A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation

Rainer W G Gruessner, George W. Burke, Robert Stratta, Hans Sollinger, Enrico Benedetti, Christopher Marsh, Peter Stock, J. Philip Boudreaux, Maureen Martin, Mary Beth Drangstveit, David E R Sutherland, Angelika C Gruessner

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113 Citations (Scopus)

Abstract

Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n=82), (2) recipients switched to FK506 for antirejection or rescue therapy (n=61), and (3) recipients converted to FK506 for other reasons (n=11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% ≥2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P=0.04); for PTA recipients, 84% versus 66% (P=n.s.); and for PAK recipients, 80% versus 14% (P=0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV- positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P=n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.

Original languageEnglish (US)
Pages (from-to)261-273
Number of pages13
JournalTransplantation
Volume61
Issue number2
DOIs
StatePublished - Jan 27 1996
Externally publishedYes

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Pancreas Transplantation
Tacrolimus
Pancreas
Transplants
Therapeutics
Cyclosporine
Graft Survival
Lymphoma
Bone Marrow
Azathioprine
Prednisone
Immunosuppression
Survival Rate
Insulin
Kidney
Matched-Pair Analysis

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation. / Gruessner, Rainer W G; Burke, George W.; Stratta, Robert; Sollinger, Hans; Benedetti, Enrico; Marsh, Christopher; Stock, Peter; Boudreaux, J. Philip; Martin, Maureen; Drangstveit, Mary Beth; Sutherland, David E R; Gruessner, Angelika C.

In: Transplantation, Vol. 61, No. 2, 27.01.1996, p. 261-273.

Research output: Contribution to journalArticle

Gruessner, RWG, Burke, GW, Stratta, R, Sollinger, H, Benedetti, E, Marsh, C, Stock, P, Boudreaux, JP, Martin, M, Drangstveit, MB, Sutherland, DER & Gruessner, AC 1996, 'A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation', Transplantation, vol. 61, no. 2, pp. 261-273. https://doi.org/10.1097/00007890-199601270-00018
Gruessner, Rainer W G ; Burke, George W. ; Stratta, Robert ; Sollinger, Hans ; Benedetti, Enrico ; Marsh, Christopher ; Stock, Peter ; Boudreaux, J. Philip ; Martin, Maureen ; Drangstveit, Mary Beth ; Sutherland, David E R ; Gruessner, Angelika C. / A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation. In: Transplantation. 1996 ; Vol. 61, No. 2. pp. 261-273.
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title = "A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation",
abstract = "Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n=82), (2) recipients switched to FK506 for antirejection or rescue therapy (n=61), and (3) recipients converted to FK506 for other reasons (n=11). Of 82 patients in the induction group, 7 (9{\%}) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66{\%}) had SPK transplants without BM, 14 (17{\%}) had pancreas transplants alone (PTA), and 7 (9{\%}) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16{\%}), nephrotoxicity (13{\%}), and gastrointestinal toxicity (9{\%}). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72{\%}) were SPK, 11 (18{\%}) PTA, and 6 (10{\%}) PAK. All but 3 (95{\%}) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46{\%} of the recipients had one, and 54{\%} ≥2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25{\%}), neurotoxicity (23{\%}), and gastrointestinal toxicity (21{\%}). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90{\%} for SPK, 100{\%} for PTA, and 100{\%} for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87{\%} for FK506 versus 70{\%} for cyclosporine recipients (P=0.04); for PTA recipients, 84{\%} versus 66{\%} (P=n.s.); and for PAK recipients, 80{\%} versus 14{\%} (P=0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35{\%} for SPK, 40{\%} for PTA, and 20{\%} for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV- positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91{\%} for SPK, 100{\%} for PTA, and 80{\%} for PAK (P=n.s.). Pancreas graft survival rates at 6 months were 90{\%} for SPK, 72{\%} for PTA, and 40{\%} for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44{\%} in SPK, 54{\%} in PTA, and 50{\%} in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.",
author = "Gruessner, {Rainer W G} and Burke, {George W.} and Robert Stratta and Hans Sollinger and Enrico Benedetti and Christopher Marsh and Peter Stock and Boudreaux, {J. Philip} and Maureen Martin and Drangstveit, {Mary Beth} and Sutherland, {David E R} and Gruessner, {Angelika C}",
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T1 - A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation

AU - Gruessner, Rainer W G

AU - Burke, George W.

AU - Stratta, Robert

AU - Sollinger, Hans

AU - Benedetti, Enrico

AU - Marsh, Christopher

AU - Stock, Peter

AU - Boudreaux, J. Philip

AU - Martin, Maureen

AU - Drangstveit, Mary Beth

AU - Sutherland, David E R

AU - Gruessner, Angelika C

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N2 - Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n=82), (2) recipients switched to FK506 for antirejection or rescue therapy (n=61), and (3) recipients converted to FK506 for other reasons (n=11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% ≥2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P=0.04); for PTA recipients, 84% versus 66% (P=n.s.); and for PAK recipients, 80% versus 14% (P=0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV- positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P=n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.

AB - Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n=82), (2) recipients switched to FK506 for antirejection or rescue therapy (n=61), and (3) recipients converted to FK506 for other reasons (n=11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% ≥2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P=0.04); for PTA recipients, 84% versus 66% (P=n.s.); and for PAK recipients, 80% versus 14% (P=0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV- positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P=n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.

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