Alemtuzumab Induction in Pediatric Kidney Transplantation

Abstract

Introduction: Recipient parenchymal lymphatic cells are crucial for semidirect and indirect pathways of allorecognition and development of chronic rejection. We and others proposed that alemtuzumab, being infused several weeks pretransplant could eradicate peripheral lymphatic cells and promote donor-specific tolerance. Method: 107 children (54 boys, 53 girls; age 0,7 to 18 years) received living related kidney transplant in Russian Scientific Center of Surgery from September 2006 to January 2011. The major causes for recipients' ESRD were reflux nephropathy (29 %) and dysplasia (23%). Diseases that recur in the graft represented a small portion of our patients (5% primary FSGS). The average HLA mismatch was 2.5±1.0. Immunosupression (IS) protocol included two 30 mg doses of alemtuzumab: first given 12-29 days prior to transplantation and second on day of transplant. Maintenance IS was based on combination of low dose CNI and mycophenolate. Steroids were discontinued after achievement of target CNI level, usually by Day 5. IS was decreased in cases of BK viruria above 107 copies/ml, repeated BK or EBV viremia and recurrent CMV viremia. Patients were followed for 1192±470 days and protocol biopsies were taken 1 month, 1 and 3 year post transplant. Results: The Kaplan-Meier graft and patient survival was 95% and 97% for one year, 88% and 93% for three years, 84% and 90% for five years. Delayed graft function occurred in 7 patients. Biopsy proven acute rejection (BPAR) developed in 26% patients at one year and in 35% at two years, no rejections occurred behind 2 years. BANFF scores were borderline in 59%, 1a in 34%, 1b in 0.5%, 2a in 5% and 2b in 1% of all rejections. Among 93 patients with functioning grafts the decline of graft function by estimated GFR and degree of proteinuria between discharge and last control were not significant: 92±34 and 82±37 ml per min; 220±260 and 189±149 mg per day. Infections: All patients received prophylaxis with Valgancyclovir for 3 weeks after transplantation. CMV, EBV and BK viremia were monitored monthly during first post-transplant year, thereafter every 3 months. In case of detectable CMV-viremia preemptive therapy with Valgancyclovir was re-introduced. CMV and BKV viremia were noticed in 30% and 25% of all patients correspondingly during first 3 months and in less than 10 and 5% after first year. Prevalence of EBV viremia was reaching 20% at 2 years. We have not detected any cases of PTLD in our population; however 2 kids had lymphadenopathy associated with EBV-viremia that improved after discontinuation of CNI. At last follow up 53 patients was receiving combination of CNI+MMF, 15 MMF+PSI, 10 CNI+MMF+steroids, 6 mycophenolate alone, 3 CNI alone, 2 MMF+steroids, 2 CNI+steroids, 1 PSI+MMF+steroids and 1 CNI+Aza+steroids. Free of steroids remain 83% of patients. Conclusion: Alemtuzumab pretreatment prior to LRD kidney transplantation allows to reach satisfactory middle-term results and maintain steroid-free immunosuppressive protocol in the majority of pediatric patients.