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
State Institution National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine, Melnykov str., 53, Kyiv, 04050, Ukraine.
Probl Radiac Med Radiobiol. 2014 Sep;19:241-55.
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.
目的。基于细胞遗传学和分子监测数据，研究酪氨酸激酶抑制剂（TKI）疗法对因切尔诺贝利核电站事故遭受电离辐射的慢性髓性白血病（CML）患者的疗效。材料与方法。对29例因切尔诺贝利核电站事故确诊有辐射暴露史的CML患者进行检查。其中，20例患者接受伊马替尼治疗；103例无辐射史的CML患者接受TKI治疗作为对照组。分析TKI治疗前及不同阶段的细胞遗传学和分子遗传学紊乱情况。结果。在遭受电离辐射的CML患者中未发现额外的染色体异常以及BCR/ABL转录本的特殊模式。研究组和对照组分别有50%和48.5%的患者出现完全细胞遗传学缓解（CCR）。有辐射暴露史的患者中20%达到主要分子缓解（MMR），对照组为27.6%。当伊马替尼作为一线治疗药物时，绝大多数CCR和MMR在预处理期达6个月的患者中实现。同一组患者中伊马替尼原发性耐药的病例较少。有辐射暴露史的CML患者中，继发性耐药的发生频率高于对照组，为25%。结论。基于CCR和MMR记录的实验室监测表明，TKI对因切尔诺贝利事故而暴露的CML患者治疗具有高效性。预处理期延长会导致TKI治疗效率降低，并增加原发性耐药的可能性。与无辐射暴露史的CML患者相比，遭受电离辐射的CML患者更常出现继发性耐药。
