fludarabine + cyclophosphamide + melphalan

Fludarabine + cyclophosphamide + melphalan is a combination chemotherapy regimen used as a conditioning therapy prior to hematopoietic cell transplantation (HCT), particularly in haploidentical settings with post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis. Fludarabine inhibits DNA synthesis by incorporating into DNA as a false nucleotide, cyclophosphamide acts as an alkylating agent forming DNA crosslinks, and melphalan, another alkylating agent, binds DNA to prevent replication. This myeloablative or reduced-intensity combination provides effective disease control in hematologic malignancies but carries risks of high non-relapse mortality, severe cytokine release syndrome, and toxicity, especially with peripheral blood grafts.