A Multicenter Analysis of the First Experience With Fk506 for Induction and Rescue Therapy After Pancreas Transplantation1

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% > or = 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 ...

Reversibility of tacrolimus-induced posttransplant diabetes: an illustrative case and review of the literature

“…Certainly, the potential for PTDM has not prevented the successful use of tacrolimus in kidney/pancreas transplantation, where a number of reports have described its efficacy. 18,19 When PTDM does occur under tacrolimus-based therapy, it is important not to reduce the dosage too quickly because acute rejection can occur. A gradual reduction in both tacrolimus and steroids will allow continued good graft function, and can lead to a normalization of blood sugars with the eventual discontinuation of insulin.…”

An Evidence‐Based Analysis of Simultaneous Pancreas‐Kidney and Pancreas Transplantation Alone

“…Excluded were 29 studies with abstract characters only, 20 reviews and five center reports without comparison with different protocols. Of the selected 10 papers, six were ranked level 1b (14,(28)(29)(30)(31)(32) and four level 2b (23,(33)(34)(35).…”

Long-Term Results of Pancreas Transplantation Under Tacrolimus Immunosuppression1

“…Additional data suggest that TAC may also yield longer half-lives for kidney transplants than standard CsA-based regimens (11). These observations have encouraged several centers, (8,12,13) including our own (14), to evaluate the safety and efficacy of TAC as primary therapy for pancreas transplantation. Thus far, reports with relatively short-term (one year or less) follow-up have confirmed the utility of TAC, and in some cases, suggested it is superior to CsA for SPK (8,12,14).…”

“…Its use is associated with a lower incidence of acute rejection in primary kidney transplantation compared with CsA in both U.S. and European multicenter trials (4, 5). TAC also has the ability to rescue kidney, liver, and pancreas grafts from rejection refractory to standard immunosuppressive protocols (6)(7)(8) and has the added advantage of permitting concomitant steroid tapering in both adult (9) and pediatric (10) renal transplantation, with up to 60% of patients eventually weaned from prednisone. Additional data suggest that TAC may also yield longer half-lives for kidney transplants than standard CsA-based regimens (11).…”