Controlled trial of azathioprine and cyclosporin to prevent anti-HLA antibodies due to third-party transfusion.

The beneficial effect of elective transfusion on renal allograft survival must be weighed against the risks of sensitisation. We report a randomised controlled trial in which patients in end-stage renal failure who were non-parous and not previously transplanted or transfused, were entered in a transfusion protocol during which one group received no drugs (controls), one received azathioprine, and one received cyclosporin. Each group was given three identical transfusions of leucocyte-enriched fresh blood at 2-3 week intervals. The transfused blood was of known HLA type and donor/recipient pairs were completely mismatched. Sensitisation rates were assessed by T and B cell cross-matches between donor and recipients and by the screening of all sera against lymphocytes from 40 random donors. Fifty-one patients have completed the protocol, 20 in the control group, 12 in the azathioprine group, and 19 in the cyclosporin group. The sensitisation rate in the control group was 30%, occasionally of high titre, and persistent. In the azathioprine group, 25% developed anti-HLA antibodies and reactivity was of high titre and was broadly specific. Sensitisation in the cyclosporin group was 10%, was narrowly specific, reacting with only 10% of a panel, and was transient. There was no difference in graft survival between the groups. We conclude that cyclosporin therapy concurrent with third-party transfusion reduces the incidence, titre, and duration of sensitisation.