CHARACTERISTICS OF CLONES WITH ADDITIONAL CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA AND THEIR IMPACT ON THE IMATINIB THERAPY EFFICACY
Dmytrenko I.V., Minchenko Zh.M., Fedorenko V.G., Dyagil I.S.
Objective: to evaluate the impact of various additional chromosomal abnormalities (ACA) on the chronic myeloid leukemia (CML) course and the imatinib therapy effficacy. Object and Methods: the study involved 45 CML patients in chronic phase with ACA at the time of diagnosis or during imatinib therapy. Patients were selected from a general group of CML patients enrolled in cytogenetic analysis at the National Radiation Medicine Center of the National Academy of Medical Sciences of Ukraine for the period 2008 to 2019. All patients received imatinib. The probability of overall survival (OS), progression-free survival (PFS), and event free survival (EFS) were analyzed from the moment of the ACA appearance to the occurrence of each event. Results: a total of 54 ACA were detected in 45 CML patients. By type of formation ACA was divided into quantitative (16 aberrations), structural (10 aberrations) and doubling of the Ph-chromosome der(22)t(9;22)(q34;q11) (28 cases). Five patients had more than one ACA (complex karyotype). ACA from the adverse prognosis group according to Wang et al. and the presence of isochromosome 17 over the long arm demonstrated significant worse prognosis PFS (p = 0.002 and p = 0.016, respectively) and OS (p = 0.048 and p = 0.001, respectively). The presence of more than one additional chromosomal abnormality also significantly impaired the likelihood of disease progression (p = 0.029). Patients with an additional Ph-chromosome and an additional chromosome 8 both at diagnosis and during imatinib therapy had a risk of disease progression no greater than patients with other ACA. Conclusion: finding ACAs that cause aggressive disease course and rapid progression will allow to identify CML patients for which changes in therapy are required.
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