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  • Title: 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.
    Author: Dmytrenko IV, Fedorenko VG, Shlyakhtychenko TY, Sholoyko VV, Lyubarets TF, Malinkina TV, Dmytrenko OO, Balan VV, Kravchenko SM, Martina ZV, Tovstogan AO, Minchenko JM, Dyagil IS.
    Journal: Probl Radiac Med Radiobiol; 2014 Sep; 19():241-55. PubMed ID: 25536562.
    Abstract:
    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. Meta. Vyvchyty efektyvnist' terapii' ingibitoramy tyrozynkinaz (ITK) pacijentiv z hronichnoju mijeloi'dnoju lejkemijeju (HML), jaki zaznaly dii' ionizujuchogo vyprominjuvannja vnaslidok avarii' na Chornobyl's'kij AES, na pidstavi danyh cytogenetychnogo i molekuljarnogo monitoryngu. Materialy i metody. Obstezheno 29 hvoryh na HML, u jakyh bulo dokumental'no pidtverzheno najavnist' radiacijnogo vplyvu vnaslidok avarii' na ChAES. Z nyh 20 pacijentiv otrymuvaly terapiju imatynibom. Grupu porivnjannnja sklaly 103 pacijenty z HML bez radiacijnogo anamnezu, jaki otrymuvaly terapiju ITK. Doslidzhuvaly cytogenetychni ta molekuljarno-genetychni porushennja v debjuti zahvorjuvannja ta na riznyh etapah terapii' ITK. Rezul'taty. U pacijentiv z HML, shho zaznaly vplyvu ionizujuchogo oprominennja, v debjuti zahvorjuvannja ne bulo vyjavleno zbil'shennja chastoty pojavy dodatkovyh hromosomnyh porushen' ta osoblyvostej rozpodilu za typamy BCR/ABL transkryptiv. Povnu cytogenetychnu vidpovid' (PCV) rejestruvaly u 50 ta 48,5 % pacijentiv v grupi sposterezhennja ta kontrol'nij grupi, vidpovidno. Velyku molekuljarnu vidpovid' (VMV) vyznachaly u 20 % hvoryh na HML, jaki maly v anamnezi radiacijne oprominennja i u 27,6 % vypadkiv pacijentiv grupy porivnjannja. Najkrashhi rezul'taty dosjagnennja PCV i VMV vyjavleni u pacijentiv z terminom peredlikovanosti do 6 mis, u jakyh imatynib vykorystovuvavsja jak terapija pershoi' linii'. U pacijentiv z HML (oprominenyh i neoprominenyh), jakym imatynib bulo pryznacheno ne piznishe 6 mis vid pochatku zahvorjuvannja, vyjavleno virogidno menshu kil'kist' vypadkiv pervynnoi' rezystentnosti do imatynibu. U pacijentiv z HML, jaki v anamnezi maly radiacijnyj vplyv, vtorynna rezystentnist' rozvyvalasja chastishe porivnjano z grupoju porivnjannja i stanovyla 25 %. Vysnovky. Kliniko-laboratornyj monitoryng z urahuvannjam chastoty dosjagnennja PCV i VMV pokazav vysoku efektyvnist' ITK v likuvanni hvoryh na HML, jaki zaznaly vplyvu ionizujuchogo vyprominjuvannja vnaslidok avarii' na ChAES. Podovzhennja stroku peredlikovanosti pryzvodyt' do znyzhennja efektyvnosti terapii' ITK ta pidvyshhennja jmovirnosti rozvytku pervynnoi' rezystentnosti. Pacijenty z HML, jaki v anamnezi majut' radiacijnyj vplyv, harakteryzujut'sja bil'sh chastym rozvytkom vtorynnoi' rezystentnosti.
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