Association of More Intensive Induction With Less Acute Rejection Following Intestinal Transplantation: Results of 445 Consecutive Cases From a Single Center

Abstract

BACKGROUND: In intestinal transplantation, acute cellular rejection (ACR) remains a significant challenge to achieving long-term graft survival. It is still not clear which are the most important prognostic factors. METHODS: We performed a Cox multivariable analysis of the hazard rates of developing any ACR, severe ACR, and cause-specific graft loss during the first 60 months posttransplant among 445 consecutive intestinal transplant recipients at our institution since 1994. Of particular interest was to determine the prognostic influence of induction type: rabbit antithymocyte globulin (rATG; 2 mg/kg × 5)/rituximab (150 mg/m × 1; begun in 2013), alemtuzumab (2001-2011), and less intensive forms. RESULTS: First ACR and severe ACR occurred in 61.3% (273/445) and 22.2% (99/445) of cases. The following 3 multivariable predictors were associated with significantly lower hazard rates of developing ACR and severe ACR: transplant type modified multivisceral or full multivisceral (P = 0.0009 and P < 0.000001), rATG/rituximab induction (P < 0.000001 and P < 0.01), and alemtuzumab induction (P = 0.004 and P = 0.07). For both ACR and severe ACR, the protective effects of rATG/rituximab and alemtuzumab were highly significant (P ≤ 0.000005 for ACR; P ≤ 0.01 for severe ACR) but only during the first 24 days posttransplant (when the ACR hazard rate was at its peak). The prognostic effects of rATG/rituximab and alemtuzumab on ACR/severe ACR disappeared beyond 24 days posttransplant (ie, nonproportional hazards). While significant protective effects of both rATG/rituximab and alemtuzumab existed during the first 6 months posttransplant for the hazard rate of graft loss-due-to-rejection (P = 0.01 and P = 0.003), rATG/rituximab was additionally associated with a consistently lower hazard rate of graft loss-due-to-infection (P = 0.003). All significant effects remained after controlling for the propensity-to-be-transplanted since 2013. CONCLUSIONS: More intensive induction was associated with a significant lowering of ACR risk, particularly during the early posttransplant period.