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

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. PaschkaH. König, S. Kreil, U. Berger, H. Gschaidmeier, R. Hehlmann, Andreas Hochhaus

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105 Scopus citations

Abstract

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 beat 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.

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Keywords

  • BCR-ABL
  • Chronic myelogenous leukemia
  • Imatinib
  • Interferon alpha
  • Quantitative PCR

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Müller, M. C., Gattermann, N., Lahaye, T., Deininger, M. W. N., Berndt, A., Fruehauf, S., Neubauer, A., Fischer, T., Hossfeld, D. K., Schneller, F., Krause, S. W., Nerl, C., Sayer, H. G., Ottmann, O. G., Waller, C., Aulitzky, W., le Coutre, P., Freund, M., Merx, K., ... Hochhaus, A. (2003). Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon α/ara-C. Leukemia, 17(12), 2392-2400. https://doi.org/10.1038/sj.leu.2403157