Prognostic value of early reduction of BCR/ABL1 gene expression in criteria of deep molecular response on imatynib therapy in patients with chronic myeloid leukemia

Authors

  • І. В. Дмитренко State Institution "National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine"

DOI:

https://doi.org/10.18372/2306-6407.1.12851

Keywords:

chronic myeloid leukemia, BCR/ABL1, deep molecular response, tyrosine kinase inhibitors, prognostic factors

Abstract

Achieving a deep molecular response (MR4) is a prerequisite for imatinib therapy discontinuation in patients with chronic myeloid leukemia (CML). 313 patients with a chronic phase of CML at the age from 18 to 80 years (Me = 42 years) were examined to determine the range of informative early criteria that will allow to select patients with a high probability of MR4 by 24 months of imatinib therapy. The prediction value of the BCR/ABL1 transcript level at 3 months and 6 months of imatinib therapy and initial clinical-laboratory and demographic factors were analyzed (age, sex, risk group for Sokal, Hasford, EUTOS and ELTS systems, duration of therapy before imatinib and BCR/ABL1 transcript type). By multivariate analysis, the type of BCR/ABL1 transcript (p = 0.045) and the duration of therapy before imatinib (p = 0.006) were the initial independent predictors of a deep molecular response at 24 months. The BCR/ABL1 transcript level at 3 months and 6 months were also significantly associated with the reduction of the tumor clone to the level of MR4 at 24 months of therapy. The threshold ​​for the BCR/ABL1 transcript level was determined to be 3.7 % at 3 months and BCR/ABL1 = 0.4 % at 6 months. The excess of these threshold increased the risk of deep molecular response failure at 24 months. It is shown that the inclusion the BCR/ABL1 < 3.7 % at 3 months as an additional factor significantly increased the accuracy of prognosis the MR4 at 24 months  and eliminated the importance of other prognostic factors.

Author Biography

І. В. Дмитренко, State Institution "National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine"

candidate of biological sciences, senior researcher, laboratory of immunogenetics, department of Hematology and transplantology

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Published

2018-06-27

Issue

Section

Experimental articles