Problems of Radiation Medicine and Radiobiology

THE EFFICIENCY OF TYROSINE KINASE INHIBITOR THERAPY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA EXPOSED TO IONIZING RADIATION DUE TO THE CHORNOBYL NUCLEAR POWER PLANT ACCIDENT

I. V. Dmytrenko, V. G. Fedorenko, T. Y. Shlyakhtychenko, V. V. Sholoyko, T. F. Lyubarets, T. V. Malinkina, O. O. Dmytrenko, V. V. Balan, S. M. Kravchenko, Z. V. Martina, A. O. Tovstogan, J. M. Minchenko, I. S. Dyagil
State Institution “National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine”, Melnykov str., 53, Kyiv, 04050, Ukraine

Objective. To study the efficiency of tyrosine kinase inhibitors (TKI) therapy in patients with chronic myeloid leukemia (CML) exposed to ionizing radiation due to the Chornobyl NPP accident, based on the data of cytogenetic and molecular monitoring.
Material and methods. 29 CML patients with confirmed radiation exposure due to Chornobyl NPP accident were examined. Of these, 20 patients were treated with imatinib; 103 patients with CML without radiation history treated with TKI were a comparison group. Cytogenetic and molecular genetic disturbances before and on the different stage of TKI therapy were analysed.
Results. Additional chromosomal abnormalities as well as special pattern of BCR/ABL transcripts were not revealed in CML patients exposed to ionizing radiation. Complete cytogenetic response (CCR) was shown in 50 and 48.5 % of patients from study and comparison group, respectively. Major molecular response (MMR) was achieved in 20 % of patients with radiation exposure in anamnesis and in 27.6 % of patients from comparison group. The vast majority of CCR and MMR was reached in patients with the pretreatment term up to 6 months, when imatinib was used as a
first line therapy. There were less cases of primary imatinib resistance in the same group of patients. In CML patients who had a history of radiation exposure, secondary resistance developed more frequently than in the comparison group and was 25 %.
Conclusion. Laboratory monitoring based on the registration of CCR and MMR demonstrated high efficiency of TKI in the CML treatment of patients, exposed due to Chornobyl accident. Extension of pretreatment term leads to the loss of TKI therapy efficiency and increases the likelihood of primary resistance. CML patients exposed to ionizing radiation develop secondary resistence more often than CML patients without radiation exposure in anamnesis.

Key words: chronic myeloid leukemia, ionizing radiation, tyrosine kinase inhibitors, cytogenetic and molecular response, treatment efficiency.

Problems of radiation medicine and radiobiology. 2014;19:241-255.