FK 506 rescue therapy for hepatic allograft rejection: Experience with an aggressive approach

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Abstract
Although initial experiences with FK 506 rescue therapy for acute hepatic allograft rejection have provided promising results, analysis of available 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 towards FK 506 rescue therapy based on early conversion and assiduous dosing. We have reviewed our experience with this approach in patients with refractory hepatic allograft rejection to provide an assessment of this approach. Sixteen patients were treated for corticosteroid and OKT3‐resistant acute hepatic allograft rejection. Fourteen patients were treated for cellular rejection and 2 for humorally‐mediated rejection. Median followup was 7.3 months posttransplant and 6.0 months post‐initiation of FK 506 therapy. Median time to first rejection was 8 days and 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 Ul. Prior to FK 506 therapy, patients received an average. of 35.5±19.1 mg/kg of bolus/taper corticosteroids (prednisone equivalent) and 11.25±4.8 days of OKT3 therapy. FK 506 therapy was succesful in reversing all episodes of rejection. Median time to rejection reversal with FK 506 rescue therapy was 23 days (mean±SD, 27.6±16.7 days) in patients with cellular rejection. Time to rejection reversal was 26 and 28 days in the 2 patients with humoral rejection. Patient and graft survival at 6 months were 100%/100%, and 94%94% at 12 months. Graft loss to rejection was not observed. Significant 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, suggesting that CMV disease was more probably the result of intense immunosuppression which was administered prior to FK 506 therapy. These results indicate that an aggressive approach to FK 506 rescue therapy in patients with refractory hepatic allograft rejection: 1) provides high rates 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 allograft rejection, and 4) allows for effective, simultaneous treatment of CMV disease and rejection. Continued attempts. to reverse OKT3‐resistant hepatic allograft rejection with conventional approaches (corticosteroids, repeat OKT3 therapy, polyclonal antilymphocyte preparations) may no longer be warranted.

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