RANDOMIZED CLINICAL-TRIAL OF ANTITHYMOCYTE GLOBULIN INDUCTION IN RENAL-TRANSPLANTATION COMPARING A FIXED DAILY DOSE WITH DOSE ADJUSTMENT ACCORDING TO T-CELL MONITORING

Antithymocyte globulin (ATG) has been used successfully for induction therapy as well as for treatment of established allograft rejection. H owever, this therapy has often been associated with problems of overim munosuppression and increased costs. In a randomized clinical trial, w e compared the immunosuppressive benefits, complication rates, and tre atment costs when ATG is given as a fixed daily dose or when the dose is adjusted daily according to its biologic effects on T cells. Forty- five recipients of cadaver renal allografts were randomized into two g roups. In group 1 (n=23), ATG (ATGAM) was administered in variable dos es to maintain the absolute number of peripheral CD3 T cells at 50-100 /mu l. In group 2 (n=22), ATG was given at a fixed dose of 15 mg/kg/da y. Ah patients received azathioprine and prednisone. ATG was discontin ued at 7-14 days when cyclosporine was introduced. In both groups, CD2 , CD3, CD4, CD8, and CD19 cells were measured by flow cytometry and th e levels of cytokines IL-1 beta, IL-2R, ICAM-1, IL-6, IL-7, and IL-10 were measured by ELISA. In group 2, the levels of all T cell subsets w ere profoundly suppressed. In group 1, the number of CD3 and other T c ells was maintained at about 100 cells/mu l, while the CD19 T cells re mained unsuppressed. Cytokine levels were greatly suppressed in group 2 compared with group 1, except for IL-10 levels, which remained eleva ted in the latter group. Patient survival, graft function, and the inc idence of acute and recurrent rejections were similar in the two group s. Bone marrow suppression and infective complications were greater in group 2 than in group 1. The mean daily dose and the total quantity o f ATG used in group 1 were significantly smaller than in group 2, resu lting in a savings of $2,398.00 per patient per treatment. It is concl uded that monitoring of ATG by its biologic effects on T cells is a ra tional and safe method of regulating the dose of this important agent; in this way, it is possible to reduce the total amount of the drug gi ven to patients with consequent reduction in undesirable complications as well as in the cost of treatment without loss of immunosuppressive benefits.