clofarabine + fludarabine + busulfan

Clofarabine + fludarabine + busulfan is a combination chemotherapy regimen used primarily as a conditioning treatment before allogeneic hematopoietic stem cell transplantation (HCT), especially in patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and acute lymphoblastic leukemia (ALL). This regimen combines two nucleoside analogs, clofarabine and fludarabine, with the DNA alkylating agent busulfan. The combination is designed to maximize antileukemic activity through synergistic cytotoxicity while potentially reducing individual drug toxicity by allowing lower doses of each component. Mechanistically, clofarabine and fludarabine inhibit DNA synthesis by incorporating into DNA and inhibiting ribonucleotide reductase, while busulfan induces cross-linking of DNA strands leading to cell death. The triple-drug regimen has shown enhanced cytoreductive effects compared to dual combinations or single agents, activating pathways such as ATM-mediated DNA damage response and chromatin remodeling[2][3][5][6]. It remains investigational for this specific three-drug use in most regions.

Other names

CloFluBu