EFFECT OF LONG-TERM IMMUNOSUPPRESSION IN KIDNEY-GRAFT RECIPIENTS ON CANCER INCIDENCE - RANDOMIZED COMPARISON OF 2 CYCLOSPORINE REGIMENS

Background Long-term administration of cyclosporin carries a risk of r enal toxicity, and immunosuppressants are associated with an increased rate of malignant disorders. We undertook an open randomised study of the risks and benefits of two long-term maintenance regimens of cyclo sporin in kidney-allograft recipients. The primary endpoint was graft function; secondary endpoints were survival and occurrence of cancer a nd rejection. Methods 231 recipients of a first allograft with at most one previous rejection episode were randomised 1 year after transplan tation. Most were receiving cyclosporin and azathioprine. One group re ceived cyclosporin doses adjusted to yield trough blood concentrations of 75-125 ng/mL (low-dose group); the second received doses that yiel ded trough concentrations of 150-250 ng/mL (normal-dose group). Analys is was by intention to treat. Findings At 66 months' follow-up, the lo w-dose and normal-dose groups were similar in mean serum creatinine (1 82 [SD 160] vs 184 [157] mu mol/L; p=0.9) and mean creatinine clearanc e (47.5 [25.1] vs 45.3 (22.5] mL/min; p=0.6). Nine of 116 patients in the low-dose group and one of 115 in the normal-dose group had symptom s of rejection (p<0.02). There was no difference between the low-dose and normal-dose groups in survival (95 vs 92%; p=0.7) or graft surviva l (89 vs 82%; p=0.17) at 6 years. 60 patients developed cancers, 37 in the normal-dose group and 23 in the row-dose group (p<0.034); 66% wer e skin cancers (26 vs 17; p<0.05). Interpretation We found no evidence that halving of trough blood cyclosporin concentrations significantly changes graft function or graft survival. The low-dose regimen was as sociated with fewer malignant disorders but more frequent rejection. T he design of long-term maintenance protocols for transplant recipients based on powerful immunosuppressant combinations should take these po tential risks into account.