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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Oncohematology</journal-id><journal-title-group><journal-title xml:lang="en">Oncohematology</journal-title><trans-title-group xml:lang="ru"><trans-title>Онкогематология</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1818-8346</issn><issn publication-format="electronic">2413-4023</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">349</article-id><article-id pub-id-type="doi">10.17650/1818-8346-2019-14-2-59-69</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>BASIC RESEARCH</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ФУНДАМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ В ПРАКТИЧЕСКОЙ МЕДИЦИНЕ НА СОВРЕМЕННОМ ЭТАПЕ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Ex vivo-model design and evaluation of the sensitivity of blast cells to chemotherapy as a way to personalize the treatment of acute myeloid leukemia</article-title><trans-title-group xml:lang="ru"><trans-title>Разработка ex vivo-модели и оценка химиочувствительности бластных клеток в индивидуализации терапии острых миелоидных лейкозов</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9238-8476</contrib-id><name-alternatives><name xml:lang="en"><surname>Polyakov</surname><given-names>A. S.</given-names></name><name xml:lang="ru"><surname>Поляков</surname><given-names>А. С.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><email>doctorpolyakov@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1213-8472</contrib-id><name-alternatives><name xml:lang="en"><surname>Noskov</surname><given-names>Ya. A.</given-names></name><name xml:lang="ru"><surname>Носков</surname><given-names>Я. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7892-2783</contrib-id><name-alternatives><name xml:lang="en"><surname>Nikitin</surname><given-names>Yu. V.</given-names></name><name xml:lang="ru"><surname>Никитин</surname><given-names>Ю. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0470-1109</contrib-id><name-alternatives><name xml:lang="en"><surname>Tyrenko</surname><given-names>V. V.</given-names></name><name xml:lang="ru"><surname>Тыренко</surname><given-names>В. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2441-9394</contrib-id><name-alternatives><name xml:lang="en"><surname>Kolubaeva</surname><given-names>S. N.</given-names></name><name xml:lang="ru"><surname>Колюбаева</surname><given-names>С. Н.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1964-3690</contrib-id><name-alternatives><name xml:lang="en"><surname>Bogdanov</surname><given-names>A. N.</given-names></name><name xml:lang="ru"><surname>Богданов</surname><given-names>А. Н.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9319-462X</contrib-id><name-alternatives><name xml:lang="en"><surname>Semelev</surname><given-names>V. N.</given-names></name><name xml:lang="ru"><surname>Семелев</surname><given-names>В. Н.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Petrova</surname><given-names>O. R.</given-names></name><name xml:lang="ru"><surname>Петрова</surname><given-names>О. Р.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2990-8621</contrib-id><name-alternatives><name xml:lang="en"><surname>Bondarchuk</surname><given-names>S. V.</given-names></name><name xml:lang="ru"><surname>Бондарчук</surname><given-names>С. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6715-0340</contrib-id><name-alternatives><name xml:lang="en"><surname>Zhogolev</surname><given-names>D. K.</given-names></name><name xml:lang="ru"><surname>Жоголев</surname><given-names>Д. К.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4918-1976</contrib-id><name-alternatives><name xml:lang="en"><surname>Zolotarev</surname><given-names>A. D.</given-names></name><name xml:lang="ru"><surname>Золотарёв</surname><given-names>А. Д.