FK506 (tacrolimus) compared with cyclosporine for primary immunosuppression after pediatric liver transplantation: Results from the U.S. multicenter trial

S. V. McDiarmid, R. W. Busuttil, N. L. Ascher, J. Burdick, Anthony M. D'Alessandro, C. Esquivel, M. Kalayoglu, A. S. Klein, J. W. Marsh, C. M. Miller, M. E. Schwartz, B. W. Shaw, S. K. So

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Abstract

We report on the efficacy and safety of FK506 (tacrolimus) compared with a cyclosporine (CsA)-based immunosuppressive regimen after 1 year of treatment in pediatric liver allograft recipients (< 12 years) participating in a multicenter U.S. randomized trial. Patients received either FK506 or CsA as primary immunosuppression following a first ABO-compatible liver transplant. Intravenous FK506 was initiated at 0.1 mg/kg per day, followed by oral FK506 beginning at 0.3 mg/kg per day. The dose was adjusted to maintain plasma trough levels of 0.5-2.0 ng/ml. The CsA group was treated according to each center’s usual protocol. Both groups received the same initial doses of corticosteroids. All rejection episodes were biopsy-proven and a standardized algorithm was adopted for the treatment of rejection. Thirty patients were randomized to the FK506 group and 20 to the CsA group. After twelve months of follow-up 20 patients remained in the FK506 group and 13 in the CsA group. Patient survivals were 80% and graft survival 70% in the FK506 group compared with 81% and 71% respectively, in the CsA group. 48% of the FK506 group remained rejection-free compared with 21% of the CsA group, and 79% of FK506-treated patients did not require OKT3 compared with 68% of CsA treated patients. The cumulative corticosteroid dose was less at each time point throughout the first year in the FK506 group. The incidence of serious and minor infections was similar in both groups. Nephrotoxicity, neurotoxicity, and gastrointestinal disturbances were the major tox-icities reported. Differences did not reach statistical significance between the two groups although major neurologic events, diarrhea and dyspepsia were more often reported in the FK506 group. There was no difference in mean serum creatinine at 12 months between the two groups. There was a tendency toward lower mean serum cholesterol in the FK506 group. There was no hirsuitism in the FK506 group compared with a 30% incidence in the CsA group. In conclusion, compared with CsA, there is a trend toward less rejection in FK506-treated pediatric allograft recipients, while both drugs have a similar spectrum of side effects.

Original languageEnglish (US)
Pages (from-to)530-536
Number of pages7
JournalTransplantation
Volume59
Issue number4
DOIs
StatePublished - Feb 27 1995

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Tacrolimus
Liver Transplantation
Immunosuppression
Cyclosporine
Multicenter Studies
Pediatrics
Allografts
Adrenal Cortex Hormones
Muromonab-CD3
Dyspepsia
Liver
Incidence
Graft Survival
Immunosuppressive Agents
Serum
Nervous System
Diarrhea
Creatinine

ASJC Scopus subject areas

  • Transplantation

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FK506 (tacrolimus) compared with cyclosporine for primary immunosuppression after pediatric liver transplantation : Results from the U.S. multicenter trial. / McDiarmid, S. V.; Busuttil, R. W.; Ascher, N. L.; Burdick, J.; D'Alessandro, Anthony M.; Esquivel, C.; Kalayoglu, M.; Klein, A. S.; Marsh, J. W.; Miller, C. M.; Schwartz, M. E.; Shaw, B. W.; So, S. K.

In: Transplantation, Vol. 59, No. 4, 27.02.1995, p. 530-536.

