Subcutaneous Alemtuzumab as Salvage Therapy for Acute Kidney Transplant Rejection Following Thymoglobulin Anaphylaxis: A Pediatric Case Report.

BACKGROUND: Acute kidney allograft rejection is a significant cause of graft dysfunction in pediatric transplant recipients. Standard of care for moderate to severe acute T-cell-mediated rejection among pediatric transplant recipients includes lymphocyte-depleting agents such as rabbit anti-thymocyte globulin (rATG). However, intolerance to or contraindications to rATG may limit its use and necessitate alternative immunosuppressive strategies. Alemtuzumab, a humanized monoclonal antibody targeting CD52, induces profound depletion of T- and B- lymphocytes and has been used in the transplantation setting. However, data remain limited for pediatric rejection, and the precise role for alemtuzumab is not well defined.

CASE PRESENTATION: We report a 12-year-old male with end-stage kidney disease secondary to congenital renal dysplasia who underwent deceased donor kidney transplantation and presented 9 years post-transplant with acute allograft dysfunction. Evaluation revealed a rise in serum creatinine, subtherapeutic tacrolimus levels, and increased donor-specific antibodies. Kidney biopsy demonstrated Banff grade IIA T-cell-mediated rejection with features of antibody-mediated rejection. Initial treatment included high-dose corticosteroids and intravenous immunoglobulin. rATG therapy was initiated but discontinued due to anaphylaxis. The patient subsequently received a 30-mg dose of subcutaneous alemtuzumab, which was well tolerated. B- and T-lymphocyte populations were suppressed on flow cytometry analysis. Kidney function significantly improved, repeat biopsy showed marked improvement in tubulointerstitial inflammation, and graft function remained stable at follow-up.

CONCLUSIONS: This case highlights the potential role of alemtuzumab as an alternative lymphocyte-depleting therapy for the treatment of acute rejection in pediatric kidney transplant recipients, particularly when rATG is contraindicated. Moreover, treatment with alemtuzumab may preclude the need for additional B-cell directed therapy in cases of mixed T-cell- and antibody-mediated rejection. Further studies are needed to better define its safety, efficacy, and optimal role in this population.