Organ transplant recipients regularly receive immunosuppressive drugs to help minimize the risk of rejection, but those drugs come with significant risks of their own, including leaving patients open to predatory infections and even certain types of cancer.
Now, a new study suggests the type of immunosuppressant drug used as well as other factors may help predict those risks and possibly reduce them. The study was presented at the 2014 World Transplant Congress in San Francisco by lead researcher Dr. Sebastian Rademacher, a surgeon at the Campus Virchow Clinic in Charité, Berlin.
Conducted by researchers in Germany, the study evaluated 1,179 adult patients who underwent liver transplantation procedures between 1988 and 2002, and then they were followed through 2013. The average patient age at the time of transplant was 47 years old, and the average follow-up time was just under 14 years.
The study examined several factors, including age and immunosuppressant therapy, to determine potential risk factors. For comparison, the researchers relied on sex- and age-matched men and women from the general German population.
"The development of de novo malignancies after liver transplantation is one of the leading causes of late mortality in liver transplant recipients," the researchers wrote in the study.
Data used in the study comprised nearly 30 unique treatment regimens, focusing on immunosuppressive therapies given for at least two years. Steroid-free regimens and low-dose steroids were not included in the evaluation, nor were those using mTOR (mammalian target of rapamycin) inhibitors since they were introduced too late in the study period to make a fair and critical evaluation possible.
For the research, de novo malignancies were divided into three categories: post-transplant lymphoproliferative disorder, skin cancer and nonskin solid organ tumors. After analyzing the data, the researchers found the probability of developing any de novo malignancy increased significantly over time, from 2.5 percent at five years to 22 percent at 20 years post-transplant.
Regarding the development of nonskin solid tumors specifically, the researchers noted a risk of 4.8 percent at five years, growing to 14.4 percent at 20 years after initial transplant surgery. The mean age of any cancer diagnosis was 56 years.
Cancers noted in study subjects included breast cancer, cancers of the larynx and oropharynx, colon and rectal cancers, lung cancer, stomach and esophageal cancers, kidney and bladder cancers and uterine and ovarian cancers.
After multivariate analysis, the researchers found the risk of developing a solid-organ cancer was significantly reduced among patients who received tacrolimus compared to those who received cyclosporine A. Those who smoked were also at greater risk for developing the tumors compared to patients who were never smokers.
The underlying cause for transplant also played a role in determining long-term risk for solid organ tumors, with a reduced risk associated with patients whose initial pretransplant diagnosis included primary biliary cirrhosis, primary sclerosing cholangitis or hepatitis C infection.
Rejection frequency, which is commonly used as a surrogate marker for immunosuppression, did not play a significant role in predicting the development of solid tumors.
Rademacher told conference attendees the study's results demonstrate the need to "reoptimize" immunosuppressive regimens to potentially help reduce the long-term risk of post-transplant cancers, especially among high-risk patients. Additional studies of surrogate markers and surveillance protocol are needed to refine therapy recommendations, he said.