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5884-2057</contrib-id><name-alternatives><name xml:lang="en"><surname>Kovalev</surname><given-names>A. V.</given-names></name><name xml:lang="ru"><surname>Ковалев</surname><given-names>А. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0790-8746</contrib-id><name-alternatives><name xml:lang="en"><surname>Puchkova</surname><given-names>Yu. E.</given-names></name><name xml:lang="ru"><surname>Пучкова</surname><given-names>Ю. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>6 Akademika Lebedeva St., Saint-Petersburg, 194044 Russia</p></bio><bio xml:lang="ru"><p>Россия, 194044 Санкт-Петербург, ул. Академика Лебедева, 6</p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Military Medical Academy named after S.M. Kirov, Ministry of Defense of the Russia</institution></aff><aff><institution xml:lang="ru">ФГБВОУ ВО «Военно-медицинская академия им. С.М. Кирова» Минобороны России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2019-07-26" publication-format="electronic"><day>26</day><month>07</month><year>2019</year></pub-date><volume>14</volume><issue>2</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>59</fpage><lpage>69</lpage><history><date date-type="received" iso-8601-date="2019-07-25"><day>25</day><month>07</month><year>2019</year></date><date date-type="accepted" iso-8601-date="2019-07-25"><day>25</day><month>07</month><year>2019</year></date></history><permissions><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://oncohematology.abvpress.ru/ongm/article/view/349">https://oncohematology.abvpress.ru/ongm/article/view/349</self-uri><abstract xml:lang="en"><p>Despite continuous attempts to improve therapy, the outcomes of acute myeloid leukemia remain almost unchanged over last decades. Drugs made with a more complete understanding of the biology of acute myeloid leukemia do not equal the hopes for better prognosis. The best results are achieved only with high-dose chemotherapy, which is only possible for a limited number of patients. High phenotypic and genotypic heterogeneity of acute myeloid leukemia defines the relevance to develop personalized approaches to therapy, including those based on determination of individual drug sensitivity of blast cells.This article presents the results of developing an ex-vivo model of acute myeloid leukemia, as well as testing of two in vitro sensitivity assessment methods: evaluation of the genotoxicity of drugs in the micronucleus test and vitality and sensitivity to chemotherapy in sorted blast cells. Prospects of individualized therapy of acute myeloid leukemia were determined based on introduction into clinical practice and continuing the research.</p></abstract><trans-abstract xml:lang="ru"><p>Несмотря на постоянные попытки совершенствования терапии, исходы острых миелоидных лейкозов остаются практически неизменными уже на протяжении нескольких десятилетий. Пока не оправдывают надежд на изменение ситуации даже перспективные препараты, создаваемые с учетом более глубокого понимания биологии лейкозов. По-прежнему наилучшие результаты достигаются лишь при высокодозной индукционной химиотерапии, применение которой возможно только у ограниченного числа пациентов. Высокая фенотипическая и генотипическая разнородность миелоидных лейкозов определяет актуальность развития персонифицированных подходов к терапии, в том числе основанных на определении индивидуальной химиочувствительности опухолевых клеток.В статье представлены результаты разработки модели острого миелоидного лейкоза ex vivo, а также апробации 2 методов исследования химиочувствительности in vitro: оценки генотоксичности противоопухолевых препаратов в микроядерном тесте, а также жизнеспособности и химиочувствительности отсортированных бластных клеток. Определены перспективы индивидуализированной терапии миелоидных лейкозов на основании внедрения и дальнейшего совершенствования результатов работы.