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Cyclophosphamide + fludarabine + melphalan (often abbreviated as the FCM or Flu/Cy/Mel regimen) is a combination chemotherapy regimen primarily utilized as a reduced-intensity conditioning (RIC) or myeloablative preparative regimen prior to allogeneic hematopoietic stem cell transplantation (alloHCT). The regimen combines two alkylating agents, cyclophosphamide and melphalan, with the purine nucleoside analog fludarabine. Cyclophosphamide and melphalan act by covalently binding to DNA, inducing inter-strand and intra-strand cross-links that disrupt DNA replication and transcription, leading to cell death. Fludarabine is intracellularly phosphorylated to its active triphosphate form, which inhibits DNA polymerase alpha, ribonucleotide reductase, and DNA primase, thereby halting DNA synthesis and repair. Together, this combination provides potent myelosuppression and lymphodepletion, facilitating donor engraftment and reducing the risk of graft rejection and relapse in patients with hematologic malignancies (such as acute myeloid leukemia and myelodysplastic syndrome) or severe aplastic anemia.
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