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

Philipp Le Coutre, Karl Anton Kreuzer, Il Kang Na, Michaela Schwarz, Joachim Lupberger, Matthias Holdhoff, Gökben Baskaynak, Harald Gschaidmeier, Uwe Platzbecker, Gerhard Ehninger, Witold Prejzner, Dieter Huhn, Christian A. Schmidt

Research output: Contribution to journalArticle

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-α-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 α-1 acid glycoprotein might inactivate circulating levels of free imatinib by protein binding with high affinity, we assessed plasma α-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 α-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 α-1 acid glycoprotein might serve as a predictive marker for the clinical outcome of treatment with imatinib.

Original languageEnglish (US)
Pages (from-to)249-255
Number of pages7
JournalAmerican Journal of Hematology
Volume73
Issue number4
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Philadelphia Chromosome
Cytogenetics
Glycoproteins
Acids
Clinical Trials
Hematology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein Binding
Protein-Tyrosine Kinases
Interferons
Blood Proteins
Leukemia
Cohort Studies
Therapeutics
Biomarkers
Fluorescence
Imatinib Mesylate
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Hematology

Cite this

Imatinib in Philadelphia chromosome-positive chronic phase CML patients : Molecular and cytogenetic response rates and prediction of clinical outcome. / Le Coutre, Philipp; Kreuzer, Karl Anton; Na, Il Kang; Schwarz, Michaela; Lupberger, Joachim; Holdhoff, Matthias; Baskaynak, Gökben; Gschaidmeier, Harald; Platzbecker, Uwe; Ehninger, Gerhard; Prejzner, Witold; Huhn, Dieter; Schmidt, Christian A.

In: American Journal of Hematology, Vol. 73, No. 4, 01.08.2003, p. 249-255.

Research output: Contribution to journalArticle

Le Coutre, P, Kreuzer, KA, Na, IK, Schwarz, M, Lupberger, J, Holdhoff, M, Baskaynak, G, Gschaidmeier, H, Platzbecker, U, Ehninger, G, Prejzner, W, Huhn, D & Schmidt, CA 2003, 'Imatinib in Philadelphia chromosome-positive chronic phase CML patients: Molecular and cytogenetic response rates and prediction of clinical outcome', American Journal of Hematology, vol. 73, no. 4, pp. 249-255. https://doi.org/10.1002/ajh.10364
Le Coutre, Philipp ; Kreuzer, Karl Anton ; Na, Il Kang ; Schwarz, Michaela ; Lupberger, Joachim ; Holdhoff, Matthias ; Baskaynak, Gökben ; Gschaidmeier, Harald ; Platzbecker, Uwe ; Ehninger, Gerhard ; Prejzner, Witold ; Huhn, Dieter ; Schmidt, Christian A. / Imatinib in Philadelphia chromosome-positive chronic phase CML patients : Molecular and cytogenetic response rates and prediction of clinical outcome. In: American Journal of Hematology. 2003 ; Vol. 73, No. 4. pp. 249-255.
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