</p></trans-abstract><kwd-group xml:lang="en"><kwd>acute myeloid leukemia</kwd><kwd>secondary acute myeloid leukemia</kwd><kwd>ex vivo model</kwd><kwd>drug sensitivity testing</kwd><kwd>genotoxicity</kwd><kwd>micronucleus test</kwd><kwd>fluorescence activated cell sorting</kwd><kwd>individualization of drug therapy</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>острый миелоидный лейкоз</kwd><kwd>вторичный острый миелоидный лейкоз</kwd><kwd>модель ex vivo</kwd><kwd>химиочувствительность in vitro</kwd><kwd>генотоксичность</kwd><kwd>микроядерный тест</kwd><kwd>сортировка клеток</kwd><kwd>индивидуализация терапии</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Clinical guidelines for the diagnosis and treatment of adult acute myeloid leukemia. National Hematological Society. Ed. V.G. Savchenko. 2018. 65 p. (In Russ.).</mixed-citation><mixed-citation xml:lang="ru">Клинические рекомендации по диагностике и лечению острых миелоидных лейкозов взрослых. Национальное гематологическое общество. Под ред. В.Г. Савченко. 2018. 65 с.</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><mixed-citation>Granfeldt Østgård L.S., Medeiros B.C., Sengeløv H. et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a National Population-Based Cohort Study. J Clin Oncol 2015;33(31):3641–9. DOI: 10.1200/JCO.2014.60.0890.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Hulegårdh E., Nilsson C., Lazarevic V. et al. Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish acute leukemia registry. Am J Hematol 2015;90(3):208–14. DOI: 10,1002 / ajh.23908.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Valentini C.G., Fianchi L., Voso M.T. et al. Incidence of acute myeloid leukemia after breast cancer. Mediterr J Hematol Infect Dis 2011;3(1):e2011069. DOI: 10.4084/MJHID.2011.069.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Kayser S., Döhner K., Krauter J. et al. The impact of therapyrelated acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood 2011;117(7):2137–45. DOI: 10.1182/blood-2010-08-301713.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Borthakur G., Lin E., Jain N. et al. Survival is poorer in patients with secondary core-binding factor acute myelogenous leukemia compared with de novo corebinding factor leukemia. Cancer 2009;115(14):3217–21. DOI: 10.1002/cncr.24367.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Krug U., Röllig C., Koschmieder A. et al. Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet 2010;376(9757):2000–8. DOI: 10.1016/S0140-6736(10)62105-8.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Walter R.B., Othus M., Borthakur G. et al. Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol 2011;29(33):4417–24. DOI: 10.1200/JCO.2011.35.7525.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Smith S.M., Le Beau M.M., Huo D. et al. Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood 2003;102(1):43–52. DOI: 10.1182/blood-2002-11-3343.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Larson R.A. Etiology and management of therapy-related myeloid leukemia. Hematology Am Soc Hematol Educ Program 2007;(1):453–9. DOI: 10.1182/asheducation-2007.1.453.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Christiansen D.H., Andersen M.K., Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 2001;19(5):1405–13. DOI: 10.1200/JCO.2001.19.5.1405.</mixed-citation></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">Löwenberg B., Ossenkoppele G.J., van Putten W. et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 2009;361(13):1235–48. DOI: 10,1056/NEJMoa0901409.</mixed-citation><mixed-citation xml:lang="ru">Löwenberg B., Ossenkoppele G.J., van Putten W. et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med</mixed-citation></citation-alternatives></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">Boddu P., Kantarjian H.M., Garcia-Manero G. et al. Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis. Blood Adv 2017;1(17):1312–23. DOI: 10.1182/bloodadvances.2017008227.</mixed-citation><mixed-citation xml:lang="ru">;361(13):1235–48. DOI: 10,1056/NEJMoa0901409.</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">Lancet J.E., Uy G.L., Cortes J.E. et al. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol 2016;34(15):7000. DOI: 10.1200/JCO.2016.34.15_suppl.7000.</mixed-citation><mixed-citation xml:lang="ru">Boddu P., Kantarjian H.M., Garcia-Manero G. et al. Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis. Blood Adv 2017;1(17):1312–23. DOI: 10.1182/bloodadvances.2017008227.</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">Michelis F.V., Atenafu E.G., Gupta V. et al. Comparable outcomes post allogeneic hematopoietic cell transplant for patients with de novo or secondary acute myeloid leukemia in first remission. Bone Marrow Transplant 2015;50(7):907–13. DOI: 10.1038/bmt.2015.59.</mixed-citation><mixed-citation xml:lang="ru">Lancet J.E., Uy G.L., Cortes J.E. et al. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol 2016;34(15):7000. DOI: 10.1200/JCO.2016.34.15_suppl.7000.</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">Tang F.F., Huang X.J., Zhang X.H. et al. Allogeneic hematopoietic cell transplantation for adult patients with treatmentrelated acute myeloid leukemia during first remission: comparable to de novo acute myeloid leukemia. Leuk Res 2016;47:8–15. DOI: 10.1016/j.leukres.2016.05.005.</mixed-citation><mixed-citation xml:lang="ru">Michelis F.V., Atenafu E.G., Gupta V. et al. Comparable outcomes post allogeneic hematopoietic cell transplant for patients with de novo or secondary acute myeloid leukemia in first remission. Bone Marrow Transplant 2015;50(7):907–13. DOI: 10.1038/bmt.2015.59.</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><citation-alternatives><mixed-citation xml:lang="en">Ravandi F., Issa J.P., Garcia-Manero G. et al. Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities. Cancer 2009;115(24):5746–51. DOI: 10.1002/cncr.24661.</mixed-citation><mixed-citation xml:lang="ru">Tang F.F., Huang X.J., Zhang X.H. et al. Allogeneic hematopoietic cell transplantation for adult patients with treatmentrelated acute myeloid leukemia during first remission: comparable to de novo acute myeloid leukemia. Leuk Res 2016;47:8–15. DOI: 10.1016/j.leukres.2016.05.005.</mixed-citation></citation-alternatives></ref><ref id="B18"><label>18.</label><citation-alternatives><mixed-citation xml:lang="en">Boddu P.C., Kantarjian H.M., Ravandi F. et al. Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach. Cancer 2017;123(16):3050–60. DOI: 10.1002/cncr.30704.</mixed-citation><mixed-citation xml:lang="ru">Ravandi F., Issa J.P., Garcia-Manero G. et al. Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities. Cancer 2009;115(24):5746–51. DOI: 10.1002/cncr.24661.</mixed-citation></citation-alternatives></ref><ref id="B19"><label>19.</label><citation-alternatives><mixed-citation xml:lang="en">Maurillo L., Buccisano F., Spagnoli A. et al. Comparative analysis of azacitidine and intensive chemotherapy as front-line treatment of elderly patients with acute myeloid leukemia. Ann Hematol 2018;97:1767–74. DOI: 10,1007/s00277-018-3374-х.</mixed-citation><mixed-citation xml:lang="ru">Boddu P.C., Kantarjian H.M., Ravandi F. et al. Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach. Cancer 2017;123(16):3050–60. DOI: 10.1002/cncr.30704.</mixed-citation></citation-alternatives></ref><ref id="B20"><label>20.</label><citation-alternatives><mixed-citation xml:lang="en">Lancet J.E., Uy G.L., Cortes J.E. et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol 2018;36(26):2684–92. DOI: 10,1200 /JCO.2017.77.6112.