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Annals of Hematology
Published in: Annals of Hematology 6/2004

01-06-2004 | Case Report

CNS blast crisis of chronic myelogenous leukemia in a patient with a major cytogenetic response in bone marrow associated with low levels of imatinib mesylate and its N-desmethylated metabolite in cerebral spinal fluid

Authors: Martin Bornhauser, Andreas Jenke, Jens Freiberg-Richter, Jörgen Radke, Ulrich S. Schuler, Brigitte Mohr, Gerhard Ehninger, Eberhard Schleyer

Published in: Annals of Hematology | Issue 6/2004

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Abstract

Imatinib mesylate (STI571) is a very effective treatment option for Ph+ chronic myeloid leukemia (CML) in chronic phase. Secondary treatment failures have mostly been observed in patients with advanced stages of disease. We report the case of a patient who unexpectedly experienced blast crisis of the central nervous system although having achieved complete cytogenetic remission in the bone marrow. The levels of STI571 and its metabolite N-desmethyl STI were 40-fold lower in the cerebral spine fluid than in plasma. The risk of CNS disease has to be kept in mind when patients with CML in chronic phase who are at an increased risk for blastic transformation are treated with imatinib mesylate.
Literature
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Hochhaus A, Kreil S, Corbin A, La Rosee P, Lahaye T, Berger U, Cross NC, Linkesch W, Druker BJ, Hehlmann R, Passerini C, Corneo G, D’Incalci M (2001) Roots of clinical resistance to STI-571 cancer therapy. Science 293:2163
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Mahon FX, Belloc F, Lagarde V, Chollet C, Moreau-Gaudry F, Reiffers J, Goldman J M, Melo JV (2003) MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 101:2368–2373CrossRefPubMed
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Petzer AL, Gunsilius E, Hayes M, Stockhammer G, Duba HC, Schneller F, Grunewald K, Poewe W, Gastl G (2002) Low concentrations of STI571 in the cerebrospinal fluid: a case report. Br J Haematol 117:623–625CrossRefPubMed
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Takayama N, Sato N, O’Brien SG, Ikeda Y, Okamoto S (2002) 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. Br J Haematol 119:106–108CrossRefPubMed
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Wolff NC, Richardson JA, Egorin M, Ilaria RL (2003) The CNS is a sanctuary for leukemic cells in mice receiving imatinib mesylate (STI571) for Bcr/Abl-induced leukemia (prepublished online 20 February 2003, DOI 10.1182/blood-2002–10–3059). Blood 101:5010–5013CrossRefPubMed
Metadata
Title
CNS blast crisis of chronic myelogenous leukemia in a patient with a major cytogenetic response in bone marrow associated with low levels of imatinib mesylate and its N-desmethylated metabolite in cerebral spinal fluid
Authors
Martin Bornhauser
Andreas Jenke
Jens Freiberg-Richter
Jörgen Radke
Ulrich S. Schuler
Brigitte Mohr
Gerhard Ehninger
Eberhard Schleyer
Publication date
01-06-2004
Publisher
Springer-Verlag
Published in
Annals of Hematology / Issue 6/2004
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-003-0829-4

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