Choice of Calcineurin Inhibitor and Development of New Malignancies in Liver Transplant Recipients

Abstract

Purpose: The goal was to examine whether the choice of calcineurin inhibitor is associated with the development of new malignancies in liver transplant patients. We also examined demographic and clinical variables associated with new malignancy development. Methods: Data was obtained from The United Network for Organ Sharing (UNOS) on all liver transplants done from 1987–2005. To be included, patients must: 1) have been transplanted from 1995–2005, 2) be ≥ 18 years old at the time of transplant, 3) not have a history of malignancy or be found to have malignancy at the time of transplant, 4) not have received an organ from a donor with a history of malignancy, 5) have been discharged from the hospital on either cyclosporine (CSA) or tacrolimus, and 6) not have been diagnosed with a “new” malignancy within the first 6 months post-transplant. Unadjusted hazard rates (HR) for each variable were obtained by entering them individually into a Cox proportional hazards (CPH) model. Statistically significant variables, as well as basic demographic variables, were then used to build a multivariate CPH model. Results: 37,331 patients met criteria for inclusion. 24,433 (65%) were on tacrolimus and 12,898 (35%) were on CSA at discharge. There were 1,392 (3.7%) new malignancies (934 in the tacrolimus group and 458 in the CSA group). The most common non-cutaneous malignancies were non-Hodgkin's lymphoma (171 cases), lung cancer (158 cases), and colorectal cancer (51 cases). After multivariate adjustment, there was no statistically significant difference in the hazard rate for developing a new malignancy for tacrolimus compared to CSA (HR 0.96, 95% CI: 0.84–1.09). Older age, male gender, and Caucasian race were independently associated with an increased hazard rate of malignancy. Clinical factors independently associated with a statistically significantly increased hazard rate for malignancy included alcohol-induced liver disease (HR 1.28, 95% CI: 1.13–1.46) or primary sclerosing cholangitis (HR 1.42, 95% CI: 1.20–1.68), and use of mycophenolate mofetil (HR 1.15, 95% CI: 1.02–1.29). Conclusions: There is no significant difference in the hazard rate for developing a post-transplant malignancy among liver transplant patients receiving either a tacrolimus or CSA-based immunosuppressant regimen. After controlling for demographic variables, transplantation for alcohol-induced liver disease or primary sclerosing cholangitis and use of mycophenolate mofetil are associated with an increased hazard for new malignancy.