Problems of Radiation Medicine and Radiobiology

Dmytrenko I. V., Fedorenko V. G., Shlyakhtychenko T. Y., Sholoyko V. V., Lyubarets T. F., Malinkina T. V., Dmytrenko O. O., Balan V. V., Kravchenko S. M., Martina Z. V., Tovstogan A. O., Minchenko J. M., Dyagil I. S.

Assessment of response to imatinib therapy in patients with chronic myeloid leukemia with e13a2 and e14a2 transcripts of BCR/ABL1 gene

Objective. Assess the influence of e13a2 and e14a2 transcripts of BCR/ABL1 gene on the efficiency of imatinib therapy in patients with chronic myeloid leukemia.
Materials and methods. We examined 508 patients with the chronic phase of chronic myeloid leukemia without radiation in anamnesis as well as 13 patients with the similar diagnosis and with confirmed presence of radiation exposure due to the Chornobyl Nuclear Power Plant accident.
Results. No significant differences in hematologic parameters, rate of additional chromosomal aberrations and f variant translocations were observed between patients with е13а2 and е14а2 transcript. Cumulative probability of complete cytogenetic response did not differ in patients with е13а2 and е14а2 transcript and was 76 and 80 % respectively (р = 0.981). Median of achieving a complete cytogenetic response was 20 months in both patient groups. Significantly more patients with e14a2 transcript compared to patients with e13a2 achieved major molecular response by 12 month of therapy (61.5 % versus 23.0 %, p = 0.016). The higher incidence of deep molecular response by 24 month of therapy was revealed in this group (38.7 % versus 6.25 %, p = 0.018). The overall survival and progression-free survival rates were not statistically different between two groups with different transcripts. However, the rate of event-free survival was statistically lower for the patients with e13a2 transcript compared to the ones with e14a2 transcript (51 % versus 62.0 %, p = 0.039). The number of primary resistant patients was 40 % regardless of the transcript expressed. A significant prevalence in incidence either of lost complete cytogenetic response or failure of the major molecular response was shown in patients with e13a2 transcript compared to patients with e14a2 transcripts (43.5 % versus 24.8 %, p = 0.015).
Conclusion. Imatinib therapy is more effective for CML patients with e14a2 transcript compared to patients with e13a2 transcript expression. The transcript e13a2can be viewed as a adverse prognostic factor for imatinib therapy of chronic myeloid leukemia.

Key words: chronic myeloid leukemia, е13а2 and е14а2 transcripts, imatinib, cytogenetic and molecular responce, therapy efficeincy, ionizing radiation.

Problems of radiation medicine and radiobiology. 2015;20:328-340.