cardiotomskСибирский журнал клинической и экспериментальной медициныSiberian Journal of Clinical and Experimental Medicine2713-29272713-265XTSU publishing10.29001/2073-8552-2017-32-2-31-35cardiotomsk-294Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESСЕГОДНЯШНИЙ ДЕНЬ В ТЕРАПИИ ХРОНИЧЕСКОГО МИЕЛОЛЕЙКОЗА: РЕЗУЛЬТАТЫ И СЛОЖНОСТИTODAY IN THE TREATMENT OF CHRONIC MYELOID LEUKEMIA: RESULTS AND DIFFICULTYЛямкинаА. С.LyamkinaA. S.

канд. мед. наук, доцент кафедры терапии, гематологии и трансфузиологии  ФГБОУ ВО “Новосибирский государственный медицинский университет”  Минздрава России

Адрес: 630091, г. Новосибирск, Красный проспект, 52

anna_lyam@mail.ruПоспеловаТ. И.PospelovaT. I.

докт. мед. наук, проректор по научной работе, заведующая кафедрой терапии, гематологии и трансфузиологии ФПК и ППВ ФГБОУ ВО  “Новосибирский государственный медицинский университет” Минздрава  России, заслуженный врач РФ

Адрес: 630091, г. Новосибирск, ул. Красный проспект, 52

post_gem@mail.ruМасловаЛ. М.MaslovaL. M.

заведующая гематологическим консультационным центром ГБУЗ НСО “ГКБ № 2”, г. Новосибирск

Адрес: 630051, г. Новосибирск, ул. Ползунова, 21

post_gem@mail.ruНечунаеваИ. Н.NechunaevaI. N.

канд. мед. наук, зав. отделением гематологии ГБУЗ НСО “Городская клиническая больница № 2”, г. Новосибирск

nech_ir@mail.ruКолесниковаМ. А.KolesnikovaM. A.

аспирант кафедры терапии, гематологии и трансфузиологии ФПК и ППВ ФГБОУ ВО “Новосибирский государственный медицинский университет” Минздрава России

Адрес: 630091, г. Новосибирск, Красный проспект, 52

marija.com.ka@mail.ruМезитЕ. В.MezitE. V.

клинический ординатор кафедры терапии, гематологии и трансфузиологии ФПК и ППВ ФГБОУ ВО “Новосибирский государственный медицинский университет” Минздрава России

post_gem@mail.ruФГБОУ ВО “Новосибирский государственный медицинский университет” Минздрава РоссииРоссияNovosibirsk State Medical UniversityRussian FederationГБУЗ НСО “Городская клиническая больница № 2”РоссияCity Clinical Hospital No. 2Russian Federation2017061020173223135Copyright © Лямкина А.С., Поспелова Т.И., Маслова Л.М., Нечунаева И.Н., Колесникова М.А., Мезит Е.В., 20172017Лямкина А.С., Поспелова Т.И., Маслова Л.М., Нечунаева И.Н., Колесникова М.А., Мезит Е.В.Lyamkina A.S., Pospelova T.I., Maslova L.M., Nechunaeva I.N., Kolesnikova M.A., Mezit E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sibjcem.ru/jour/article/view/294

Проанализированы результаты терапии хронического миелолейкоза в группе больных (78 человек), получавших терапию иматинибом более 12 месяцев. В результате проводимой терапии полная клинико-гематологическая ремиссия достигнута у 98,7% больных (77 человек). Полный цитогенетический ответ (ph+<0%) – у 60 (76,9%), большой молекулярный ответ (уровень гена BCR/ABL <0,01%) – у 58,9% (46 человек). Первичная резистентность к иматинибу наблюдалась у 12 человек (15,4%), вторичная (четверо больных утратили ПКГО и ПЦО, двое – ПЦО и БМО) – у 6 человек (7,7%). Из них 9 человек (10,8%) были переведены на терапию ингибиторами тирозинкиназы 2 поколения (нилотиниб, дазатиниб). На фоне проводимой терапии ингибиторами ИТК 2 поколения у 8 человек сохраняется ПКГО (88,9%), у 5 – достигнут ПЦО (55,5%) и у 4 получен БМО (44,4%). В целом при терапии ИТК I и II поколения ПЦО достигнут у 83,3% пациентов, БМО – у 64,1% обследованных. Проведена оценка общей выживаемости (ОВ) больных при терапии ИТК, медиана ОВ не достигнута, 5-летняя ОВ составила 90%, 10-летняя ОВ составила более 77%, расчетная 15-летняя ОВ – более 60%.

