Alemtuzumab induction and prednisone-free maintenance immunotherapy in simultaneous pancreas-kidney transplantation comparison with rabbit antithymocyte globulin induction - long-term results.

This study compared the effects of using two T-cell depleting antibodies, alemtuzumab (anti-CD 52, Campath-1H) and rabbit antithymocyte globulin (Thymoglobulin), as induction immunosuppression for recipients of simultaneous pancreas-kidney transplantation given a prednisone-free maintenance regimen. We used a single-center, nonrandomised, retrospective, sequential study design to evaluate the efficacy and safety of alemtuzumab (n = 50) or antithymocyte globulin (n = 38) induction in combination with a prednisone-free, tacrolimus/sirolimus-based immunosuppression protocol. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent. Secondary endpoints included the quality of renal allograft function, incidence of infectious and malignant complications, and cost considerations. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and antithymocyte globulin. Rejection rates were also nearly equivalent at 1 and 2 years. Viral infectious complications were statistically significantly lower in the alemtuzumab group. The cost of alemtuzumab induction was lower than antithymocyte globulin. Alemtuzumab induction followed by steroid-free maintenance therapy with a tacrolimus/sirolimus-based immunosuppression regimen provided an effective, safe and cost-conscious approach to SPK transplantation.

Risk factors and impact of cytomegalovirus disease in simultaneous pancreas-kidney transplantation.

BACKGROUND: The relevance of cytomegalovirus (CMV) in simultaneous pancreas kidney (SPK) transplant recipients in the modern era of immunosuppression and antiviral therapeutics is largely unquantified. We sought to determine the risk factors of CMV disease and its impact on SPK transplant outcomes in recipients all receiving a consistent regime of maintenance immunosuppression and CMV prophylaxis. METHODS: This is a retrospective, single center study of 100 consecutive SPK transplant recipients. All received maintenance immunosuppression with mycophenolate mofetil, tacrolimus, and prednisone. CMV prophylaxis consisted of a short course of parenteral gancyclovir followed by oral gancyclovir. Recipients at high-risk (D+/R-) for CMV also received CMV hyperimmune globulin. Multivariate analysis of risk factors for CMV disease and risk factors for adverse outcomes in SPK transplantation were determined. The effect of duration of prophylaxis on timing and severity of CMV disease in high-risk (D+/R-) SPK transplant recipients was also evaluated. RESULTS: The actual 1-year rate of CMV disease was 17.0% (12.0% noninvasive, 5.0% tissue invasive); and according to donor and recipient CMV serological status was: D-/R+: 0%; D-/R-: 2.8%; D+/R+: 25.6%; and D+/R-: 40.6%. Multivariate analysis showed transplantation of organs from a donor with positive CMV serology to be predictive of CMV disease with a relative risk of 63.37 (P=0.0052). In the high-risk (D+/R-) subgroup, the duration of prophylactic therapy delayed onset of CMV disease, but had minimal effect on severity. Invasive CMV disease was an independent predictor of mortality but did not decrease kidney or pancreas allograft survival. CONCLUSIONS: Outcomes of SPK transplantation have improved in the current era of modern immunosuppression, yet CMV remains an important pathogen. The serological status of the organ donor and the duration of CMV prophylaxis are predictive of who and when CMV disease may occur. Nevertheless, new strategies that reduce risk and severity of CMV disease are still needed.

Pancreas transplantation at Northwestern University.

The collective advances made by many groups have significantly improved the results of pancreas transplantation. We have focused on the development of safe and effective immunotherapy, including a new protocol of rapid withdrawal of corticosteroids, the analysis of surgical technique of pancreas exocrine drainage on outcome and the role of SPK transplantation in patients with significant cardiovascular disease. We have found that multimodal immunotherapy including induction with tacrolimus-based maintenance combined with either MMF or sirolimus, with or without corticosteroids, resulted in excellent patient and graft survival rates with low rates of rejection. In this setting, enteric drainage was preferable to bladder drainage because of a lower rate of complications leading to hospital readmissions. Careful pretransplant screening for cardiovascular disease should be routinely performed for all SPK candidates. If successful coronary revascularization can be achieved, these patients can safely undergo SPK transplantation, with 5-year outcomes similar to those for recipients without coronary disease. Finally, we have observed that pancreas transplantation has an important ameliorating effect on hypertension that is independent of the method of pancreas exocrine drainage.