Targeting EBV-infected T cells with alemtuzumab: a novel approach to systemic chronic active EBV disease

Abstract

Alemtuzumab, a humanized monoclonal antibody against CD52, is approved for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to its strong immunosuppressive effects. We report the case of a 26-year-old woman with systemic chronic active Epstein-Barr virus disease (sCAEBV) who underwent allo-HSCT from an HLA-matched sibling donor with alemtuzumab-based GVHD prophylaxis. Her EBV-infected cells were CD4-positive T cells. Flow cytometry revealed an expansion of CD52-expressing CD4-positive T cells in peripheral blood (PB) with elevated EBV-DNA load. After treatment with alemtuzumab (0.16 mg/kg on Days - 10 and - 9), the CD4-positive cell fraction in PB declined rapidly, while EBV-DNA simultaneously decreased to an undetectable level. The conditioning regimen consisted of fludarabine (25 mg/m², Days - 7 to - 3), melphalan (40 mg/m², Days - 3 to - 2), and total body irradiation (TBI, 4 Gy, Day - 1). The serum concentration of alemtuzumab at transplantation was 0.36 μg/mL. Cyclosporine was given from Day - 1, and short-term methotrexate was given on Days 1, 3, and 6. The transplantation was successful, with no GVHD or severe infections. Earlier administration of alemtuzumab may not only reduce prolonged post-transplant immunosuppression but also speed up elimination of EBV-infected cells before transplantation for sCAEBV.

Keywords: Alemtuzumab; CD52; Hematopoietic stem cell transplantation; sCAEBV.