Pancreas transplantation without antibody therapy

After whole organ pancreas transplantation with duodenojejunostomy to drain the exocrine secretions was reintroduced in 1984,1 a few centers adopted this technique to replace transplantation of the body and tail of the pancreas, which had been the procedure of choice in the 1970s and early 1980s. Although in the early clinical trials using cyclosporine in whole organ pancreas transplantation, the incidence of thrombosis appeared to be less than with transplantation of the tail or “pancreatic segment,” it was by no means insignificant, and it was considered that cyclosporine, given its vasoconstrictive properties, might be a contributing factor.2 However, there were other reasons why the pancreas was more prone to thrombosis than either the kidney or the liver, in both of which there is a much higher blood flow by comparison with the pancreas. These factors include twisting or compression of the portal vein, ischemic injury, pancreatitis, and reperfusion injury. In addition, acute rejection played a role in early pancreas allograft loss. Therefore, it was believed that if a lower dose of cyclosporine (or no cyclosporine at all) was used in combination with an anti-T cell antibody administered during the first 10 days following transplantation, the incidence of acute rejection and thrombosis would be reduced. Most pancreas transplant centers in the United States and Europe adopted this immunosuppression regimen with delayed introduction of cyclosporine, the so-called “quadruple sequential immunosuppressive therapy,” introduced by Sollinger.3 In the late 1980s and 1990s, both patient and graft survival improved with this regimen, probably more as a result of technical refinements and a more restrictive policy of donor and recipient selection, than improvement in immunosuppression. In spite of these better results, surgically-related morbidity remained high,4 but this phenomenon was not related to the choice of immunosuppressive regimen. By mid-1995, experience had been gained in a few centers using tacrolimus-based immunosuppression in pancreas transplantation, and a multicenter analysis was presented in a preliminary fashion in 1996 by Gruessner,5 and again, with more complete data and greater patient accrual in 1997 at the annual meeting of the American Society of Transplant Surgeons (ASTS).6 All of the contributing centers but one (Pittsburgh) used tacrolimus in combination with antibody induction. Results of the retrospective multicenter analysis. presented by Gruessner, showed a 1 year patient and graft survival of 97% and 85%, respectively.6 Although the Pittsburgh group, which did not use anti T-cell induction therapy, contributed more patients than each of the other centers, except the University of Minnesota, in the multicenter retrospective analysis, the majority of the patients in the study had received antibody induction. Graft success rates were better with tacrolimus-based immunosuppression than with other drug regimens. In addition, graft survival improved substantially with tacrolimus in patients receiving a pancreas without a kidney, ie, pancreas after kidney transplantation (PAK) and pancreas transplant alone (PTA).6,7 However, these “solitary” graft recipients also received anti T-cell induction therapy in addition to tacrolimus. Although the data clearly showed that tacrolimus was superior to cyclosporine, it was difficult to conclude in a definitive fashion that the addition of an anti-T-cell preparation in combination with tacrolimus was necessary.