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)

Jose F. Leis, Daniel E. Stepan, Peter T. Curtin, John M. Ford, Bin Peng, Susan Schubach, Brian Druker, Richard Maziarz

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

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 μg/ml (0.088 ± 0.029 μM) vs 3.27 μg/ml (6.54 ± 0.93 μM)). 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.

Original languageEnglish (US)
Pages (from-to)695-698
Number of pages4
JournalLeukemia and Lymphoma
Volume45
Issue number4
DOIs
StatePublished - Apr 2004

Fingerprint

Blast Crisis
Philadelphia Chromosome
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Central Nervous System
Recurrence
Blood-Brain Barrier
Liquid Chromatography
Bone Marrow
Imatinib Mesylate
Cell Line

Keywords

  • ALL
  • CML blast crisis
  • CNS leukemia
  • Imatinib

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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). / Leis, Jose F.; Stepan, Daniel E.; Curtin, Peter T.; Ford, John M.; Peng, Bin; Schubach, Susan; Druker, Brian; Maziarz, Richard.

In: Leukemia and Lymphoma, Vol. 45, No. 4, 04.2004, p. 695-698.

Research output: Contribution to journalArticle

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