Molecular control of treatment with imatinib in patients with chronic myeloif leukemia

G. Balatzenko, M. Guenova, V. Hristchev, A. Lilova, G. Mihailov, J. Grudeva-Popova, K. Alexandrova, A. Antonov, I. Micheva

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Résumé

Quantitative assessment of BCR-ABL transcripts is a common approach for therapeutic response monitoring in chronic myeloid leukemia (CML). In our country, evaluation of the clinical relevance has not been conducted so far. Therefore, we analysed 93 CML patients (pts) (43 females; 50 males) at different disease stages, at different time-points during the treatment with Imatinib (IM) as a second-line therapy. A control group of 10 pts in chronic phase (CP) at the time of diagnosis was also included. Detection and quantitative assessment of BCR-ABL transcripts were performed using nested RT-PCR (N-RT-PCR) and quantitative RT-PCR (Q-RT-PCR). By applying N-RT-PCR, 2 groups were clearly distinguished: (group I) pts with a distinct reduction of BCR-ABL transcripts, including cases with a negative BCR-ABL result (n = 56; 60,2%); and (group II) pts without visible molecular response (MR) (n = 37; 39,8%), including 8 (8.6%) cases with blast crisis (BC). Using Q-RT-PCR, the value of BCR-ABL/ABL ratio was determined. The mean ratio was 71.2 ± 23.2% in the control group of pts in CP prior therapy. In group I, BCR-ABL/ABL was significantly lower (mean = 0.58 ± 1.2%), including 31 (33,3%) pts with values < 0.1% [Major MR (MMR)], 5 (5.4%) - with no detectable BCR-ABL by both methods [Complete MR (CMR)], and 21 pts with BCR-ABL/ABL levels between 5.0% and 0.22%. In the first 18 months of treatment, MR was found in 7/37 (18.9%) pts, while after the 18th month - in 29/56 (51.8%), including 5 cases with CMR (p = 0.002). In group II, the mean BCR-ABL/ABL value in BC samples was significantly higher in comparison to CP (102.6 ± 10.3% vs 71.2 ± 23.2%). In contrast, patients with hematological and/or cytogenetic response in the same group were characterised by significantly lower values (mean = 30.0 ± 15.6%). In conclusion, our results define the molecular monitoring as a key element for the optimization of therapy in the individual patient which is in agreement with the recent recognition of MMR as a major prognostic factor that correlates with an extremely low risk of CML progression.

langue originaleAnglais
Pages (de - à)74-80
Nombre de pages7
journalClinical and Transfusion Haematology
Volume46
Numéro de publication1-2
étatPublié - 1 déc. 2010
Modification externeOui

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