Low Dasatinib Penetration of the Blood-Brain Barrier in Children With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Evidence From LC-MS/MS Analysis.

We measured dasatinib concentrations in paired plasma and cerebrospinal fluid (CSF) samples from children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Blood samples were collected from children at 0 h (pre-dasatinib) and 2 h post-dasatinib, along with CSF. After validating a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for dasatinib in both matrices, we quantified drug concentrations in plasma and CSF and expressed blood-brain barrier penetration as the plasma-to-CSF concentration ratio. Twenty children with Ph+ ALL, who received oral dasatinib (60-80 mg/m2·day), were included in this study. The median age was 10.8 (5-16) years, with 13 males (65%) and 7 females (35%). In plasma, the mean dasatinib concentrations were 1.3 ± 0.7 ng/mL at 0 h and 101.6 ± 42.1 ng/mL at 2 h. In CSF, the mean dasatinib concentration was 0.5 ± 0.2 ng/mL at 2 h. The median paired plasma/CSF concentration ratio was 225:1 (98:1-406:1). In conclusion, despite therapeutic systemic levels, dasatinib penetrates poorly into CSF in children with Ph+ALL.