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The combination of cyclophosphamide, abatacept, and tacrolimus—sometimes referred to as the CAST regimen—is an investigational immunosuppressive protocol primarily studied for the prevention of graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (HSCT), especially in haploidentical or mismatched donor settings. Cyclophosphamide is a cytotoxic alkylating agent that induces apoptosis in activated T cells post-transplant. Abatacept is a fusion protein (CTLA4-Ig) that blocks T-cell activation by inhibiting CD28-mediated costimulation through binding to CD80/CD86 on antigen-presenting cells. Tacrolimus is a calcineurin inhibitor that suppresses T-cell activation by inhibiting interleukin-2 transcription. Together, these agents act synergistically to reduce the incidence and severity of acute GVHD while maintaining engraftment and minimizing relapse risk[2][6][7]. The regimen has shown promising safety and efficacy results in phase 1b/2 clinical trials for GVHD prophylaxis after peripheral blood haploidentical HSCT[2].
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