fludarabine + cladribine

fludarabine + cladribine is an experimental combination of two purine nucleoside analog antimetabolites used primarily in hematologic malignancies and conditioning regimens for hematopoietic stem cell transplantation. Both agents are phosphorylated intracellularly by deoxycytidine kinase to their active triphosphate forms, which are incorporated into DNA and inhibit DNA synthesis and repair, leading to DNA strand breaks and apoptosis, with particular cytotoxicity toward proliferating and resting lymphocytes and leukemic blasts. The combination is explored mainly in acute leukemias and transplant conditioning as an intensified purine analogue backbone, sometimes together with agents such as busulfan, thiotepa, or venetoclax, to deepen cytoreduction and potentially improve remission quality and transplant outcomes compared with fludarabine-based regimens alone.