Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation

Abstract

Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non-skin cancer (including melanoma) and skin cancer (excluding melanoma) for 481 patients during a median follow-up of 20.6 years. A total of 226 patients developed at least one cancer: 95 with non-skin cancer and 171 with skin cancer. In the intention-to-treat analysis, mean times to first non-skin cancer (16.0, 15.3, and 15.7 years for groups 1 through 3, respectively) and first skin cancer (13.6, 14.3, and 15.2 years, respectively) were not different among the three groups or between any subgroup. In multivariate analyses, non-skin cancer associated with increasing age and previous smoking history, whereas skin cancer associated with increasing age, nonbrown eye color, fairer skin, and a functioning transplant. Treatment allocation did not associate with development of either form of cancer in multivariate analyses. In conclusion, these immunosuppressive regimens, widely used in recent decades, carry similar risks for carcinogenicity after kidney transplantation.

Cancer in the Transplant Recipient

“…Those recipients experiencing acute rejection are treated by pulses of increased immunosuppression, thus increasing their immunosuppressive burden overall. It is possible that small differences of effect do exist among drugs, but that these are outweighed by the far greater effects of other known risk factors for cancer, such as age, sex, history of smoking, underlying disease leading to transplantation, and history of prior cancers (Webster et al 2007;Gallagher et al 2010). Given the large effect of these known risk factors and the need to balance long-term cancer risk against recipient and graft survival, any small differences among drugs are likely to be clinically unimportant.…”

“…However, differences among recipients taking cyclosporine versus those that are not has not resulted in differences in cancer in long-term trials (Gallagher et al 2010).…”

“…When used as a single agent to treat autoimmune diseases, azathioprine is associated with an increased riskof lymphomas and an increased risk of a wide range of solid neoplasms, including squamous cell carcinomas, urinary bladder tumors, breast carcinomas, and brain tumors. However, in organ transplant recipients, comparing immunosuppression regimens with and without Azathipoprine has not resulted in differences in cancer incidence (Gallagher et al 2010). Mycophenolate was originally developed as an anticancer drug, and acts through blockage of the purine biosynthesis, inhibiting inosine monophosphate dehydrogenase.…”

Malignant Neoplasms in Kidney Transplantation

“…Malignancy is a known complication among transplant recipients, and is likely to become even more common in these patients as donation criteria are extended to allow older donors, the age of patients on waiting list is increased, and transplant recipients live longer (Gallagher et al, 2010). However still there is a continuous struggle to keep the delicate balance between reducing the immunosuppression and maintaining the graft survival.…”

Piktybiniai Odos Navikai Recipientams Po Organų Transplantacijos

“…Odos karcinomos išsivystymui svarbus veiksnys yra ne tik bendras imunosupresinio gydymo intensyvumas [16,[35][36][37], bet ir skirtingos imunosupresinių vaistų savybės. Azatioprinas (antimetabolitas), veikdamas sinergistiškai su UV spinduliais, pasižymi mutageniniu poveikiu [38][39][40][41], kalcineurino inhibitoriai (pvz., ciklosporinas, takrolimuzas) skatina navikinių ląstelių invazyvumą ir angiogenezę [9,[42][43][44], be to, slopina DNR reparacijos mechanizmus [45].…”