Research output: Contribution to journalArticle

McDiarmid, SV, Busuttil, RW, Ascher, NL, Burdick, J, D'Alessandro, AM, Esquivel, C, Kalayoglu, M, Klein, AS, Marsh, JW, Miller, CM, Schwartz, ME, Shaw, BW & So, SK 1995, 'FK506 (tacrolimus) compared with cyclosporine for primary immunosuppression after pediatric liver transplantation: Results from the U.S. multicenter trial', Transplantation, vol. 59, no. 4, pp. 530-536. https://doi.org/10.1097/00007890-199559040-00016
McDiarmid, S. V. ; Busuttil, R. W. ; Ascher, N. L. ; Burdick, J. ; D'Alessandro, Anthony M. ; Esquivel, C. ; Kalayoglu, M. ; Klein, A. S. ; Marsh, J. W. ; Miller, C. M. ; Schwartz, M. E. ; Shaw, B. W. ; So, S. K. / FK506 (tacrolimus) compared with cyclosporine for primary immunosuppression after pediatric liver transplantation : Results from the U.S. multicenter trial. In: Transplantation. 1995 ; Vol. 59, No. 4. pp. 530-536.
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abstract = "We report on the efficacy and safety of FK506 (tacrolimus) compared with a cyclosporine (CsA)-based immunosuppressive regimen after 1 year of treatment in pediatric liver allograft recipients (< 12 years) participating in a multicenter U.S. randomized trial. Patients received either FK506 or CsA as primary immunosuppression following a first ABO-compatible liver transplant. Intravenous FK506 was initiated at 0.1 mg/kg per day, followed by oral FK506 beginning at 0.3 mg/kg per day. The dose was adjusted to maintain plasma trough levels of 0.5-2.0 ng/ml. The CsA group was treated according to each center’s usual protocol. Both groups received the same initial doses of corticosteroids. All rejection episodes were biopsy-proven and a standardized algorithm was adopted for the treatment of rejection. Thirty patients were randomized to the FK506 group and 20 to the CsA group. After twelve months of follow-up 20 patients remained in the FK506 group and 13 in the CsA group. Patient survivals were 80{\%} and graft survival 70{\%} in the FK506 group compared with 81{\%} and 71{\%} respectively, in the CsA group. 48{\%} of the FK506 group remained rejection-free compared with 21{\%} of the CsA group, and 79{\%} of FK506-treated patients did not require OKT3 compared with 68{\%} of CsA treated patients. The cumulative corticosteroid dose was less at each time point throughout the first year in the FK506 group. The incidence of serious and minor infections was similar in both groups. Nephrotoxicity, neurotoxicity, and gastrointestinal disturbances were the major tox-icities reported. Differences did not reach statistical significance between the two groups although major neurologic events, diarrhea and dyspepsia were more often reported in the FK506 group. There was no difference in mean serum creatinine at 12 months between the two groups. There was a tendency toward lower mean serum cholesterol in the FK506 group. There was no hirsuitism in the FK506 group compared with a 30{\%} incidence in the CsA group. In conclusion, compared with CsA, there is a trend toward less rejection in FK506-treated pediatric allograft recipients, while both drugs have a similar spectrum of side effects.",
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AU - Ascher, N. L.

AU - Burdick, J.

AU - D'Alessandro, Anthony M.

AU - Esquivel, C.

AU - Kalayoglu, M.

AU - Klein, A. S.

AU - Marsh, J. W.

AU - Miller, C. M.

AU - Schwartz, M. E.

AU - Shaw, B. W.

AU - So, S. K.

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N2 - We report on the efficacy and safety of FK506 (tacrolimus) compared with a cyclosporine (CsA)-based immunosuppressive regimen after 1 year of treatment in pediatric liver allograft recipients (< 12 years) participating in a multicenter U.S. randomized trial. Patients received either FK506 or CsA as primary immunosuppression following a first ABO-compatible liver transplant. Intravenous FK506 was initiated at 0.1 mg/kg per day, followed by oral FK506 beginning at 0.3 mg/kg per day. The dose was adjusted to maintain plasma trough levels of 0.5-2.0 ng/ml. The CsA group was treated according to each center’s usual protocol. Both groups received the same initial doses of corticosteroids. All rejection episodes were biopsy-proven and a standardized algorithm was adopted for the treatment of rejection. Thirty patients were randomized to the FK506 group and 20 to the CsA group. After twelve months of follow-up 20 patients remained in the FK506 group and 13 in the CsA group. Patient survivals were 80% and graft survival 70% in the FK506 group compared with 81% and 71% respectively, in the CsA group. 48% of the FK506 group remained rejection-free compared with 21% of the CsA group, and 79% of FK506-treated patients did not require OKT3 compared with 68% of CsA treated patients. The cumulative corticosteroid dose was less at each time point throughout the first year in the FK506 group. The incidence of serious and minor infections was similar in both groups. Nephrotoxicity, neurotoxicity, and gastrointestinal disturbances were the major tox-icities reported. Differences did not reach statistical significance between the two groups although major neurologic events, diarrhea and dyspepsia were more often reported in the FK506 group. There was no difference in mean serum creatinine at 12 months between the two groups. There was a tendency toward lower mean serum cholesterol in the FK506 group. There was no hirsuitism in the FK506 group compared with a 30% incidence in the CsA group. In conclusion, compared with CsA, there is a trend toward less rejection in FK506-treated pediatric allograft recipients, while both drugs have a similar spectrum of side effects.

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