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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">Pediatric Hematology/Oncology and Immunopathology</journal-id><journal-title-group><journal-title xml:lang="en">Pediatric Hematology/Oncology and Immunopathology</journal-title><trans-title-group xml:lang="ru"><trans-title>Вопросы гематологии/онкологии и иммунопатологии в педиатрии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1726-1708</issn><issn publication-format="electronic">2414-9314</issn><publisher><publisher-name xml:lang="en">Fund Doctors, Innovations, Science for Children</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">280</article-id><article-id pub-id-type="doi">10.24287/1726-1708-2019-18-4-19-28</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Therapy intensification in high-risk neuroblastoma patients with poor response to standard induction: experience of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology</article-title><trans-title-group xml:lang="ru"><trans-title>Интенсификация индукционной терапии у пациентов с нейробластомой группы высокого риска с плохим ответом на индукционную терапию: опыт НМИЦ ДГОИ им. Дмитрия Рогачева</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3767-4477</contrib-id><name-alternatives><name xml:lang="en"><surname>Shamanskaya</surname><given-names>T. V.</given-names></name><name xml:lang="ru"><surname>Шаманская</surname><given-names>Т. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><bold>Correspondence:</bold><bold> </bold>Tatyana V. Shamanskaya, MD, PhD,Scientific Secretary,Institute ofOncology, Radiology and Nuclear Medicine, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology Ministry of Healthcare ofRussian Federation.</p><p><italic>Address: Russia 117997, Moscow,Samory Mashela st., 1</italic></p></bio><bio xml:lang="ru"><p/><p><bold>Контактная информация:</bold><bold> </bold>Шаманская Татьяна Викторовна, канд. мед. наук, ученый секретарь Института онкологии, радиологии и ядерной медицины НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздрава России.</p><italic>Адрес: 117997, Москва, ул. СаморыМашела, д. 1</italic></bio><email>shamanskaya.tatyana@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3704-8783</contrib-id><name-alternatives><name xml:lang="en"><surname>Kachanov</surname><given-names>D. Y.</given-names></name><name xml:lang="ru"><surname>Качанов</surname><given-names>Д. Ю.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p><italic>Москва</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Dumacheva</surname><given-names>A. V.</given-names></name><name xml:lang="ru"><surname>Думачева</surname><given-names>А. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>Moscow</italic></p></bio><bio xml:lang="ru"><p><italic>Москва</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4042-0125</contrib-id><name-alternatives><name xml:lang="en"><surname>Teleshova</surname><given-names>M. V.</given-names></name><name xml:lang="ru"><surname>Телешова</surname><given-names>М. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>Moscow</italic></p></bio><bio xml:lang="ru"><p><italic>Москва</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7439-4431</contrib-id><name-alternatives><name xml:lang="en"><surname>Shevtcov</surname><given-names>D. V.</given-names></name><name xml:lang="ru"><surname>Шевцов</surname><given-names>Д. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>Moscow</italic></p></bio><bio xml:lang="ru"><p><italic>Москва</italic></p></bio><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Sergeeva</surname><given-names>T. V.</given-names></name><name xml:lang="ru"><surname>Сергеева</surname><given-names>Т. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>Moscow</italic></p></bio><bio xml:lang="ru"><p><italic>Москва</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5489-1879</contrib-id><name-alternatives><name xml:lang="en"><surname>Syleimanova</surname><given-names>A. M.</given-names></name><name xml:lang="ru"><surname>Сулейманова</surname><given-names>А. М.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>Moscow</italic></p></bio><bio xml:lang="ru"><p><italic>Москва</italic></p></bio><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9654-084X</contrib-id><name-alternatives><name xml:lang="en"><surname>Moiseenko</surname><given-names>R. A.</given-names></name><name xml:lang="ru"><surname>Моисеенко</surname><given-names>Р. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>Moscow</italic></p></bio><bio xml:lang="ru"><p><italic>Москва</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6158-2222</contrib-id><name-alternatives><name xml:lang="en"><surname>Likar</surname><given-names>Y. N.</given-names></name><name xml:lang="ru"><surname>Ликарь</surname><given-names>Ю. Н.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>Moscow</italic></p></bio><bio xml:lang="ru"><p><italic>Москва</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7427-4560</contrib-id><name-alternatives><name xml:lang="en"><surname>Kailash</surname><given-names>.</given-names></name><name xml:lang="ru"><surname>Кайлаш</surname><given-names>.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>Moscow</italic></p></bio><bio xml:lang="ru"><p><italic>Москва</italic></p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6131-1783</contrib-id><name-alternatives><name xml:lang="en"><surname>Varfolomeeva</surname><given-names>S. R.