Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: Analysis of the transplant registry of the International Society for Heart and Lung Transplantation

Background: Malignancy after organ transplantation has been described as the price of immunotherapy. Evolving strategies aimed at effective immunosuppression could have differing effects on the likelihood of developing malignancy. We analyzed data from the transplant registry of the International Society for Heart and Lung Transplantation (ISHLT) to ascertain which factors are associated with the development of malignancy after orthotopic heart transplantation (OHT). Methods: Multivariate modeling was performed to determine factors predictive of first post-transplant malignancy in patients taking standard immunosuppressive regimens, defined as cyclosporine or tacrolimus and azathioprine or mycophenolate mofetil (MMF), who underwent OHT between January 1, 1995 and December 31, 1997. Results: Of the 3,895 transplants described in the cohort, 703 (18%) developed post-transplant malignancy at any time during the follow-up period, and 549 (14%) developed malignancy within the first 5 years post-transplant. The breakdown of malignancy was as follows: skin: 47%; post-transplant lymphoproliferative disease: 10%; other malignancies: 24%; combination of types: 10%; and unreported: 10%. Multivariate modeling revealed that independent predictors of increased risk were prior malignancy and increased age, whereas the use of MMF as part of a standard immunosuppressive regimen was associated with an adjusted relative risk (RR) = 0.73 (95% confidence interval 0.56 to 0.95). Relative to a recipient age of 55 years, the risk of malignancy for 30, 45 and 60 years of age was 0.32, 0.46 and 1.37, respectively. Although the use of tacrolimus appeared protective in the univariate analysis, it was not significant according to multivariate analysis. Female gender appeared to be protective. Neither OKT3 nor antithymocyte globulin (ATG) use was associated with a significantly increased risk of malignancy. Conclusions: The choice of inummosuppressive regimen may affect the likelihood of developing malignancy after OHT. Induction immunosuppression does not appear to increase the risk of subsequent malignancy. The use of MMF in standard immunosuppressive regimens is associated with a significantly lower risk of developing malignancy.