fludarabine + cytarabine + dexamethasone + asparaginase

The combination of fludarabine, cytarabine (Ara-C), dexamethasone, and asparaginase (often abbreviated as FLAD-asparaginase) is an intensive salvage chemotherapy regimen primarily used for the treatment of relapsed or refractory acute lymphoblastic leukemia (ALL). This multi-drug strategy utilizes biochemical synergism to overcome resistance in lymphoblasts. Fludarabine, a purine analog, acts as a prodrug that is phosphorylated to its active triphosphate form (F-ara-ATP), which inhibits ribonucleotide reductase and DNA polymerase, and importantly, enhances the intracellular accumulation of cytarabine's active metabolite (Ara-CTP). Cytarabine subsequently incorporates into DNA, causing chain termination and cell death. Dexamethasone, a potent glucocorticoid, induces apoptosis in lymphoid cells by activating the glucocorticoid receptor. Asparaginase provides a metabolic hit by hydrolyzing extracellular L-asparagine into L-aspartic acid and ammonia, depriving leukemic cells—which typically lack the enzyme asparagine synthetase—of an essential amino acid required for protein synthesis.

Other names

FLAD-asparaginaseFLAD-L-asparaginaseFLAD-L-AspFLAD regimenFLADA