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Vol. 127, No. 4, 2012
Issue release date: May 2012
Section title: Original Paper
Acta Haematol 2012;127:221–227
(DOI:10.1159/000336244)

Correlation between Imatinib Trough Concentration and Efficacy in Chinese Chronic Myelocytic Leukemia Patients

Zhong J.-S.a · Meng F.-Y.b · Xu D.b · Zhou H.-S.b · Dai M.b
aDepartment of Haematology, Guangzhou Red Cross Hospital, and bDepartment of Haematology, Nanfang Hospital, Southern Medical University, Guangzhou, China

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 6/9/2011 5:23:54 PM
Accepted: 1/2/2012
Published online: 3/30/2012
Issue release date: May 2012

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 4

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: http://www.karger.com/AHA

Abstract

Background: Trough imatinib plasma concentration, intracellular drug levels and expression of drug transporters can be indicative of clinical responses in chronic myelocytic leukemia (CML) patients receiving imatinib. We aimed to determine plasma imatinib concentration, intracellular imatinib concentration, human organic cation transporter 1 (hOCT1) and adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) mRNA expression in bone marrow cells of CML patients in order to evaluate the potential usefulness of these measures as markers of imatinib efficacy and understand their clinical relationships. Methods: Eighty-four CML patients receiving imatinib treatment were included in this study. Imatinib trough concentration was determined by high-performance liquid chromatography-tandem mass spectrometry. Real-time quantitative PCR with a TaqMan probe was used to assess hOCT1 and ABCB1 mRNA expression in bone marrow cells. All patients were divided into the major molecular response (MMR), complete cytogenetic response (CCyR), partial cytogenetic response (PCyR) or drug-resistant groups according to their response. Results: The plasma imatinib trough concentration was significantly higher in the MMR group than in the PCyR (p = 0.002) or drug-resistant groups (p = 0.011). The plasma imatinib trough concentration was also significantly higher in the CCyR group than in the PCyR group (p = 0.027). There were no significant differences between the CCyR and MMR groups with regard to the plasma imatinib trough concentration (p = 0.136). The intracellular imatinib concentration in bone marrow cells was significantly higher in the CCyR group compared to the drug-resistant or PCyR groups (p = 0.013). The hOCT1 mRNA expression in bone marrow cells was significantly higher in the CCyR group than in the drug-resistant or PCyR groups (p = 0.036). The ABCB1 mRNA expression in bone marrow cells was significantly higher in the drug-resistant group than in the CCyR or PCyR groups (p = 0.013). Plasma imatinib trough concentration was positively correlated with α1-acid glycoprotein (r = 0.443, p < 0.001) or dose (r = 0.422, p < 0.001). Conclusions: Clinical responses in CML patients are correlated with both the plasma trough concentrations and intracellular levels of imatinib.

© 2012 S. Karger AG, Basel


  

Author Contacts

Fan-Yi Meng
Department of Haematology
Nanfang Hospital, Southern Medical University
Guangzhou 510515 (China)
Tel. +86 20 6164 1611, E-Mail mengfy1838@gmail.com

  

Article Information

Received: June 9, 2011
Accepted after revision: January 2, 2012
Published online: March 30, 2012
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 4, Number of References : 28

  

Publication Details

Acta Haematologica

Vol. 127, No. 4, Year 2012 (Cover Date: May 2012)

Journal Editor: Ben-Bassat I. (Qiryat-Ono)
ISSN: 0001-5792 (Print), eISSN: 1421-9662 (Online)

For additional information: http://www.karger.com/AHA


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 6/9/2011 5:23:54 PM
Accepted: 1/2/2012
Published online: 3/30/2012
Issue release date: May 2012

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 4

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: http://www.karger.com/AHA


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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