Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid

Nobuyuki Takayama, Norihide Sato, Stephen G. O'Brien, Yasuo Ikeda, Shinichiro Okamoto

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

A 32-year-old woman with relapsed Philadelphia chromosome-positive acute lymphoblastic leukaemia was treated with imatinib mesylate (formerly STI571), a selective inhibitor of BCR/ABL tyrosine kinase. Although the initial marrow response was good and stably maintained, she subsequently relapsed with extensive infiltration of leukaemic cells into the central nervous system (CNS). After controlling her CNS disease with additional intrathecal chemotherapy, we measured the concentration of imatinib in cerebrospinal fluid (CSF) and blood simultaneously. The concentration of imatinib in CSF was about 92-fold lower than that in blood. These results suggest that imatinib poorly penetrates the blood-brain barrier and has limited activity against CNS leukaemia.

Original languageEnglish
Pages (from-to)106-108
Number of pages3
JournalBritish Journal of Haematology
Volume119
Issue number1
DOIs
Publication statusPublished - 2002

Fingerprint

Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cerebrospinal Fluid
Central Nervous System
Central Nervous System Diseases
Blood-Brain Barrier
Protein-Tyrosine Kinases
Leukemia
Bone Marrow
Imatinib Mesylate
Drug Therapy

Keywords

  • Acute lymphoblastic leukaemia
  • Blood-brain barrier
  • Central nervous system
  • Imatinib mesylate
  • Philadelphia chromosome

ASJC Scopus subject areas

  • Hematology

Cite this

@article{46e3333ba08d40f69fdd88d39a44870c,
title = "Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid",
abstract = "A 32-year-old woman with relapsed Philadelphia chromosome-positive acute lymphoblastic leukaemia was treated with imatinib mesylate (formerly STI571), a selective inhibitor of BCR/ABL tyrosine kinase. Although the initial marrow response was good and stably maintained, she subsequently relapsed with extensive infiltration of leukaemic cells into the central nervous system (CNS). After controlling her CNS disease with additional intrathecal chemotherapy, we measured the concentration of imatinib in cerebrospinal fluid (CSF) and blood simultaneously. The concentration of imatinib in CSF was about 92-fold lower than that in blood. These results suggest that imatinib poorly penetrates the blood-brain barrier and has limited activity against CNS leukaemia.",
keywords = "Acute lymphoblastic leukaemia, Blood-brain barrier, Central nervous system, Imatinib mesylate, Philadelphia chromosome",
author = "Nobuyuki Takayama and Norihide Sato and O'Brien, {Stephen G.} and Yasuo Ikeda and Shinichiro Okamoto",
year = "2002",
doi = "10.1046/j.1365-2141.2002.03881.x",
language = "English",
volume = "119",
pages = "106--108",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid

AU - Takayama, Nobuyuki

AU - Sato, Norihide

AU - O'Brien, Stephen G.

AU - Ikeda, Yasuo

AU - Okamoto, Shinichiro

PY - 2002

Y1 - 2002

N2 - A 32-year-old woman with relapsed Philadelphia chromosome-positive acute lymphoblastic leukaemia was treated with imatinib mesylate (formerly STI571), a selective inhibitor of BCR/ABL tyrosine kinase. Although the initial marrow response was good and stably maintained, she subsequently relapsed with extensive infiltration of leukaemic cells into the central nervous system (CNS). After controlling her CNS disease with additional intrathecal chemotherapy, we measured the concentration of imatinib in cerebrospinal fluid (CSF) and blood simultaneously. The concentration of imatinib in CSF was about 92-fold lower than that in blood. These results suggest that imatinib poorly penetrates the blood-brain barrier and has limited activity against CNS leukaemia.

AB - A 32-year-old woman with relapsed Philadelphia chromosome-positive acute lymphoblastic leukaemia was treated with imatinib mesylate (formerly STI571), a selective inhibitor of BCR/ABL tyrosine kinase. Although the initial marrow response was good and stably maintained, she subsequently relapsed with extensive infiltration of leukaemic cells into the central nervous system (CNS). After controlling her CNS disease with additional intrathecal chemotherapy, we measured the concentration of imatinib in cerebrospinal fluid (CSF) and blood simultaneously. The concentration of imatinib in CSF was about 92-fold lower than that in blood. These results suggest that imatinib poorly penetrates the blood-brain barrier and has limited activity against CNS leukaemia.

KW - Acute lymphoblastic leukaemia

KW - Blood-brain barrier

KW - Central nervous system

KW - Imatinib mesylate

KW - Philadelphia chromosome

UR - http://www.scopus.com/inward/record.url?scp=0036399992&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036399992&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2141.2002.03881.x

DO - 10.1046/j.1365-2141.2002.03881.x

M3 - Article

VL - 119

SP - 106

EP - 108

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 1

ER -