A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection

E. Steve Woodle, J. Richard Thistlethwaite, John H. Gordon, David Laskow, Mark H. Deierhoi, James Burdick, John D. Pirsch, H. Sollinger, Flavio Vincenti, Lewis Burrows, Beth Schwartz, Gabriel M. Danovitch, Alan H. Wilkinson, David Shaffer, Mary Ann Simpson, Richard B. Freeman, Richard J. Rohrer, Robert Mendez, Saleh Aswad, Stephen R. Munn & 4 others Russell H. Wiesner, Frank L. Delmonico, John Neylan, John Whelchel

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Abstract

A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection. Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81%) had previously received at least one course of antilymphocyte antibody as rejection therapy. One-year follow-up was available in 93% of patients. Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78% of patients, stabilization in 11%, and progressive deterioration in 11%. The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine ≤3.0 mg/dl, 3%; 3.1-5 mg/dl, 16% (P<0.04); >5 mg/dl, 23% (P<0.02). Twelvemonth (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93% and 75%. Graft loss occurred in 19 patients (25%) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients(14%), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients. Antilymphocyte antibody therapy was not used to treat recurrent rejection. Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15%), including cytomegalovirus infection in three patients (4%). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0±9.9 ng/ml at day 7 of tacrolimus therapy and 9.4±5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18% of patients for rejection (11% for progressive, unrelenting rejection, and 7% for recurrent rejection). Tacrolimus therapy was discontinued in 8% of patients due to adverse events. In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good longterm renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection.

Original languageEnglish (US)
Pages (from-to)594-599
Number of pages6
JournalTransplantation
Volume62
Issue number5
StatePublished - Sep 15 1996

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Tacrolimus
Multicenter Studies
Allografts
Kidney
Therapeutics
Creatinine
Antilymphocyte Serum
Serum
Transplants
Safety
Lymphoproliferative Disorders
Cytomegalovirus Infections
Graft Survival
Nephrectomy
Adrenal Cortex Hormones
Survival Rate
Transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Woodle, E. S., Thistlethwaite, J. R., Gordon, J. H., Laskow, D., Deierhoi, M. H., Burdick, J., ... Whelchel, J. (1996). A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. Transplantation, 62(5), 594-599.

A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. / Woodle, E. Steve; Thistlethwaite, J. Richard; Gordon, John H.; Laskow, David; Deierhoi, Mark H.; Burdick, James; Pirsch, John D.; Sollinger, H.; Vincenti, Flavio; Burrows, Lewis; Schwartz, Beth; Danovitch, Gabriel M.; Wilkinson, Alan H.; Shaffer, David; Simpson, Mary Ann; Freeman, Richard B.; Rohrer, Richard J.; Mendez, Robert; Aswad, Saleh; Munn, Stephen R.; Wiesner, Russell H.; Delmonico, Frank L.; Neylan, John; Whelchel, John.

In: Transplantation, Vol. 62, No. 5, 15.09.1996, p. 594-599.