</mixed-citation><mixed-citation xml:lang="ru">Maurillo L., Buccisano F., Spagnoli A. et al. Comparative analysis of azacitidine and intensive chemotherapy as front-line treatment of elderly patients with acute myeloid leukemia. Ann Hematol 2018;97:1767–74. DOI: 10,1007/s00277-018-3374-х.</mixed-citation></citation-alternatives></ref><ref id="B21"><label>21.</label><citation-alternatives><mixed-citation xml:lang="en">Petersdorf S.H., Kopecky K.J., Slovak M. et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood 2013;121(24):4854–60. DOI: 10.1182/blood-2013-01-466706.</mixed-citation><mixed-citation xml:lang="ru">Lancet J.E., Uy G.L., Cortes J.E. et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol 2018;36(26):2684–92. DOI: 10,1200 /JCO.2017.77.6112.</mixed-citation></citation-alternatives></ref><ref id="B22"><label>22.</label><citation-alternatives><mixed-citation xml:lang="en">Castaigne S., Pautas C., Terré C. et al. Final analysis of the ALFA 0701 study. Blood 2014;124(21):376.</mixed-citation><mixed-citation xml:lang="ru">Petersdorf S.H., Kopecky K.J., Slovak M. et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood 2013;121(24):4854–60. DOI: 10.1182/blood-2013-01-466706.</mixed-citation></citation-alternatives></ref><ref id="B23"><label>23.</label><citation-alternatives><mixed-citation xml:lang="en">Burnett A.K., Russell N.H., Hills R.K. et al. Addition of Gemtuzumab Ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol 2012;30(32):3924–31. DOI: 10,1200/JCO.2012.42.2964.</mixed-citation><mixed-citation xml:lang="ru">Castaigne S., Pautas C., Terré C. et al. Final analysis of the ALFA 0701 study. Blood 2014;124(21):376.</mixed-citation></citation-alternatives></ref><ref id="B24"><label>24.</label><citation-alternatives><mixed-citation xml:lang="en">Stone R.M., Mazzola E., Neuberg D. et al. Phase III open-label randomized study of Cytarabine in combination with Amonafide L-malate or Daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol 2015;33(11):1252–7. DOI: 10,1200/JCO.2014.57.0952.</mixed-citation><mixed-citation xml:lang="ru">Burnett A.K., Russell N.H., Hills R.K. et al. Addition of Gemtuzumab Ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol 2012;30(32):3924–31. DOI: 10,1200/JCO.2012.42.2964.</mixed-citation></citation-alternatives></ref><ref id="B25"><label>25.</label><citation-alternatives><mixed-citation xml:lang="en">Pratz K.W., Rudek M.A., Gojo I. et al. A phase I study of Topotecan, carboplatin and the PARP inhibitor Veliparib in acute Leukemias, aggressive myeloproliferative neoplasms, and chronic Myelomonocytic leukemia. Clin Cancer Res 2017;23(4):899–907. DOI: 10.1158/1078-0432.CCR-16-1274.</mixed-citation><mixed-citation xml:lang="ru">Stone R.M., Mazzola E., Neuberg D. et al. Phase III open-label randomized study of Cytarabine in combination with Amonafide L-malate or Daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol 2015;33(11):1252–7. DOI: 10,1200/JCO.2014.57.0952.</mixed-citation></citation-alternatives></ref><ref id="B26"><label>26.</label><citation-alternatives><mixed-citation xml:lang="en">Zeidner J.F., Foster M.C., Blackford A.L. et al. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7 + 3) in newly diagnosed acute myeloid leukemia. Haematologica 2015;100(9):1172–9. DOI: 10,3324/Haematol.2015.125849.</mixed-citation><mixed-citation xml:lang="ru">Pratz K.W., Rudek M.A., Gojo I. et al. A phase I study of Topotecan, carboplatin and the PARP inhibitor Veliparib in acute Leukemias, aggressive myeloproliferative neoplasms, and chronic Myelomonocytic leukemia. Clin Cancer Res 2017;23(4):899–907. DOI: 10.1158/1078-0432.CCR-16-1274.</mixed-citation></citation-alternatives></ref><ref id="B27"><label>27.</label><citation-alternatives><mixed-citation xml:lang="en">Willemze R., Suciu S., Meloni G. et al. High-dose Cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol 2014;32(3):219–28. DOI: 10,1200/JCO.2013.51.8571.