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Methotrexate + cyclosporin is a combination therapy used primarily for the prophylaxis of graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation. This regimen combines two distinct immunosuppressive mechanisms: methotrexate, a folate antimetabolite, and cyclosporin, a calcineurin inhibitor. Methotrexate acts by inhibiting dihydrofolate reductase, which disrupts DNA synthesis and cell proliferation, particularly in activated T-cells. Cyclosporin binds to cyclophilin to form a complex that inhibits calcineurin, thereby blocking the translocation of nuclear factor of activated T-cells (NFAT) and reducing the production of interleukin-2 (IL-2). Together, these agents provide synergistic suppression of donor T-cell activation and proliferation, reducing the risk of donor cells attacking host tissues. In clinical trials conducted by the Hospital Authority, Hong Kong, this combination has served as a standard-of-care control arm for evaluating the efficacy of adding further agents like mycophenolate mofetil to the prophylactic regimen.
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