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

Transplantation. 2017 Apr;101(4):883-889. doi: 10.1097/TP.0000000000001416.

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.

MeSH terms

  • Adolescent
  • Age Factors
  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Biomarkers / blood
  • Child
  • Desensitization, Immunologic / adverse effects
  • Desensitization, Immunologic / methods*
  • Drug Therapy, Combination
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / mortality
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects*
  • HLA Antigens / immunology*
  • Histocompatibility*
  • Humans
  • Immunocompromised Host
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Isoantibodies / blood
  • Kaplan-Meier Estimate
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / mortality
  • Lymphocyte Count
  • Lymphocyte Depletion / adverse effects
  • Lymphocyte Depletion / methods*
  • Male
  • Opportunistic Infections / immunology
  • Opportunistic Infections / virology
  • Retrospective Studies
  • Risk Factors
  • Rituximab / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • HLA Antigens
  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents
  • Isoantibodies
  • Alemtuzumab
  • Rituximab