</mixed-citation><mixed-citation xml:lang="ru">Zeidner J.F., Foster M.C., Blackford A.L. et al. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7 + 3) in newly diagnosed acute myeloid leukemia. Haematologica 2015;100(9):1172–9. DOI: 10,3324/Haematol.2015.125849.</mixed-citation></citation-alternatives></ref><ref id="B28"><label>28.</label><citation-alternatives><mixed-citation xml:lang="en">Bashey A., Liu L., Ihasz A. et al. Nonanthracycline based remission induction therapy for newly diagnosed patients with acute myeloid leukemia aged 60 or older. Leuk Res 2006;30(4):503–6. DOI: 10,1016/j.leukres.2005.09.002.</mixed-citation><mixed-citation xml:lang="ru">Willemze R., Suciu S., Meloni G. et al. High-dose Cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol 2014;32(3):219–28. DOI: 10,1200/JCO.2013.51.8571.</mixed-citation></citation-alternatives></ref><ref id="B29"><label>29.</label><citation-alternatives><mixed-citation xml:lang="en">Ferrara F., Palmieri S., Izzo T. et al. Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome. Hematol Oncol 2010;28(4):202–8. DOI: 10,1002/hon.943.</mixed-citation><mixed-citation xml:lang="ru">Bashey A., Liu L., Ihasz A. et al. Nonanthracycline based remission induction therapy for newly diagnosed patients with acute myeloid leukemia aged 60 or older. Leuk Res 2006;30(4):503–6. DOI: 10,1016/j.leukres.2005.09.002.</mixed-citation></citation-alternatives></ref><ref id="B30"><label>30.</label><citation-alternatives><mixed-citation xml:lang="en">Becker P.S., Medeiros B.C., Stein A.S. et al. G-CSF priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm. Am J Hematol 2015;90(4):295–300. DOI: 10,1002/ajh.23927.</mixed-citation><mixed-citation xml:lang="ru">Ferrara F., Palmieri S., Izzo T. et al. Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome. Hematol Oncol 2010;28(4):202–8. DOI: 10,1002/hon.943.</mixed-citation></citation-alternatives></ref><ref id="B31"><label>31.</label><citation-alternatives><mixed-citation xml:lang="en">Jeong E., Moon S.U., Song M. et al. Transcriptome modeling and phenotypic assays for cancer precision medicine. Arch Pharm Res 2017;40(8):906–14. DOI: 10,1007/s12272-017-0940-z.</mixed-citation><mixed-citation xml:lang="ru">Becker P.S., Medeiros B.C., Stein A.S. et al. G-CSF priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm. Am J Hematol 2015;90(4):295–300. DOI: 10,1002/ajh.23927.</mixed-citation></citation-alternatives></ref><ref id="B32"><label>32.</label><citation-alternatives><mixed-citation xml:lang="en">Muraro M.G., Muenst S., Mele V. et al. Ex-vivo assessment of drug response on breast cancer primary tissue with preserved microenvironments. Oncoimmunology 2017;6(7):e1331798. DOI: 10,1080/2162402X.2017.1331798.</mixed-citation><mixed-citation xml:lang="ru">Jeong E., Moon S.U., Song M. et al. Transcriptome modeling and phenotypic assays for cancer precision medicine. Arch Pharm Res 2017;40(8):906–14. DOI: 10,1007/s12272-017-0940-z.</mixed-citation></citation-alternatives></ref><ref id="B33"><label>33.</label><citation-alternatives><mixed-citation xml:lang="en">Meijer T.G., Naipal K.A., Jager A. et al. Ex vivo tumor culture systems for functional drug testing and therapy response prediction. Future Sci OA 2017;3(2):FSO190. DOI: 10.4155/fsoa-2017-0003.</mixed-citation><mixed-citation xml:lang="ru">Muraro M.G., Muenst S., Mele V. et al. Ex-vivo assessment of drug response on breast cancer primary tissue with preserved microenvironments. Oncoimmunology 2017;6(7):e1331798. DOI: 10,1080/2162402X.2017.1331798.</mixed-citation></citation-alternatives></ref><ref id="B34"><label>34.</label><citation-alternatives><mixed-citation xml:lang="en">Yadav B., Pemovska T., Szwajda A. et al. Quantitative scoring of differential drug sensitivity for individually optimized anticancer therapies. Sci Rep 2014;4:5193. DOI: 10.1038/srep05193.