We have analyzed the therapy outcomes of chronic myeloid leukemia of patients, received imatinib treatment for more than 12 month. Complete hematologic response (CHO) is attained in 98.7% cases (77 patients), complete cytogenetic response (CCR) (ph+<0%) – in 76.9% cases (60 patients), major molecular response (MMR) – in 58.9% cases (46 patients). The primary resistance to imatinib is observed in 15.4% cases (12 patients), secondary – in 7.7% cases (6 patients – 4 patients have lost the complete hematologic response (CHO) and complete cytogenetic response(CCR) and 2 patients have lost the complete cytogenetic response(CCR) and major molecular response (MMR)). The nine patients of those, who have primary or secondary resistance to imatinib have been treated with second-generation tyrosine kinase inhibitors (nilotinib, dasatinib) and in 88.9% cases (8 patients) the complete hematologic response (CCR) have been obtained, 5 patients (55.5%) have attained the complete cytogenetic response (CCR) and 4 patients (44.4%) have achieved the major molecular response (MMR). Among all those patients, who have been treated with I and II generations tyrosine kinase inhibitors, 83.3% patients have attained complete cytogenetic response (CCR), 64.1% – major molecular response. We have estimated overall survival (OS) analysis and obtained following results: the median of OS have not been achieved, 5-years OS rate is estimated as 90%, 10-years OS rate – more than 77%, calculated 15-years OS – more than 60%.

