Intracellular cytarabine triphosphate in circulating blasts post-treatment predicts remission status in patients with acute myeloid leukemia.

Cytarabine remains the backbone of therapy in acute myeloid leukemia (AML). The ability to assess intracellular cytarabine triphosphate (ara-CTP) levels in patients receiving cytarabine represents a major goal in the prediction of treatment response. This study, conducted within a clinical setting, aimed to assess ara-CTP levels in circulating peripheral blasts from non-M3 AML patients receiving cytarabine at one of three dosing levels, using a novel biosensor assay.

CPX-351 exhibits hENT-independent uptake and can be potentiated by fludarabine in leukaemic cells lines and primary refractory AML.

CPX-351, a liposomal formulation co-encapsulating cytarabine and daunorubicin (DNR) in a synergistic 5:1 M ratio, has shown favourable response in newly diagnosed elderly high-risk AML. This study assessed intracellular ara-CTP levels following in vitro exposure of human immortalised leukaemic cell lines and primary AML blasts to CPX-351, and investigated fludarabine potentiation of intracellular ara-CTP formation from CPX-351. Comparison of intracellular handling of CPX-351 to cytarabine in HL-60 cells indicated slower conversion to ara-CTP for CPX-351, but equivalent cytotoxicity to cytarabine and combined DNR/cytarabine (DA) at 48 h, mostly likely reflecting the need for intracellular liposome processing to release encapsulated drugs.