</mixed-citation><mixed-citation xml:lang="ru">Meijer T.G., Naipal K.A., Jager A. et al. Ex vivo tumor culture systems for functional drug testing and therapy response prediction. Future Sci OA 2017;3(2):FSO190. DOI: 10.4155/fsoa-2017-0003.</mixed-citation></citation-alternatives></ref><ref id="B35"><label>35.</label><citation-alternatives><mixed-citation xml:lang="en">Brigulová K., Cervinka M., Tošner J. et al. Chemoresistance testing of human ovarian cancer cells and its in vitro model. Toxicol In Vitro 2010;24(8):2108–15. DOI: 10,1016/j.tiv.2010.08.010.</mixed-citation><mixed-citation xml:lang="ru">Yadav B., Pemovska T., Szwajda A. et al. Quantitative scoring of differential drug sensitivity for individually optimized anticancer therapies. Sci Rep 2014;4:5193. DOI: 10.1038/srep05193.</mixed-citation></citation-alternatives></ref><ref id="B36"><label>36.</label><citation-alternatives><mixed-citation xml:lang="en">Ehemann V., Kern M.A., Breinig M. et al. Establishment, characterization and drug sensitivity testing in primary cultures of human thymoma and thymic carcinoma. Int J Cancer 2008;122(12): 2719–25. DOI: 10.1002/ijc.23335.</mixed-citation><mixed-citation xml:lang="ru">Brigulová K., Cervinka M., Tošner J. et al. Chemoresistance testing of human ovarian cancer cells and its in vitro model. Toxicol In Vitro 2010;24(8):2108–15. DOI: 10,1016/j.tiv.2010.08.010.</mixed-citation></citation-alternatives></ref><ref id="B37"><label>37.</label><citation-alternatives><mixed-citation xml:lang="en">Ferris J.S., Rice L.W. The role of in vitro directed chemptherapy in epithelial ovarian cancer. Revoews Obsterics Gynecology 2010;3(2):49–54.</mixed-citation><mixed-citation xml:lang="ru">Ehemann V., Kern M.A., Breinig M. et al. Establishment, characterization and drug sensitivity testing in primary cultures of human thymoma and thymic carcinoma. Int J Cancer 2008;122(12): 2719–25. DOI: 10.1002/ijc.23335.</mixed-citation></citation-alternatives></ref><ref id="B38"><label>38.</label><citation-alternatives><mixed-citation xml:lang="en">Pemovska T., Kontro M., Yadav B. et al. Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discov 2013;3(12):1416–29. DOI: 10,1158/2159-8290.CD-13-0350.</mixed-citation><mixed-citation xml:lang="ru">Ferris J.S., Rice L.W. The role of in vitro directed chemptherapy in epithelial ovarian cancer. Revoews Obsterics Gynecology 2010;3(2):49–54.</mixed-citation></citation-alternatives></ref><ref id="B39"><label>39.</label><citation-alternatives><mixed-citation xml:lang="en">Bosanquet A.G., Bell P.B. Ex vivo therapeutic index by drug sensitivity assay using fresh human normal and tumor cells. J Exp Ther Oncol 2004;4(2):145–54.</mixed-citation><mixed-citation xml:lang="ru">Pemovska T., Kontro M., Yadav B. et al. Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discov 2013;3(12):1416–29. DOI: 10,1158/2159-8290.CD-13-0350.</mixed-citation></citation-alternatives></ref><ref id="B40"><label>40.</label><citation-alternatives><mixed-citation xml:lang="en">Kaspers G.J., Veerman A.J., Pieters R. et al. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood 1997;90(7):2723–9.</mixed-citation><mixed-citation xml:lang="ru">Bosanquet A.G., Bell P.B. Ex vivo therapeutic index by drug sensitivity assay using fresh human normal and tumor cells. J Exp Ther Oncol 2004;4(2):145–54.</mixed-citation></citation-alternatives></ref><ref id="B41"><label>41.</label><citation-alternatives><mixed-citation xml:lang="en">Dogan A.L., Kars A., Canpinar H. Prediction of clinical response to chemotherapy by in vitro chemosensitivity assay in acute leukemia. Turk J Cancer 2004;34(2):75–80.</mixed-citation><mixed-citation xml:lang="ru">Kaspers G.J., Veerman A.J., Pieters R. et al. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood 1997;90(7):2723–9.