хронический миелолейкозполный цитогенетический ответбольшой молекулярный ответвыживаемость.chronic myeloid leukemiacomplete cytogenetic responsemajor molecular responsesurvivalReferencesВиноградова О.Ю., Куликов С.М., Куцев С.И. и др. Проблемы организации лечения хронического миелолейкоза в России // Клиническая онкогематология. Фундаментальные исследования и клиническая практика. – 2011. – Т. 4, № 4. – С. 292–297.Виноградова О.Ю., Куликов С.М., Куцев С.И. и др. Проблемы организации лечения хронического миелолейкоза в России // Клиническая онкогематология. Фундаментальные исследования и клиническая практика. – 2011. – Т. 4, № 4. – С. 292–297.Зарицкий А.Ю., Ломаиа Е.Г., Виноградова О.Ю., и др. Факторы прогноза при терапии иматиниба мезилатом у больных в хронической фазе Ph-позитивного хронического миелолейкоза: данные многоцентрового нерандомизированного исследования вЗарицкий А.Ю., Ломаиа Е.Г., Виноградова О.Ю., и др. Факторы прогноза при терапии иматиниба мезилатом у больных в хронической фазе Ph-позитивного хронического миелолейкоза: данные многоцентрового нерандомизированного исследования вРоссии // Терапевтический архив. – 2007. – Т. 79, № 8. – С. 17–22.России // Терапевтический архив. – 2007. – Т. 79, № 8. – С. 17–22.Зарицкий А.Ю., Ломайа Э.Г., Виноградова О.Ю. и др. Результаты многоцентрового исследования терапии Гливеком больных хроническим миелолейкозом в хронической фазе // Гематология и трансфузиология. – 2007. – Т. 52, № 2. – С. 13–17.Зарицкий А.Ю., Ломайа Э.Г., Виноградова О.Ю. и др. Результаты многоцентрового исследования терапии Гливеком больных хроническим миелолейкозом в хронической фазе // Гематология и трансфузиология. – 2007. – Т. 52, № 2. – С. 13–17.Ломаия Э.Г., Зарицкий А.Ю. Нилотиниб – новый этап успеха в терапии хронического миелолейкоза // Современная онкология, экстравыпуск. – С. 7–12.Ломаия Э.Г., Зарицкий А.Ю. Нилотиниб – новый этап успеха в терапии хронического миелолейкоза // Современная онкология, экстравыпуск. – С. 7–12.Лорие С.С., Курова Е.С., Семочкин С.В., Туркина А.Г. и др. Эффективность и безопасность терапии иматиниб мезилатом (Гливеком) больных хроническим миелолейкозом в фазе акселерации // Вопросы гематологии/онкологии и иммунопатологии в педиатрии. – 2002. – Т. 1, № 2. – С. 66– 67.Лорие С.С., Курова Е.С., Семочкин С.В., Туркина А.Г. и др. Эффективность и безопасность терапии иматиниб мезилатом (Гливеком) больных хроническим миелолейкозом в фазе акселерации // Вопросы гематологии/онкологии и иммунопатологии в педиатрии. – 2002. – Т. 1, № 2. – С. 66– 67.Мартынкевич И.С., Мартыненко Л.С., Иванова М.П., и др. Дополнительные хромосомные аберрации у пациентов с хроническим миелолейкозом // Гематология и трансфузиология. – 2007. – Т. 52, № 2. – С. 28–35.Мартынкевич И.С., Мартыненко Л.С., Иванова М.П., и др. Дополнительные хромосомные аберрации у пациентов с хроническим миелолейкозом // Гематология и трансфузиология. – 2007. – Т. 52, № 2. – С. 28–35.Туркина А.Г., Хорошко Н.Д. Практические рекомендации по лечению больных хроническим миелолейкозом. – М., 2005. – С. 4–5.Туркина А.Г., Хорошко Н.Д. Практические рекомендации по лечению больных хроническим миелолейкозом. – М., 2005. – С. 4–5.Туркина А.Г., Хорошко Н.Д. Практические рекомендации по лечению больных хроническим миелолейкозом. – М., 2008. – С. 3–6.Туркина А.Г., Хорошко Н.Д. Практические рекомендации по лечению больных хроническим миелолейкозом. – М., 2008. – С. 3–6.Туркина А.Г., Хорошко Н.Д., Дружкова Г.А. и др. Эффективность терапии иматиниба мезилатом (Гливеком) в хронической фазе миелолейкоза // Терапевтический архив. –2003. – Т.75, № 8. – С. 62–67.Туркина А.Г., Хорошко Н.Д., Дружкова Г.А. и др. Эффективность терапии иматиниба мезилатом (Гливеком) в хронической фазе миелолейкоза // Терапевтический архив. –2003. – Т.75, № 8. – С. 62–67.Apperley J.F. Part I: Mechanisms of resistance to imatinib in chronic myeloid leukemia // Lancet Oncol. – 2007. – Vol. 8. – P. 1018–1029.Apperley J.F. Part I: Mechanisms of resistance to imatinib in chronic myeloid leukemia // Lancet Oncol. – 2007. – Vol. 8. – P. 1018–1029.Apperley J.F. Part II: Management of resistance to imatinib in chronic myeloid leukemia // Lancet Oncol. – 2007. – Vol. 8. – P. 1116–1129.Apperley J.F. Part II: Management of resistance to imatinib in chronic myeloid leukemia // Lancet Oncol. – 2007. – Vol. 8. – P. 1116–1129.Baccarani M., Saglio G., Goldman J. et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet // Blood. – 2006, Sep. 15. – Vol. 108 (6). – P. 1809–1820.Baccarani M., Saglio G., Goldman J. et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet // Blood. – 2006, Sep. 15. – Vol. 108 (6). – P. 1809–1820.Branford S., Cross N.C.P., Hochhaus A. et al. Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukemia // Leukemia. – 2006. – Vol. 20 (11). – P. 1925–1930.Branford S., Cross N.C.P., Hochhaus A. et al. Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukemia // Leukemia. – 2006. – Vol. 20 (11). – P. 1925–1930.Branford S., Rudzki Z., Parkinson I. et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations // Blood. – 2004. – Vol. 104. – P. 2926–2932.Branford S., Rudzki Z., Parkinson I. et al. Real-time quantitative PCR analysis can be used as a primary screen to identify patients with CML treated with imatinib who have BCR-ABL kinase domain mutations // Blood. – 2004. – Vol. 104. – P. 2926–2932.Burgess M., Skaggs B.J., Shah N.P. et al. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance // PNAS. – 2005. – Vol. 102. – P. 3395–3400.Burgess M., Skaggs B.J., Shah N.P. et al. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance // PNAS. – 2005. – Vol. 102. – P. 3395–3400.Deininger M.W. Nilotinib // Clin Cancer Res. – 2008. – Vol. 14. – P. 4027–4031.Deininger M.W. Nilotinib // Clin Cancer Res. – 2008. – Vol. 14. – P. 4027–4031.Druker B.J., Talpaz M., Resta D.J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia // N. Engl. J. Med. – 2001. – Vol. 344. – P. 1031–1037.Druker B.J., Talpaz M., Resta D.J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia // N. Engl. J. Med. – 2001. – Vol. 344. – P. 1031–1037.Druker B.J., Tamura S., Buchdunger E. et al. Effects of a selective inhibitor of the ABL tyrosine kinase on the growth of BCR-ABL- positive cells // Nat. Med. – 1996. – Vol. 2. – P. 561–566.Druker B.J., Tamura S., Buchdunger E. et al. Effects of a selective inhibitor of the ABL tyrosine kinase on the growth of BCR-ABL- positive cells // Nat. Med. – 1996. – Vol. 2. – P. 561–566.Druker B.J. Translation of the Philadelphia chromosome into therapy for CML // Blood. – 2008. – Vol. 112. – P. 4808–4815.Druker B.J. Translation of the Philadelphia chromosome into therapy for CML // Blood. – 2008. – Vol. 112. – P. 4808–4815.Druker B.J., Guilhot F., O’Brien S.G. et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia // N. Engl. J. Med. – 2006. – Vol. 7, No. 355 (23). – P. 2408–17.Druker B.J., Guilhot F., O’Brien S.G. et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia // N. Engl. J. Med. – 2006. – Vol. 7, No. 355 (23). – P. 2408–17.Goldman J.M. How I treat chronic myeloid leukemia in the imatinib era // Blood. – 2007. – Vol. 110. – P. 2828–2837.Goldman J.M. How I treat chronic myeloid leukemia in the imatinib era // Blood. – 2007. – Vol. 110. – P. 2828–2837.Golemovic M., Verstovsek S., Giles F. et al. AMN107, a novel aminopyrimidine inhibitor of BCRABL, has in vitro activity against imatinib-resistant chronic myeloid leukemia // Clin. Cancer Res. – 2005. – Vol. 11. – P. 4941–4947Golemovic M., Verstovsek S., Giles F. et al. AMN107, a novel aminopyrimidine inhibitor of BCRABL, has in vitro activity against imatinib-resistant chronic myeloid leukemia // Clin. Cancer Res. – 2005. – Vol. 11. – P. 4941–4947Gordon M.Y. Cellular and molecular mechanisms in chronic myeloid leukemia: biology and treatment // Brit. J. Haematol. – 1996. – Vol. 95. – P. 10–20.Gordon M.Y. Cellular and molecular mechanisms in chronic myeloid leukemia: biology and treatment // Brit. J. Haematol. – 1996. – Vol. 95. – P. 10–20.Hehlmann R., Berger U., Pfirrmann M. et al. Drug treatment is superior to allografting as firstline therapy in chronic myeloid leukemia // Blood. – 2007. – Vol. 109. – P. 4686–4692.Hehlmann R., Berger U., Pfirrmann M. et al. Drug treatment is superior to allografting as firstline therapy in chronic myeloid leukemia // Blood. – 2007. – Vol. 109. – P. 4686–4692.Hehlmann R., Hochhaus A., Baccarani M. on behalf of the European LeukemiaNet: Chronic myeloid leukemia // Lancet. – 2007. – Vol. 370. – P. 342–350.Hehlmann R., Hochhaus A., Baccarani M. on behalf of the European LeukemiaNet: Chronic myeloid leukemia // Lancet. – 2007. – Vol. 370. – P. 342–350.Hochhaus A., Baccarani M., Deininger M. et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib // Leukemia. – 2008. – Vol. 22. – P. 1200– 1206.Hochhaus A., Baccarani M., Deininger M. et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib // Leukemia. – 2008. – Vol. 22. – P. 1200– 1206.Hochhaus A., Kantarjian H.M., Baccarani M. et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy // Blood. – 2007. – Vol. 109. – P. 2303–2309.Hochhaus