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Imatinib in Philadelphia chromosome-positive chronic phase CML patients: molecular and cytogenetic response rates and prediction of clinical outcome

Item Type:Article
Title:Imatinib in Philadelphia chromosome-positive chronic phase CML patients: molecular and cytogenetic response rates and prediction of clinical outcome
Creators Name:Le Coutre, P. and Kreuzer, K.A. and Na, I.K. and Schwarz, M. and Lupberger, J. and Holdhoff, M. and Baskaynak, G. and Gschaidmeier, H. and Platzbecker, U. and Ehninger, G. and Prejzner, W. and Huhn, D. and Schmidt, C.A.
Abstract:Previous clinical trials with the tyrosine kinase inhibitor imatinib in chronic-phase Philadelphia chromosome-positive chronic myelogenous leukemia (CML) resulted in 95% of hematologic and 60% major cytogenetic remissions in patients who failed a previous interferon-alpha-containing regimen. In an identical clinical trial setting with 39 chronic-phase CML patients we achieved comparable cytogenetic response rates after a median follow up of 30.1 weeks, with an almost identical toxicity profile. In order to identify predictive markers for the therapeutical use of imatinib, we monitored apart from standard hematology parameters bcr/abl fusion transcripts by quantitative real-time fluorescence RT-PCR. As previous investigations demonstrated that the plasma protein alpha-1 acid glycoprotein might inactivate circulating levels of free imatinib by protein binding with high affinity, we assessed plasma alpha-1 acid glycoprotein concentrations in our study cohort as well. Median bcr/abl fusion transcripts declined gradually over the entire treatment period and became significantly lowered at month 3 after initiation of imatinib therapy. Further, we observed elevated pretreatment levels of alpha-1 acid glycoprotein in patients who relapsed with leukemia, whereas initial bcr/abl mRNA copy numbers were not of predictive value. In addition, we provide data showing molecular response to this therapy in the vast majority of patients. Finally, our results support the hypothesis, that initially elevated plasma levels of alpha-1 acid glycoprotein might serve as a predictive marker for the clinical outcome of treatment with imatinib.
Keywords:Antineoplastic Agents, Bcr-Abl Fusion Proteins, Bcr-Abl Positive Chronic Myelogenous Leukemia, Biological Markers, Cytogenetic Analysis, Messenger RNA, Molecular Diagnostic Techniques, Orosomucoid, Piperazines, Prognosis, Pyrimidines, Recurrence, Remission Induction, Time Factors
Source:American Journal of Hematology
ISSN:0361-8609
Publisher:Wiley (U.S.A.)
Volume:73
Number:4
Page Range:249-255
Date:August 2003
Official Publication:https://doi.org/10.1002/ajh.10364
PubMed:View item in PubMed

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