The clinical introduction of tacrolimus ushered in a new era in the field of intestinal and multivisceral transplantation. Soon after the initiation of the clinical trial with tacrolimus and steroid-based immunosuppression (type I), most centers experienced prohibitive risk of allograft rejections. During such an exciting era, different novel approaches were also introduced due to the introduction of new immunosuppressive agents with new insights into the mechanism of allograft acceptance and transplant tolerance.

With more emphasis on the difficulty of clinical care rather than survival, induction therapy with cyclophosphamide and daclizumab was introduced as part of multiple-drug immunosuppression including different cellular and molecular targets (type II) (Fig. 38.3). With better control of rejection, the overall survival has improved at major centers and according to the Intestinal Transplant Registry (ITR) [4, 28–30]. Unfortunately, updated results confirmed the long-term detrimental effect of chronic multiple-drug maintenance immunosuppression with erosion of the observed early survival benefits beyond the 10-year post-transplant landmark [4] (Fig. 38.4a).

With new insights into the mechanism of allograft acceptance and transplant tolerance, recipient preconditioning using thymoglobulin or alemtuzumab (Campath-1H) (Fig. 38.4b) with post-transplant minimal immunosuppression was introduced (type III) with the aim to improve allograft stability and reduce the need for long-term post-transplant immunosuppression at the University of Pittsburgh [31–33]. With perioperative partial depletion of the recipient lymphoid cells, amelioration of the initial donor-specific immune response is expected. Jointly application of minimal post-transplant immunosuppression has the potential to avoid the possible erosion of the alloengraftment mechanism of clonal exhaustion-deletion without high penalty of destructive immune response [32, 33]. The Pittsburgh intestinal and multivisceral recipients were the first to receive such a novel protocol with further improvement in overall outcome [4]. Reduction in the total incidence of intractable rejection and fatal infections partially contributed to better overall survival. Equally encouraging is the concomitant reduction in risk and fatality of PTLD despite the depletion of recipient lymphoid cells. With such a novel protocol, further improvement in outcome was achieved with more survival advantage utilizing alemtuzumab compared to rabbit antithymocyte globulin (thymoglobulin) (Fig. 38.5) [9]. A similar protocol has been reported by the Miami group utilizing alemtuzumab as an induction and not a pretreatment agent with multiple perioperative doses with no attempts to space out the tacrolimus maintenance dosage [34, 35].