</given-names></name><name xml:lang="ru"><surname>Варфоломеева</surname><given-names>С. Р.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><italic>Moscow</italic></p></bio><xref ref-type="aff" rid="aff3"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology Ministry of Healthcare of Russian Federation</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">N.N. Blokhin National Medical Research Center of Oncology оf the Ministry of Health of the Russian Federation</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">N.N. Blokhin National Medical Research Center of Oncology оf the Ministry of Health of the Russian Federation</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2019-12-31" publication-format="electronic"><day>31</day><month>12</month><year>2019</year></pub-date><volume>18</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>19</fpage><lpage>28</lpage><history><date date-type="received" iso-8601-date="2019-12-29"><day>29</day><month>12</month><year>2019</year></date><date date-type="accepted" iso-8601-date="2019-12-29"><day>29</day><month>12</month><year>2019</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2019, «D. Rogachev NMRCPHOI»</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2019, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="en">«D. Rogachev NMRCPHOI»</copyright-holder><copyright-holder xml:lang="ru">ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://hemoncim.com/jour/article/view/280">https://hemoncim.com/jour/article/view/280</self-uri><abstract xml:lang="en"><p>High-risk neuroblastoma (NB) is characterized by unsatisfactory treatment results and low probability of long-term survival despite the multimodal therapeutic approach (chemotherapy, surgical treatment, radiation therapy, autologous hematopoietic stem cell transplantation, etc.). One of the prognostic factors in this cohort of patients is the response to induction therapy. The article presents the experience of the intensification of induction therapy in 12 patients with high-risk NB with a poor response (mixed response, stable disease) to standard induction therapy who received treatment at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, assessing its impact on the prognosis of the disease. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Patients received an additional two courses of chemotherapy with the inclusion of a type I topoisomerase inhibitor topotecan (TCE – topotecan, cyclophosphamide, etoposide). This regimen of intensification of therapy has demonstrated its feasibility. The main grade 3–4 toxicity was hematologic. An improvement in response was achieved in 5/12 (41.6%) patients. However, long-term results of therapy remained unsatisfactory. The 3-year EFS was 16.7% (95% CI 0.0–37.8), the 3-year OS was 50.0% (95% CI 21.7–78.3). Thus, the intensification of therapy in patients with high-risk NB with a poor response to standard induction therapy did not improve treatment outcomes.</p></abstract><trans-abstract xml:lang="ru"><p>Нейробластома (НБ) группы высокого риска, несмотря на мультимодальный подход к терапии (химиотерапия, хирургическое лечение, лучевая терапия, аутологичная трансплантация гемопоэтических стволовых клеток и др.), характеризуется неудовлетворительными результатами лечения и низкими показателями долгосрочной выживаемости. Один из прогностических факторов в данной когорте пациентов – ответ на индукционную терапию. В статье представлен опыт интенсификации индукционной терапии у 12 пациентов с НБ группы высокого риска с плохим ответом на индукционную терапию (смешанный ответ и стабилизация), получавших лечение в НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздрава России, а также оценки ее влияния на прогноз заболевания. Данное исследование поддержано Независимым этическим комитетом и утверждено решением Ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева Минздрава России. Пациенты получали дополнительно два курса химиотерапии с включением ингибитора топоизомеразы I типа – топотекана. Данный режим интенсификации терапии продемонстрировал, что его применение выполнимо; ни в одном случае не было отмечено летального исхода, обусловленного токсичностью терапии. Основной профиль токсичности 3–4 степени – гематологическая. Улучшение ответа было достигнуто у 5 (41,6%) больных. Однако отдаленные результаты терапии оставались неудовлетворительными: 3-летняя бессобытийная выживаемость составила 16,7% (95% ДИ 0,0–37,8); 3-летняя общая выживаемость – 50,0% (95% ДИ 21,7–78,3). Таким образом, интенсификация терапии у пациентов с НБ группы высокого риска и плохим ответом на стандартную индукционную терапию не улучшила результаты лечения.</p></trans-abstract><kwd-group xml:lang="en"><kwd>neuroblastoma</kwd><kwd>children</kwd><kwd>high-risk group</kwd><kwd>induction therapy</kwd><kwd>topotecan</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>нейробластома</kwd><kwd>дети</kwd><kwd>группа высокого риска</kwd><kwd>индукционная терапия</kwd><kwd>топотекан</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Goodman M.T., Gurney J.G., Smith M.A., Olsham A.F. Sympathetic nervous system tumors. In: Ries LAG, Smith MA, Gurney JG, et al, eds. Сancer incidence and survival among children and adolescents: United States SEER Program 1975–1995. 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