cyclophosphamide + sirolimus + mycophenolate mofetil

**Cyclophosphamide + sirolimus + mycophenolate mofetil** is a combination immunosuppressive regimen primarily used as graft-versus-host disease (GVHD) prophylaxis following reduced intensity conditioning and peripheral blood stem cell transplantation (PBSCT) for hematologic malignancies. **Cyclophosphamide**, a nitrogen mustard alkylating agent activated in the liver to 4-hydroxycyclophosphamide, cross-links DNA strands to inhibit rapidly proliferating cells, including T-cells, enabling selective allodepletion post-transplant. **Sirolimus** (rapamycin), an mTOR inhibitor, suppresses T-cell activation and proliferation by binding FKBP12 to inhibit mTORC1, promoting regulatory T-cells. **Mycophenolate mofetil (MMF)** inhibits inosine monophosphate dehydrogenase, selectively depleting lymphocytes by blocking guanosine nucleotide synthesis essential for DNA replication. This triplet reduces acute GVHD rates (grade III-IV) and primary graft failure while preserving graft-versus-tumor effects, evaluated in phase I/II trials for HLA-matched and haploidentical settings.[1][5][7]

Other names

GVHD prophylaxisPost-transplantation cyclophosphamide + sirolimus + mycophenolate mofetilGVHD prophylaxis-National Cancer Institute (NCI)-peripheral T-cell lymphoma