TACROLIMUS IN PANCREAS TRANSPLANTATION - A MULTICENTER ANALYSIS

This follow-up multicenter analysis is based on 362 pancreas allograft recipients at 14 institutions who were given tacrolimus between 1 May 1994 and 15 November 1995, Three groups were studied: (1)recipients g iven tacrolimus initially for induction and maintenance therapy (n=250 ; 215 without, 35 with, a concurrent bone marrow transplant), (2) reci pients who converted to tacrolimus for rescue or rejection therapy (n= 89), and (3) recipients who converted to tacrolimus for other reasons (n=23). Of 215 recipients without a bone marrow transplant in the indu ction group, 166 (77%) underwent a simultaneous pancreas-kidney transp lant (SPK), 29 (14%) a pancreas transplant alone (PTA), and 20 (9%) a pancreas after previous kidney transplant (PAK). Initial antibody ther apy was given to 185 (86%) recipients. All 215 received tacrolimus and prednisone; 202 (94%) also received azathioprine (AZA) and 11 (5%) my cophenolate mofetil (MMF). The most common side effects of tacrolimus were neurotoxicity in 21%, nephrotoxicity in 21%, gastrointestinal (GI ) toxicity in 13%, and diabetogenicity in 13% of these recipients. No recipient in this group developed new-onset insulin-dependent diabetes mellitus.Of 89 recipients in the rescue group, 71 (79%) had an SPK, 1 1 (13%) a PTA, and 7 (8%) a PAK. Before conversion, all had been on cy closporine (CsA)-based immunosuppression; 74% of them had 2 or more re jection episodes previously. The most common side effects were nephrot oxicity in 27%, neurotoxicity in 26%, GI toxicity in 18%, and diabetog enicity in 8% of these recipients, No recipient in this group develope d new-onset insulin-dependent diabetes mellitus. In the induction grou p, patient survival at 1 yr was 98% for SPK, 79% for PTA, and 100% for PAK recipients, According to a matched-pair analysis, pancreas graft survival for SPK recipients at 1 yr was 88% with tacrolimus vs. 73% wi th CsA (p=0.002); for PTA recipients, 68% vs. 70% (p>0.35); and for PA K recipients, 85% vs, 65% (p=0.13), Graft loss from rejection was not different with tacrolimus vs. CsA in all 3 pancreas recipient categori es, At 1 yr, 17% of recipients had converted from tacrolimus to CsA fo r diabetogenicity, nephrotoxicity, or rejection; 23% had converted fro m AZA to MMF. The incidence of posttransplant lymphoma was <2%. In the rescue group, patient survival rates at 1 yr were 96% for SPK, 100% f or PTA, and 86% for PAK recipients (p<0.08). Pancreas graft survival a t 1 yr was 89% for SPK, 58% for PTA, and 69% for PAK recipients (p=0.0 04). Graft loss from rejection was significantly lower for SPK vs. PTA or PAK recipients. At 1 yr, 20% of recipients had reconverted from ta crolimus to CsA for rejection, neurotoxicity, or nephrotoxicity; 19% h ad converted from AZA to MMF. There were no post-transplant lymphomas in the rescue group. This follow-up multicenter analysis shows that ta crolimus after pancreas transplantation is associated with high graft survival rates when used for induction and with high graft salvage rat es when used for rescue therapy, The rate of graft loss from rejection is low in all 3 pancreas recipient categories. The overall incidence of new-onset insulin-dependent diabetes mellitus is <1%, as is the inc idence of post-transplant lymphoma. Converting from tacrolimus to CsA and, in patients on tacrolimus, from AZA to MMF, is safe; interchangea ble use of drugs appears to be of immunologic benefit. To determine th e best immunosuppressive regimen after pancreas transplantation, a pro spective randomized study comparing tacrolimus and MMF vs. Neoral plus MMF is mandatory.