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/m 2 ·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.