efficacy and pharmacologic data of second-generation tyrosine kinase inhibitor nilotinib in bcr-abl-positive leukemia patients with central nervous system relapse after allogeneic stem cell transplantation

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2014
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Abstract
Central nervous system (CNS) involvement is a severe complication of BCR-ABL-positive leukemia after allogenic stem cell transplantation (alloSCT) associated with fatal outcome. Although second-generation tyrosine-kinase inhibitors (TKI) such as nilotinib have shown activity in systemic BCR-ABL+ disease, little data exists on their penetration and efficacy within the CNS. Four patients (3 male, 1 female; age 15–49) with meningeal relapse after alloSCT and subsequent treatment with nilotinib were identified. A total of 17 cerebrospinal fluid (csf) and serum samples were assessed for nilotinib concentration and patient outcome was recorded. Nilotinib concentrations showed a low median csf/plasma ratio of 0.53% (range 0.23–1.5%), yet pronounced clinical efficacy was observed with long-lasting responses (>1 year) in three patients. Comparison with historical data showed a trend towards superior efficacy of nilotinib versus imatinib. Despite poor csf penetration, nilotinib showed significant clinical activity in CNS relapse of BCR-ABL+ leukemias. As nilotinib has a high protein-binding affinity, the low-protein concentration in csf could translate into a relatively higher amount of free and therefore active nilotinib in csf as compared to blood, possibly explaining the observed efficacy. Thus, treatment with a 2nd generation TKI warrants further investigation and should be considered in cases of CNS relapse of BCR-ABL-positive leukemia after alloSCT.
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reinwald2014biomedefficacy Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Mark Reinwald, Eberhard Schleyer, Philipp Kiewe, Igor Wolfgang Blau, Thomas Burmeister, Stefan Pursche, Martin Neumann, Michael Notter, Eckhard Thiel, Wolf-Karsten Hofmann, Hans-Jochem Kolb, Stefan Burdach, Hans-Ulrich Bender
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Journal spectrochimica acta - part a: molecular and biomolecular spectroscopy
Year 2014
DOI
10.1155/2014/637059
URL
http://dx.doi.org/10.1155/2014/637059
Keywords
Medicine

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