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This reduced-intensity conditioning (RIC) regimen was developed by the Washington University School of Medicine for children with severe thalassemia major undergoing unrelated donor hematopoietic cell transplantation (HCT). The regimen specifically combines alemtuzumab (a CD52-directed monoclonal antibody), fludarabine (a purine analog), and melphalan (an alkylating agent), often supplemented with thiotepa and hydroxyurea as part of the URTH trial protocol. The goal of this combination is to provide sufficient host immunosuppression to allow for stable engraftment of donor cells while minimizing the toxicities associated with traditional myeloablative conditioning. Alemtuzumab serves to deplete host T-cells to prevent graft rejection and graft-versus-host disease (GVHD), fludarabine provides lymphotoxicity and inhibits DNA synthesis, and melphalan acts as a cytoreductive agent to create space in the bone marrow.
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