</mixed-citation></citation-alternatives></ref><ref id="B42"><label>42.</label><citation-alternatives><mixed-citation xml:lang="en">Kurtz S.E., Eide C.A., Kaempf A. et al. Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies. Proc Natl Acad Sci USA 2017;114(36):7554–63. DOI: 10.1073/pnas.1703094114.</mixed-citation><mixed-citation xml:lang="ru">Dogan A.L., Kars A., Canpinar H. Prediction of clinical response to chemotherapy by in vitro chemosensitivity assay in acute leukemia. Turk J Cancer 2004;34(2):75–80.</mixed-citation></citation-alternatives></ref><ref id="B43"><label>43.</label><citation-alternatives><mixed-citation xml:lang="en">Snijder B., Vladimer G.I., Krall N. et al. Image-based ex vivo drug screening for patients with aggressive haematological malignancies: interim results from a singlearm, open-label, pilot study. Lancet Haematol 2017;4(12):595–606. DOI: 10.1016/S2352-3026(17)30208-30209.</mixed-citation><mixed-citation xml:lang="ru">Kurtz S.E., Eide C.A., Kaempf A. et al. Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies. Proc Natl Acad Sci USA 2017;114(36):7554–63. DOI: 10.1073/pnas.1703094114.</mixed-citation></citation-alternatives></ref><ref id="B44"><label>44.</label><citation-alternatives><mixed-citation xml:lang="en">Swords R.T., Azzam D., Al-Ali H. et al. Ex vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: a pilot study. Leukemia Res 2017;64:34–41. DOI: 10.1016/j.leukres.2017.11.008.</mixed-citation><mixed-citation xml:lang="ru">Snijder B., Vladimer G.I., Krall N. et al. Image-based ex vivo drug screening for patients with aggressive haematological malignancies: interim results from a singlearm, open-label, pilot study. Lancet Haematol 2017;4(12):595–606. DOI: 10.1016/S2352-3026(17)30208-30209.</mixed-citation></citation-alternatives></ref><ref id="B45"><label>45.</label><citation-alternatives><mixed-citation xml:lang="en">Le Tourneau C., Kamal M., Tsimberidou A.M. et al. Treatment algorithms based on tumor molecular profiling: the essence of precision medicine trials. J Natl Cancer Inst 2016;108(4). DOI: 10.1093/JNCI/djv362.</mixed-citation><mixed-citation xml:lang="ru">Swords R.T., Azzam D., Al-Ali H. et al. Ex vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: a pilot study. Leukemia Res 2017;64:34–41. DOI: 10.1016/j.leukres.2017.11.008.</mixed-citation></citation-alternatives></ref><ref id="B46"><label>46.</label><citation-alternatives><mixed-citation xml:lang="en">Megias-Vericat J., Martines-Cuadron D., Lopez J. et al. Differences in ex vivo chemosensitivity to anthracyclines in first line acute myeloid leukemia. Mediterr J Hematol Infect Dis 2019;11:e2019016. DOI: 10.4084/mjhid.2019.016.</mixed-citation><mixed-citation xml:lang="ru">Le Tourneau C., Kamal M., Tsimberidou A.M. et al. Treatment algorithms based on tumor molecular profiling: the essence of precision medicine trials. J Natl Cancer Inst 2016;108(4). DOI: 10.1093/JNCI/djv362.</mixed-citation></citation-alternatives></ref><ref id="B47"><label>47.</label><citation-alternatives><mixed-citation xml:lang="en">Hernandes P., Gorrochategui J., Primo D. et al. Drug discovery testing compounds in patient samples by automated f low cytometry. SLAS Technology 2017;22(3):325–37. DOI: 10.1177/2472630317700346.</mixed-citation><mixed-citation xml:lang="ru">Megias-Vericat J., Martines-Cuadron D., Lopez J. et al. Differences in ex vivo chemosensitivity to anthracyclines in first line acute myeloid leukemia. Mediterr J Hematol Infect Dis 2019;11:e2019016. DOI: 10.4084/mjhid.2019.016.</mixed-citation></citation-alternatives></ref><ref id="B48"><label>48.</label><mixed-citation>Hernandes P., Gorrochategui J., Primo D. et al. Drug discovery testing compounds in patient samples by automated f low cytometry. SLAS Technology 2017;22(3):325–37. DOI: 10.1177/2472630317700346.</mixed-citation></ref></ref-list></back></article>
