Alemtuzumab for the prevention and treatment of graft-versus-host disease

Abstract

Alemtuzumab is a humanized monoclonal antibody against the CD52 antigen, which is expressed on the surface of various hematopoietic cells such as B and T lymphocytes, and has been widely used for preventing acute graft-versus-host disease (GVHD) in allogeneic stem cell transplantation (SCT). Administration of 100 mg alemtuzumab before transplantation has resulted in a low incidence of acute GVHD in HLA-matched and mismatched transplantation from either related or unrelated donors. However, because alemtuzumab could remain in the blood at the lympholytic level 1-2 months after transplantation, immune reconstitution was substantially delayed, leading to a high incidence of viral infection and relapse. A dose reduction of alemtuzumab was attempted in a reduced-intensity conditioning setting to facilitate immune reconstitution, and this resulted in earlier immune reconstitution, but the clinical benefits were unclear. The dose of alemtuzumab and the timing of its administration should be optimized to maximize the benefit of acute GVHD suppression and minimize the risk of infection and relapse. Another strategy to facilitate immune reconstitution and augment anti-tumor effects is donor cell infusion of T and NK cells. Although there is accumulating evidence regarding the use of alemtuzumab for acute GVHD prevention, information on the salvage treatment for steroid-refractory acute and chronic GVHD is still limited.