*Purpose: T cell-depleting antibody therapy with rabbit anti-thymocyte globulin (rATG) is the treatment of choice for glucocorticoid-resistant, recurrent and/or severe acute kidney allograft rejection (AR). Although effective, the use of rATG is associated with serious infusion-related side effects. Alemtuzumab, a humanized rat monoclonal antibody against CD52, is incidentally used as off-label treatment for AR. Following satisfactory results in a pilot study, alemtuzumab has become the first line T-cell depleting agent in our center. Here, the long-term outcomes (patient- and allograft outcomes, and adverse events) were compared of patients treated with either alemtuzumab or rATG for AR.

*Methods: Between 2012 to 2017, we identified 113 patients, treated with alemtuzumab (30 mg, subcutaneously) for biopsy-proven glucocorticoid-resistant, recurrent or severe AR (Banff acute T cell-mediated rejection grade IIA or more). Long-term outcome was compared with the outcome of a retrospective cohort of 108 patients treated with rATG for AR between 2002 and 2012.

*Results: Patient survival between patients treated with alemtuzumab or rATG was similar (p=0.05, hazard ratio (HR) 2.08, 95%-confidence interval (CI) 0.99-4.34). Death-censored allograft survival after AR was comparable between both groups (p=0.87, HR 0.96, 95%-CI 0.62-1.50). A multivariate Cox regression analysis of alemtuzumab-treated patients showed 4 variables that influenced allograft survival negatively: no maintenance immunosuppressive therapy with glucocorticoids, actual panel reactive antibodies above 6%, estimated glomerular filtration rate (eGFR) drop of more than 50% between baseline eGFR and eGFR at time of AR, and remarkably, a lower HLA mismatch. Infusion-related adverse events occurred less often after alemtuzumab treatment: No patients developed cytokine release syndrome or serum sickness. Infection-free survival in the first year after alemtuzumab treatment was superior compared with the infection-free survival of rATG-treated patients (p=0.002, HR 0.54, 95%-CI 0.37-0.84). After alemtuzumab (median follow-up 2.63 years [interquartile range 1.3-3.6]), 7 solid tumors occurred.

*Conclusions: Patient- and allograft survival were comparable between patients treated for severe AR with either alemtuzumab and rATG. However, in the alemtuzumab-treated patients, fewer infusion-related side effects and less infections occurred. Alemtuzumab therapy is a good alternative therapy for glucocorticoid-resistant, recurrent and/or severe AR.

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