cladribine + cytarabine + busulfan + azacitidine

This is a combination regimen consisting of four chemotherapeutic agents—cladribine, cytarabine, busulfan, and azacitidine. Each drug has a distinct mechanism of action targeting malignant hematologic cells:

• Cladribine is a purine nucleoside analog that interferes with DNA synthesis and repair, leading to apoptosis in both proliferating and non-proliferating cells.
• Cytarabine is a pyrimidine nucleoside analog that inhibits DNA polymerase during the S-phase of the cell cycle, resulting in impaired DNA synthesis and cell death.
• Busulfan is an alkylating agent that crosslinks DNA strands, preventing replication and transcription.
• Azacitidine is a hypomethylating agent that incorporates into RNA and DNA; it inhibits DNA methyltransferase, leading to hypomethylation of DNA and reactivation of tumor suppressor genes.

This multi-agent regimen may be used as part of conditioning therapy prior to hematopoietic stem cell transplantation or for the treatment of acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), particularly in high-risk or relapsed/refractory cases. The combination aims to maximize antileukemic efficacy by leveraging synergistic mechanisms from each component.