Long-term outcome of the use of OKT3 to treat steroid-resistant acute renal allograft rejection
Transplant International - 1994
Tóm tắt
OKT3 was used to treat steroid-resistant acute renal allograft refection in 30 of 496 adult patients transplanted over a 6-year period. Rejection was reversed (defined as a fall in serum creatinine by 50% or more within 30 days of treatment with OKT3) in 40% of cases. Successful reversal was significantly more likely when rejection occurred shortly after transplantation (t ratio-2.53; P=0.019). The long-term outcome was disappointing; the actuarial graft survival at 1 year from the start of treatment with OKT3 was 42%, and no grafts have thus far survived longer than 3 years. Graft survival was horter in older patients (coefficient/standard error 2.226; P<0.05), and no other predictor of long-term outcome was identified. Patient survival at 3 years was 88%. Serious infection occurred in 33% of patients, with two deaths. Our experience suggests that treatment with OKT3 is unlikely to reverse acute renal allograft rejection in more than half of patients where rejection is resistant to steroids. Although long-term graft survival occurred in a few cases, the overall long-term outcome was disappointing, particularly in older patients. Finally, our analysis indicates the difficulty of predicting which patients will derive long-term benefit when OKT3 is used to treat steroidresistant rejection.
Từ khóa
Tài liệu tham khảo
Chatenoud L, Ferran C, Reuter A, Legendre C, Gevaert Y, Kreis H, Franchimont P, Bach JF (1989) Systemic reaction to the anti-T-cell monoclonal antibody OKT3 in relation to serum levels of tumor necrosis factor and interferonalpha. N Engl J Med 320: 1420–1421
Chatenoud L, Legendre C, Ferran C, Bach JF, Kreis H (1991) Corticosteroids inhibition of the OKT3 induced cytokine related syndrome: dosage and kinetics prerequisites. Transplantation 51:334–338
D'Alessandro AM, Pirsch JD, Stratta RJ, Sollinger HW, Kalayoglu M, Maki DG, Belzer FO (1989) OKT3 salvage therapy in a quadruple immunosuppressive protocol in cadaveric renal transplantation. Transplantation 47: 297–300
Davies SP, Brown EA, Woodrow DF, Phillips ME, Gower PE, Mee AD (1991) The high failure rate of OKT3 in the treatment of acute renal allograft rejection resistant to steroids with or without antithymocyte globulin. Transplantation 52:746–749
Deierhoi MH, Barber WH, Curtis JJ, Julian BA, Luke RG, Hudson S, Barger BO, Diethelm AG (1988) A comparison of OKT3 monoclonal antibody and corticosteroids in the treatment of acute renal allograft rejection. Am J Kidney Dis 21: 86–89
Goldman M, Van Laethem JL, Abramowicz D, De Pauw L, Kinnaert P, Vereerstraeten P (1990) Evolution of renal function during the treatment of kidney graft rejection with OKT3 monoclonal antibody. Transplantation 50: 158–159
Hirsch RL, Layton PC, Barnes LA, Kremer AB, Goldstein G (1987) Orthoclone OKT3 treatment of acute renal allograft rejection in patients receiving maintenance cyclosporine therapy. Transplant Proc 19 [Suppl 1]: 32–36
Hrirck DE, Mayes JT, Schulak JA (1990) Inhibition of anti-OKT3 antibody generation by cyclosporin. Results of a prospective randomised trial. transplantation 50: 237–240
Kreis H, Legendre C, Chatenoud L (1991) OKT3 in organ transplantation. Transplant Rev 5: 181–199
Monaco A, Goldstein G, Barnes L (1987) Use of Orthoclone OKT3 monoclonal antibody to reverse renal allograft rejection unresponsive to treatment with conventional immunosuppressive regimens. Transplant Proc 19 [Suppl 1]: 28–31
Norman DJ, Shield CF, Barry J, Henell K, Funnell MB, Lemon J (1987) A U. S. clinical study of Orthoclone OKT3 in renal transplantation. Transplant Proc 19: 21–27
Norman DJ, Barry JM, Bennett WM, Leone M, Henell K, Funnell B, Hubert B (1988) The use of OKT3 in cadaveric renal transplantation for rejection that is unresponsive to conventional anti-rejection therapy. Am J Kidney Dis 21: 90–93
Oh C-S, Sollinger HW, Stratta RJ, Kalayoglu M, Belzer FO (1988) Delayed response to Orthoclone OKT3 treatment for renal allograft rejection resistant to steroid and antilymphocyte globulin. Transplantation 45: 65–67
Ortho Mulitcentre Tansplant Study Group (1985) A randomised clincial trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplant. N Engl J Med 313: 337–342
Ponticelli C, Rivolta E, Tarantino A, Egidi F, Banfi G, De Vecchi A, Montagnino G, Vegeto A (1986) Clinical experience with Orthoclone OKT3 in renal transplantation. Transplant Proc 18: 942–948
Rowe PA, Rocker GM, Morgan AG, Shale DJ (1987) OKT3 and pulmonary capillary permeability. BMJ 295: 1099–1100
Rowe PA, McGregor EM, Watson MA, Macpherson SG (1991) Results of an audit of living related allograft donation from a single centre. In: Land W, Dossetor JB (eds) Ethics, justice and commerce in organ replacement therapy, Springer, Berlin, pp 60–63
Schroeder TJ, Weiss MA, Smith RD, Stephens GW, First MR (1991) The efficacy of OKT3 in vascular rejection. Transplantation 51: 312–315
Swinnen LJ, Costanzo-Nordin MR, Fisher SG, O'Sullivan EJ, Johnson MR, Heroux AL, Dizikes GJ, Pifarre R, Fisher RI (1990) Increased incidence of lymphoproliferative disorders after immunosuppression with the monoclonal antibody OKT3 in cardiac transplant recipients. N Engl J Med 323: 1723–1728
Thistlethwaite JR, Gaber AO, Haag BW, Aronson AJ, Broelsch CE, Stuart JK, Stuart FP (1987) OKT3 treatment of steroid resistant renal allograft rejection. Transplantation 43: 176–183