FK-506 RESCUE THERAPY FOR HEPATIC ALLOGRAFT-REJECTION - EXPERIENCE WITH AN AGGRESSIVE APPROACH

Although initial experiences with FK 506 rescue therapy for acute hepa tic allograft rejection have provided promising results, analysis of a vailable data indicates that inferior results are obtained when FK 506 rescue therapy is initiated in the latter stages of rejection. Since its initial availability, we have applied an aggressive approach towar ds FK 506 rescue therapy based on early conversion and assiduous dosin g. We have reviewed our experience with this approach in patients with refractory hepatic allograft rejection to provide an assessment of th is approach. Sixteen patients were treated for corticosteroid and OKT3 -resistant acute hepatic allograft rejection. Fourteen patients were t reated for cellular rejection and 2 for humorally-mediated rejection. Median follow-up was 7.3 months posttransplant and 6.0 months post-ini tiation of FK 506 therapy. Median time to first rejection was 8 days a nd median time to FK 506 therapy was 29 days. Laboratory values at the time of initiation of FK 506 therapy included: mean serum bilirubin, 4.0+/-3.1 mg/dl and SGPT 136+/-105 U/l. Prior to FK 506 therapy, patie nts received an average of 35.5+/-19.1 mg/kg of bolus/taper corticoste roids (prednisone equivalent) and 11.25+/-4.8 days of OKT3 therapy. FK 506 therapy was succesful in reversing all episodes of rejection. Med ian time to rejection reversal with FK 506 rescue therapy was 23 days (mean+/-SD, 27.6+/-16.7 days) in patients with cellular rejection. Tim e to rejection reversal was 26 and 28 days in the 2 patients with humo ral rejection. Patient and graft survival at 6 months were 100%/100%, and 94%/94% at 12 months. Graft loss to rejection was not observed. Si gnificant CMV infections occurred in 44% of patients: CMV hepatitis in 5 (31%), CMV pneumonitis in 1 patient (6%), and CMV viremia alone in 1 (6%). The mean time to CMV disease occurred on posttransplant day 29 , which corresponded to a median of 5 days of FK 506 therapy, suggesti ng that CMV disease was more probably the result of intense immunosupp ression which was administered prior to FK 506 therapy. These results indicate that an aggressive approach to FK 506 rescue therapy in patie nts with refractory hepatic allograft rejection: 1) provides high rate s of reversal, 2) provides excellent patient and graft-survival rates in a subset of patients at high risk for allograft loss, 3) appears to provide similar results for cellular and humorally-mediated hepatic a llograft rejection, and 4) allows for effective, simultaneous treatmen t of CMV disease and rejection. Continued attempts to reverse OKT3-res istant hepatic allograft rejection with conventional approaches (corti costeroids, repeat OKT3 therapy, polyclonal antilymphocyte preparation s) may no longer be warranted.