Fludarabine is a synthetic purine analog antimetabolite used mainly in the treatment of chronic lymphocytic leukemia (CLL) and some low-grade non-Hodgkin lymphomas. It acts by inhibiting DNA synthesis, thereby preventing the proliferation of malignant lymphocytes and inducing cell death. Clinically, it is administered as fludarabine phosphate, which is converted inside the body to its active metabolite that interferes with enzymes essential for DNA replication. Historically, fludarabine was developed in the late 1970s as a modified form of vidarabine to improve stability and anticancer activity. Its therapeutic value became evident during the 1980s, when clinical trials showed superior efficacy compared to conventional alkylating agents in CLL. In 1991, fludarabine received FDA approval for use in previously treated CLL patients, marking a significant advancement in leukemia therapy, and it later became an important component of combination chemotherapy regimens and stem cell transplant conditioning protocols.