A., Kantarjian H.M., Baccarani M. et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy // Blood. – 2007. – Vol. 109. – P. 2303–2309.Hughes T., Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukemia // Blood Rev. – 2006. – Vol. 20 (1). – P. 29–41.Hughes T., Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukemia // Blood Rev. – 2006. – Vol. 20 (1). – P. 29–41.Hughes T., Deininger M., Hochhaus A. et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results // Blood. – 2006. – Vol. 108 (1). – P. 28–37.Hughes T., Deininger M., Hochhaus A. et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results // Blood. – 2006. – Vol. 108 (1). – P. 28–37.Hughes T.P., Kaeda J., Branford S. et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia // N. Engl. J. Med. – 2003. – Vol. 349 (15). – P. 1423–1432.Hughes T.P., Kaeda J., Branford S. et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia // N. Engl. J. Med. – 2003. – Vol. 349 (15). – P. 1423–1432.Jabbour E., Cortes J.E., Giles F. et al. Current and emerging treatment options in chronic myeloid leukemia // Cancer. – 2007. – Vol. 109. – P. 2171–2181.Jabbour E., Cortes J.E., Giles F. et al. Current and emerging treatment options in chronic myeloid leukemia // Cancer. – 2007. – Vol. 109. – P. 2171–2181.Jabbour E., Kantarjian H. Chronic myeloid leukemia. Semin Hemat. – 2007. – Vol. 44, Suppl. 1. – S1–S150.Jabbour E., Kantarjian H. Chronic myeloid leukemia. Semin Hemat. – 2007. – Vol. 44, Suppl. 1. – S1–S150.Kantarjian H., Giles F., Wunderle L. et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL // N. Engl. J. Med. – 2006. – Vol. 354. – P. 2542–2551.Kantarjian H., Giles F., Wunderle L. et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL // N. Engl. J. Med. – 2006. – Vol. 354. – P. 2542–2551.Kantarjian H., Pasquini R., Hamerschlak N. et al. Dasatinib or high-dose imatinib for chronicphase chronic myeloid leukemia after failure of first-line imatinib: A randomized phase 2 trial // Blood. – 2008. – Vol. 109. – P. 5143–5150.Kantarjian H., Pasquini R., Hamerschlak N. et al. Dasatinib or high-dose imatinib for chronicphase chronic myeloid leukemia after failure of first-line imatinib: A randomized phase 2 trial // Blood. – 2008. – Vol. 109. – P. 5143–5150.Kantarjian H.M., Cortes J.E., O,Brien S. et al. Imatinib mesylate therapy in newly diagnosed patients with Phyladelphya chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses // Blood. – 2003. – Vol. 101. – P. 97–100.Kantarjian H.M., Cortes J.E., O,Brien S. et al. Imatinib mesylate therapy in newly diagnosed patients with Phyladelphya chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses // Blood. – 2003. – Vol. 101. – P. 97–100.Kantarjian H.M., Talpaz M., O,Brien S. et al. Imatinib mesylate for Phyladelphya chromosome-positive chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results // Clin. Cancer Res. – 2002. – Vol. 8. – P. 2177–2187.Kantarjian H.M., Talpaz M., O,Brien S. et al. Imatinib mesylate for Phyladelphya chromosome-positive chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results // Clin. Cancer Res. – 2002. – Vol. 8. – P. 2177–2187.Kantarjian H.M., O’Brien S., Garcia-Manero G. et al. Very long-term follow-up results of imatinib mesylate therapy in chronic phase chronic myeloid leukemia after failure of interferon alpha therapy // Cancer. – 2012. – Vol. 118 (12). – P. 3116–22.Kantarjian H.M., O’Brien S., Garcia-Manero G. et al. Very long-term follow-up results of imatinib mesylate therapy in chronic phase chronic myeloid leukemia after failure of interferon alpha therapy // Cancer. – 2012. – Vol. 118 (12). – P. 3116–22.Kantarjian H.M., Giles F., Gattermann N. et al. Nilotinib (AMN107), a highly selective BCR- ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome– positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance // Blood. – 2008. – Vol. 110. – P. 3540–3546.Kantarjian H.M., Giles F., Gattermann N. et al. Nilotinib (AMN107), a highly selective BCR- ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome– positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance // Blood. – 2008. – Vol. 110. – P. 3540–3546.Henkes M., van der Kuip H., E Aulitzky W. Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec®, Gleevec™) // Ther. Clin. Risk Manag. – 2008. – Vol. 4 (1). – P. 163–187.Henkes M., van der Kuip H., E Aulitzky W. Therapeutic options for chronic myeloid leukemia: focus on imatinib (Glivec®, Gleevec™) // Ther. Clin. Risk Manag. – 2008. – Vol. 4 (1). – P. 163–187.O,Brien S.G., Guilhot F., Larson R.A. et al. Imatinib compared with interferon and low- dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia // N. Engl. J. Med. – 2003. – Vol. 348. – P. 994–1004.O,Brien S.G., Guilhot F., Larson R.A. et al. Imatinib compared with interferon and low- dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia // N. Engl. J. Med. – 2003. – Vol. 348. – P. 994–1004.Plosker G.J., Robinson D.M. Nilotinib // Drugs. – 2008. – Vol. 68. – P. 449–459.Plosker G.J., Robinson D.M. Nilotinib // Drugs. – 2008. – Vol. 68. – P. 449–459.Puttini M., Coluccia A.M.L., Boschelli F. et al. In vitro and in vivo activity of SKI-606, a novel src-abl inhibitor, against imatinib- resistant BCR-ABL neoplastic cells // Cancer Res. – 2006. – Vol. 66. – P. 11314–11322.Puttini M., Coluccia A.M.L., Boschelli F. et al. In vitro and in vivo activity of SKI-606, a novel src-abl inhibitor, against imatinib- resistant BCR-ABL neoplastic cells // Cancer Res. – 2006. – Vol. 66. – P. 11314–11322.Quintas-Cardama A., Cortes J. Molecular biology of BCR-ABL1–positive chronic myeloid leukemia // Blood. – 2009. – Vol. 113. – P. 1619–1630.Quintas-Cardama A., Cortes J. Molecular biology of BCR-ABL1–positive chronic myeloid leukemia // Blood. – 2009. – Vol. 113. – P. 1619–1630.Shah N, Tran C, Lee FY, et al: Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. – 2004. – 305:399–401.Shah N, Tran C, Lee FY, et al: Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. – 2004. – 305:399–401.Shah N.P., Kantarjian H.M., Kim D.W. et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and - intolerant chronic-phase chronic myeloid leukemia // J. Clin. Oncol. – 2008. – Vol. 26. – P. 3204–3212.Shah N.P., Kantarjian H.M., Kim D.W. et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and - intolerant chronic-phase chronic myeloid leukemia // J. Clin. Oncol. – 2008. – Vol. 26. – P. 3204–3212.Silver R.T., Woolf S.H., Hehlmann R. et al. An evidencebased analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: Developed for the American Society of Hematology // Blood. – 1999. – Vol. 94. – P. 1517– 1536.Silver R.T., Woolf S.H., Hehlmann R. et al. An evidencebased analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: Developed for the American Society of Hematology // Blood. – 1999. – Vol. 94. – P. 1517– 1536.Sokal J.E., Cox E.B., Baccarani M., Tura S., Gomez G.A. et al. // Blood. – 1984. – Vol. 63. – P. 789–799.Sokal J.E., Cox E.B., Baccarani M., Tura S., Gomez G.A. et al. // Blood. – 1984. – Vol. 63. – P. 789–799.Soverini S., Colarossi S., Gnani A. et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphiapositive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia // Clin. Cancer Res. – 2006. – Vol. 12 (24). – P. 7374–7379.Soverini S., Colarossi S., Gnani A. et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphiapositive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia // Clin. Cancer Res. – 2006. – Vol. 12 (24). – P. 7374–7379.Talpaz M., Shah P.S., Kantarjian H. et al. Dasatinib in imatinib-resistant Philadelphia chromosome–positive leukemias // N. Engl. J. Med. – 2006. – Vol. 354. – P. 2531–2541.Talpaz M., Shah P.S., Kantarjian H. et al. Dasatinib in imatinib-resistant Philadelphia chromosome–positive leukemias // N. Engl. J. Med. – 2006. – Vol. 354. – P. 2531–2541.Tokarski J.S., Newitt J.A., Chang C.Y.J. et al. The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib- resistant ABL mutation // Cancer Res. – 2006. – Vol. 66. – P. 5790–5797.Tokarski J.S., Newitt J.A., Chang C.Y.J. et al. The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib- resistant ABL mutation // Cancer Res. – 2006. – Vol. 66. – P. 5790–5797.Wang L., Knight K., Lucas C. et al. The role of serial BCR-ABL transcript monitoring in predicting the emergence of BCR-ABL kinase mutations in imatinib-treated patients with chronic myeloid leukemia // Haematologica. – 2006. – Vol. 91. – P. 235– 239.Wang L., Knight K., Lucas C. et al. The role of serial BCR-ABL transcript monitoring in predicting the emergence of BCR-ABL kinase mutations in imatinib-treated patients with chronic myeloid leukemia // Haematologica. – 2006. – Vol. 91. – P. 235– 239.Weisberg E., Manley P.W., Breitentein W. et al. Characterization of AMN107, a selective inhibitor of native and mutant BCR- ABL // Cancer Cell. – 2005. – Vol. 7. – P. 129–141.Weisberg E., Manley P.W., Breitentein W. et al. Characterization of AMN107, a selective inhibitor of native and mutant BCR- ABL // Cancer Cell. – 2005. – Vol. 7. – P. 129–141.

The authors declare that there are no conflicts of interest present.