Safety and Efficacy of Alemtuzumab Induction in Highly Sensitized Pediatric Renal Transplant Recipients

Abstract

Background: Studies show that alemtuzumab, a potent lymphocyte-depleting agent, is well tolerated in pediatric renal transplantation. We report on the use of alemtuzumab induction in highly HLA sensitized (HS) pediatric kidney transplant patients.

Methods: Fifty pediatric renal transplants were performed from 1/2009-12/2014. 15 HS patients received IVIG (2 g/kg ×2 doses)/rituximab (375 mg/m ×1) for desensitization with alemtuzumab induction (15-30 mg, 1 dose, subcutaneous), whereas 35 nonsensitized patients received anti-IL-2R. Graft survival and infections were compared between 2 groups.

Results: All HS patients had received a prior transplant and were older with lower risk for viral infections due to serostatus. Patient survival was 100%, and graft outcomes were similar with mean 1-year creatinine of 1.03 ± 0.45 versus 0.99 ± 0.6 (P = 0.48). Although a higher incidence of acute cellular rejection was seen in HS patients receiving alemtuzumab (P = 0.001), there was a nonsignificant difference in antibody-mediated rejection. White blood cell and absolute lymphocyte count were significantly lower in alemtuzumab group at 30 days (P < 0.0001) and at 1 year (P = 0.026 and P = 0.001), respectively. There was no significant difference in bacterial, viral, or fungal infections after transplant.

Conclusions: Alemtuzumab induction with desensitization led to nearly equivalent graft survival and functional outcomes in HS pediatric patients as nonsensitized patients receiving anti-IL-2R induction. With this small sample size, we observed significant reduction of white blood cell and absolute lymphocyte count up to 1 year posttransplant. The risk of infection was comparable between the 2 groups; however, patients who received alemtuzumab were older and at lower risk of viral infection due to serostatus.

FIGURE 1.

Pediatric desensitization protocol and alemtuzumab use in highly sensitized pediatric renal transplant recipients.

FIGURE 2.

Graft survival. Kaplan-Meier graft survival curve demonstrates that no significant difference in graft survival between pediatric patients who received alemtuzumab induction versus anti–IL-2 R induction.

FIGURE 3.

Kaplan-Meier curves demonstrate freedom from rejection between patients who received alemtuzumab induction versus anti–IL-2R induction. There were significantly more rejection events, total and cell-mediated rejection, in the alemtuzumab group (A, B); however, there was no difference in AMR between the 2 groups (C).

FIGURE 4.

Lymphocyte depletion. Box plots demonstrate a significant difference in both WBC (A, B, C) and ALC (D, E, F) at 30, 180, and 365 days for patients who received alemtuzumab induction.