affected by PTLD passed away from it during the study period.

This research adds significantly to the overall understanding of the disease. While the risk of being diagnosed with PTLD following a kidney transplant is widely recognized, it has historically been studied in populations of children since the chances of adults having zero exposure to EBV is much lower compared to children.

“National registry data likely underestimates PTLD incidence due to incomplete reporting and errors in tracking whether organ donors and recipients have been exposed to viruses like EBV,” said the study’s lead author, Vishnu Potluri, MD, MPH, an assistant professor in the Renal Electrolyte and Hypertension Division at Penn. “Our research used comprehensive, high-quality data from two leading U.S. transplant centers, and revealed a much higher risk than previous data has suggested.”

Implications for patient care

Emily Blumberg, MD, Penn’s director of Transplant Infectious Diseases, emphasizes the importance of proactive strategies for patient care, “We need to rethink how we monitor patients for EBV infection and how we manage immunosuppression for these high-risk patients. This includes early and routine testing for EBV activity in the blood and exploring personalized adjustments to immunosuppressive therapy.”

“Given the significant threat to survival posed by PTLD and the substantial discrepancy between our findings and prior data, our study serves as a call to action to prioritize further research to enhance the safety and survival of this vulnerable transplant population,” said Chethan Puttarajappa, MBBS, MS, an associate professor in the renal-electrolyte division at the University of Pittsburgh and senior author of the study.

Funding for the study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases (K08DK127250, K08DK119576, R01-DK070869), the National Institute of Allergy and Infectious Diseases (K24AI146137), and the University of Pennsylvania McCabe Fund.

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

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