cyclophosphamide + fludarabine + mycophenolate mofetil + sirolimus

This is a combination regimen consisting of four immunosuppressive and cytotoxic agents—cyclophosphamide, fludarabine, mycophenolate mofetil, and sirolimus. It is primarily used in the context of allogeneic hematopoietic stem cell transplantation (HSCT) as part of graft-versus-host disease (GVHD) prophylaxis or conditioning regimens. - Cyclophosphamide is an alkylating agent that crosslinks DNA, leading to cell death; it has both cytotoxic and immunosuppressive properties. - Fludarabine is a purine analog that inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase activity, resulting in immunosuppression and antitumor effects. - Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase (IMPDH), suppressing lymphocyte proliferation by blocking de novo guanosine nucleotide synthesis[5][7]. - Sirolimus inhibits the mammalian target of rapamycin (mTOR), thereby blocking T-cell activation and proliferation in response to interleukin-2[4]. This multi-agent regimen aims to reduce the risk of GVHD while maintaining effective engraftment after transplantation. The combination leverages complementary mechanisms for robust immunosuppression with reduced nephrotoxicity compared to calcineurin inhibitor-based regimens[1][2][3].