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Cyclosporine + alemtuzumab is a combination therapy primarily investigated for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), particularly with reduced-intensity conditioning (RIC). Cyclosporine is a calcineurin inhibitor that suppresses T-cell activation by binding to cyclophilin and inhibiting the dephosphorylation of the nuclear factor of activated T-cells (NFAT), thereby reducing interleukin-2 production. Alemtuzumab (formerly CAMPATH-1H) is a humanized monoclonal antibody targeting CD52, a glycoprotein expressed on mature lymphocytes, monocytes, and macrophages. Its binding leads to profound and prolonged lymphopenia through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). This combination is used to mitigate the risk of acute and chronic GVHD in patients with B-cell neoplasms, such as chronic lymphocytic leukemia (CLL) and low-grade lymphomas, while attempting to preserve the graft-versus-tumor effect.
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