Neoplastic disease after heart transplantation: single centre experience

OBJECTIVES: Mandatory use of prolonged immunosuppression in organ transplantation is complicated by an increased incidence of cancer. The current study represents a retrospective analysis of the incidence of neoplasms in our heart transplantation program.

METHODS: Four-hundred and seventy-four patients (403 male and 71 female; mean age, 48.6+/-12.1 years), with at least 30 days of follow-up, were enrolled in this study. Patients received triple immunosuppression with cyclosporin A, azathioprine and steroids. Moreover, as a prophylactic anti-lymphocyte therapy, 388 patients (82%) were administered RATG, 67 patients (14%) received ALG and 19 patients (4%) OKT3. The mean follow-up time was 71.1+/-43.0 months.

RESULTS: Fifty-five patients (11.6%) developed malignant neoplasms. The cancer frequencies were: solid tumors, 55%; non-Hodgkin lymphomas (NHL), 20%; Kaposi's sarcomas, 11%; skin cancers, 9%; undifferentiated sarcomas and myelomas, 5%. Solid tumors mainly affected the lung (39%), bowel (16%), stomach (6.5%), liver (6.5%), pancreas (6.5%) and oral cavity (6.5%). The times to the onset of cancer from transplantation were: Kaposi's sarcoma, 12.7+/-16.8 months; skin cancers, 34.5+/-23.8 months; solid tumors, 54.3+/-38.7 months; NHL, 60.1+/-36.4 months; undifferentiated sarcomas and myelomas, 90.0+/-15.6 months. As determined by univariate and multivariate analyses, sex, number of treated rejections, previous history of tumor, average dose of cyclosporine and prednisone and cyclosporine blood levels did not increase the incidence of malignancies. Univariate analysis suggests a significant correlation between the type of prophylactic immunoglobulins and the average dose of azathioprine with the incidence of neoplasms. Both univariate and multivariate analyses demonstrated a significant correlation between patient's age at the time of transplantation and risk of cancer occurrence (risk increased by 1.074/year; P=0.0056 with multivariate Cox regression).

CONCLUSIONS: Cancer is a strong limitation for long-term survival after heart transplantation. The only risk factor recognized is the patient's age at the time of transplant. Furthermore, the type of prophylactic globulins used for induction therapy and some specific immunosuppressant agent (azathioprine) may play a significant role in the development of malignancies after transplantation.