Research output: Contribution to journalArticle

Woodle, ES, Thistlethwaite, JR, Gordon, JH, Laskow, D, Deierhoi, MH, Burdick, J, Pirsch, JD, Sollinger, H, Vincenti, F, Burrows, L, Schwartz, B, Danovitch, GM, Wilkinson, AH, Shaffer, D, Simpson, MA, Freeman, RB, Rohrer, RJ, Mendez, R, Aswad, S, Munn, SR, Wiesner, RH, Delmonico, FL, Neylan, J & Whelchel, J 1996, 'A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection', Transplantation, vol. 62, no. 5, pp. 594-599.
Woodle ES, Thistlethwaite JR, Gordon JH, Laskow D, Deierhoi MH, Burdick J et al. A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. Transplantation. 1996 Sep 15;62(5):594-599.
Woodle, E. Steve ; Thistlethwaite, J. Richard ; Gordon, John H. ; Laskow, David ; Deierhoi, Mark H. ; Burdick, James ; Pirsch, John D. ; Sollinger, H. ; Vincenti, Flavio ; Burrows, Lewis ; Schwartz, Beth ; Danovitch, Gabriel M. ; Wilkinson, Alan H. ; Shaffer, David ; Simpson, Mary Ann ; Freeman, Richard B. ; Rohrer, Richard J. ; Mendez, Robert ; Aswad, Saleh ; Munn, Stephen R. ; Wiesner, Russell H. ; Delmonico, Frank L. ; Neylan, John ; Whelchel, John. / A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. In: Transplantation. 1996 ; Vol. 62, No. 5. pp. 594-599.
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abstract = "A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection. Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81{\%}) had previously received at least one course of antilymphocyte antibody as rejection therapy. One-year follow-up was available in 93{\%} of patients. Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78{\%} of patients, stabilization in 11{\%}, and progressive deterioration in 11{\%}. The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine ≤3.0 mg/dl, 3{\%}; 3.1-5 mg/dl, 16{\%} (P<0.04); >5 mg/dl, 23{\%} (P<0.02). Twelvemonth (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93{\%} and 75{\%}. Graft loss occurred in 19 patients (25{\%}) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients(14{\%}), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients. Antilymphocyte antibody therapy was not used to treat recurrent rejection. Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15{\%}), including cytomegalovirus infection in three patients (4{\%}). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0±9.9 ng/ml at day 7 of tacrolimus therapy and 9.4±5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18{\%} of patients for rejection (11{\%} for progressive, unrelenting rejection, and 7{\%} for recurrent rejection). Tacrolimus therapy was discontinued in 8{\%} of patients due to adverse events. In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good longterm renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection.",
author = "Woodle, {E. Steve} and Thistlethwaite, {J. Richard} and Gordon, {John H.} and David Laskow and Deierhoi, {Mark H.} and James Burdick and Pirsch, {John D.} and H. Sollinger and Flavio Vincenti and Lewis Burrows and Beth Schwartz and Danovitch, {Gabriel M.} and Wilkinson, {Alan H.} and David Shaffer and Simpson, {Mary Ann} and Freeman, {Richard B.} and Rohrer, {Richard J.} and Robert Mendez and Saleh Aswad and Munn, {Stephen R.} and Wiesner, {Russell H.} and Delmonico, {Frank L.} and John Neylan and John Whelchel",
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T1 - A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection

AU - Woodle, E. Steve

AU - Thistlethwaite, J. Richard

AU - Gordon, John H.

AU - Laskow, David

AU - Deierhoi, Mark H.

AU - Burdick, James

AU - Pirsch, John D.

AU - Sollinger, H.

AU - Vincenti, Flavio

AU - Burrows, Lewis

AU - Schwartz, Beth

AU - Danovitch, Gabriel M.

AU - Wilkinson, Alan H.

AU - Shaffer, David

AU - Simpson, Mary Ann

AU - Freeman, Richard B.

AU - Rohrer, Richard J.

AU - Mendez, Robert

AU - Aswad, Saleh

AU - Munn, Stephen R.

AU - Wiesner, Russell H.

AU - Delmonico, Frank L.

AU - Neylan, John

AU - Whelchel, John

PY - 1996/9/15

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N2 - A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection. Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81%) had previously received at least one course of antilymphocyte antibody as rejection therapy. One-year follow-up was available in 93% of patients. Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78% of patients, stabilization in 11%, and progressive deterioration in 11%. The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine ≤3.0 mg/dl, 3%; 3.1-5 mg/dl, 16% (P<0.04); >5 mg/dl, 23% (P<0.02). Twelvemonth (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93% and 75%. Graft loss occurred in 19 patients (25%) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients(14%), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients. Antilymphocyte antibody therapy was not used to treat recurrent rejection. Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15%), including cytomegalovirus infection in three patients (4%). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0±9.9 ng/ml at day 7 of tacrolimus therapy and 9.4±5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18% of patients for rejection (11% for progressive, unrelenting rejection, and 7% for recurrent rejection). Tacrolimus therapy was discontinued in 8% of patients due to adverse events. In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good longterm renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection.

AB - A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection. Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81%) had previously received at least one course of antilymphocyte antibody as rejection therapy. One-year follow-up was available in 93% of patients. Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78% of patients, stabilization in 11%, and progressive deterioration in 11%. The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine ≤3.0 mg/dl, 3%; 3.1-5 mg/dl, 16% (P<0.04); >5 mg/dl, 23% (P<0.02). Twelvemonth (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93% and 75%. Graft loss occurred in 19 patients (25%) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients(14%), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients. Antilymphocyte antibody therapy was not used to treat recurrent rejection. Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15%), including cytomegalovirus infection in three patients (4%). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0±9.9 ng/ml at day 7 of tacrolimus therapy and 9.4±5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18% of patients for rejection (11% for progressive, unrelenting rejection, and 7% for recurrent rejection). Tacrolimus therapy was discontinued in 8% of patients due to adverse events. In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good longterm renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection.

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