Central nervous system failure in patients with chronic myelogenous leukemia lymphoid blast crisis and Philadelphia chromosome positive acute lymphoblastic leukemia treated with imatinib (STI-571)

Leuk Lymphoma. 2004 Apr;45(4):695-8. doi: 10.1080/10428190310001625728.


Isolated central nervous system (CNS) relapse occurred in 5 out of 24 patients (20.8%) with chronic myeloid leukemia (CML) lymphoid blast crisis (2), Philadelphia (Ph) chromosome positive acute lymphoblastic leukemia (ALL) (2) or CML with biphenotypic markers (1) treated on imatinib mesylate (IM) protocols at our institution. CNS relapse occurred despite peripheral blood (5) and bone marrow (3) complete responses. Median time to CNS relapse was day 32 (range 23 to 100). This observation raised the possibility that IM may not penetrate into the CNS. Simultaneous plasma and cerebral spinal fluid (CSF) IM levels were determined in four subsequent patients by liquid chromatography and mass spectrophotometric assay. Levels of IM were found to be approximately two logs lower in CSF than in plasma (0.044 microg/ml (0.088 +/- 0.029 micrro) vs 3.27 microg/ml (6.54 +/- 0.93 microM)). CSF levels were substantially below the concentration required for inhibition of BCR-ABL and killing of cell lines in vitro. These results suggest that IM may not penetrate the intact blood/brain barrier and its implications are discussed.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Benzamides
  • Blast Crisis / drug therapy
  • Blast Crisis / pathology*
  • Blood-Brain Barrier
  • Central Nervous System Neoplasms / etiology*
  • Female
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Piperazines / blood
  • Piperazines / cerebrospinal fluid
  • Piperazines / pharmacokinetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Pyrimidines / blood
  • Pyrimidines / cerebrospinal fluid
  • Pyrimidines / pharmacokinetics*
  • Recurrence
  • Remission Induction / methods
  • Tissue Distribution
  • Treatment Outcome


  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate