Lymphoproliferative disorders after renal transplantation in patients receiving triple or quadruple immunosuppression

A retrospective review of 478 renal transplant recipients receiving cyclosporin A (CsA) was conducted to determine the incidence, relative risk, and outcome of lymphoproliferative disease after transplantation. Cases of neoplasm were identified by linking the computerized databases of the British Columbia (B.C.) Transplant Society and the B.C. Cancer Agency. B.C. Cancer Statistics for 1988 were used to determine relative risk. Patients were monitored for a total of 1,054 patient years with a mean follow-up time of 26 months (range, 0.1 to 63 months). A total of 334 patients were treated with triple immunosuppression (CsA), azathioprine, and prednisone), and 144 received adjunctive antilymphocyte globulin as induction immunosuppression. Sixty-nine patients received OKT3 for the treatment of transplant rejection. Twenty-two patients developed 23 malignancies (4.8%) at a mean interval of 16 months (range, 3 to 45 months) after transplantation. Non-Hodgkins lymphoma occurred in five patients, of whom two received triple (0.6%) and three received quadruple (2.1%) therapy. All five patients, in addition, received OKT3 for the treatment of graft rejection. The relative risk of developing a neoplasm among the defined sample adjusted for age and sex was 3.08 overall, increasing to 26.9 (P less than 0.005) for lymphoma. Six of the 22 patients (27%), including all 5 patients with lymphoma, died as a result of their tumor. Renal transplant recipients receiving CsA have a significantly elevated risk of developing a de novo lymphoreticular malignancy, which is comparable to that reported for those receiving azathioprine treatment, and which appears to be increased by the use of quadruple immunosuppression and the administration of OKT3 for the treatment of acute graft rejection.