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Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon α/ara-C

We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphase...

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Main Authors: Müller, Martin Christian (Author) , Gattermann, N. (Author) , Lahaye, T. (Author) , Deininger, M. W. N. (Author) , Berndt, A. (Author) , Frühauf, Stefan (Author) , Neubauer, A. (Author) , Fischer, Thomas (Author) , Hossfeld, D. K. (Author) , Schneller, F. (Author) , Krause, S. W. (Author) , Nerl, C. (Author) , Sayer, H. G. (Author) , Ottmann, O. G. (Author) , Waller, C. (Author) , Aulitzky, W. (Author) , Coutre, P. le (Author) , Freund, M. (Author) , Merx, Kirsten (Author) , Paschka, Peter (Author) , König, H. (Author) , Kreil, Sebastian (Author) , Berger, Ute (Author) , Gschaidmeier, Harald (Author) , Hehlmann, Rüdiger (Author) , Hochhaus, Andreas (Author)
Format: Article (Journal)
Language:English
Published: 02 October 2003
In: Leukemia
Year: 2003, Volume: 17, Issue: 12, Pages: 2392-2400
ISSN:1476-5551
DOI:10.1038/sj.leu.2403157
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.leu.2403157
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/2403157
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Author Notes:M. C. Müller, N. Gattermann, T. Lahaye, M. W. N. Deininger, A. Berndt, S. Fruehauf, A. Neubauer, T. Fischer, D. K. Hossfeld, F. Schneller, S. W. Krause, C. Nerl, H. G. Sayer, O. G. Ottmann, C. Waller, W. Aulitzky, P. le Coutre, M. Freund, K. Merx, P. Paschka, H. König, S. Kreil, U. Berger, H. Gschaidmeier, R. Hehlmann and A. Hochhaus
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Summary:We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 cases by real-time PCR, but in only four patients by nested PCR. Median best response in patients with relapse after CCR was 0.24% (n=3) as compared to 0.029% in patients with continuous remission (n=52, P=0.029). We conclude that (i) treatment with imatinib in newly diagnosed CML patients is associated with a rapid decrease of BCR-ABL transcript levels; (ii) nested PCR may reveal residual BCR-ABL transcripts in samples that are negative by real-time PCR; (iii) BCR-ABL transcript levels parallel cytogenetic response, and (iv) imatinib is superior to IFN/Ara-C in terms of the speed and degree of molecular responses, but residual disease is rarely eliminated.
Item Description:Gesehen am 13.05.2022
Physical Description:Online Resource
ISSN:1476-5551
DOI:10.1038/sj.leu.2403157

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