Intestinal Transplantation for End Stage Crohnʼs Disease: Therapeutic Efficacy and Disease Recurrence

Abstract

Intestinal transplantation has recently evolved and more frequently utilized to rescue patients with irreversible intestinal failure who no longer can be maintained on TPN therapy. End stage Crohn's disease has been the second leading indication for transplantation in the adult population. This is the first study to address the procedure's therapeutic efficacy and the impact of disease recurrence on long-term outcome. Between May 2, 1990 and June 30, 2012, a total of 309 consecutive adult patients received 342 intestinal and multivisceral transplantations. Of these, 57 (18%) suffered recalcitrant Crohn's disease with irreversible intestinal failure for a mean duration of 5+5 years. All patients failed TPN therapy with multiple line infections (94%), limited venous access (83%), and significant liver damage (80%). The male to female ratio was 1:1.7 with a mean age of 43 + 10 years. All patients underwent multiple abdominal surgeries with proctocolectomy in 36 (63%). Simultaneous hepatic replacement was required in 12 (21%) patients due to end stage liver failure with a mean serum bilirubin of 9 + 11 mg/dL. The remaining 45 (79%) patients received liver-free visceral allografts with intestine alone in 43 and modified multivisceral graft including the stomach, duodenum, pancreas, and intestine in 2. Positive lymphocytotoxic crossmatch was documented in 14 (25%) recipients. All donors were cadaveric, ABO identical with random HLA crossmatch. Rejection prophylaxis was tacrolimus based in all patients with utilization of induction (cyclophosphamide/daclizumab) therapy in 8 (14%) and recipient pretreatment with rATG/alemtuzumab in 37 (65%) recipients. With a mean follow-up of 54 + 48 months, 33 (58%) of the Crohn's disease patients are currently alive with a retransplantation rate of 7%. Acute and chronic rejection was the leading cause of graft loss with an overall incidence of 56%. The actuarial patient survival rate was 90% at 1 year, 74% at 3 years, 56% at 5 years, and 43% at 10 years with respective graft survival of 86%, 65%, 53%, and 42%. Inclusion of the donor liver was associated with better long-term survival outcome with a 10-year survival rate of 57% for both patient and graft. Recipient pretreatment significantly improved patient survival with 1, 3, 5, and 10 year survival rates of 92%, 79%, 61% and 61%, respectively. All survivors achieved full nutritional autonomy enjoying unrestricted oral diet. Disease recurrence was histologically documented in 4 (7%) allografts at 3, 15, 18, and 19 months from the time of transplantation with no impact on graft function. With similar distribution of type of transplanted organs and immunosuppression, there was no significant (P = 0.6) difference in survival between the Crohn's and non-Crohn's patients. However, the cumulative risk of graft loss due to acute and chronic rejection was modestly higher in the Crohn's disease compared to the non-Crohn's disease patients. Intestinal and multivisceral transplantation is a life-saving and an effective therapy for patients with end stage Crohn's disease. Disease recurrence is very low and at best histologic with no significant impact on survival outcome and graft functions.