<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" 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" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">nodgo</journal-id><journal-title-group><journal-title xml:lang="ru">Российский журнал детской гематологии и онкологии (РЖДГиО)</journal-title><trans-title-group xml:lang="en"><trans-title>Russian Journal of Pediatric Hematology and Oncology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2311-1267</issn><issn pub-type="epub">2413-5496</issn><publisher><publisher-name>LTD “Graphica”</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21682/2311-1267-2020-7-3-13-21</article-id><article-id custom-type="elpub" pub-id-type="custom">nodgo-620</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL STUDIES</subject></subj-group></article-categories><title-group><article-title>Особенности клинического течения и биологических характеристик нейробластомы у подростков и молодых взрослых. Описание серии клинических случаев и обзор литературы</article-title><trans-title-group xml:lang="en"><trans-title>Clinical and biological characteristics of neuroblastoma in adolescents and young adults. Case study and literature review</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3818-6213</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Казанцев</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kazantsev</surname><given-names>I. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Илья Викторович Казанцев, врач-детский онколог отделения трансплантации костного мозга для детей № 2 НИИ ДОГиТ им. Р.М. Горбачевой, ассистент кафедры гематологии, трансфузиологии и трансплантологии ПСПбГМУ им. акад. И.П. Павлова</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Assistant for Hematology, Transfusiology and Transpantation Chair ofI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">Ilya_Kazantsev@inbox.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2905-8209</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Геворгян</surname><given-names>А. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Gevorgyan</surname><given-names>A. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандидат медицинских наук, заведующая отделением трансплантации костного мозга для детей № 2 НИИ ДОГиТ им. Р.М. Горбачевой, ассистент кафедры гематологии, трансфузиологии и трансплантологии ПСПбГМУ им. акад. И.П. Павлова</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Cand. of Sci. (Med.), Head of the 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Assistant for Hematology, Transfusiology and Transpantation Chair atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">asmikgevorgian@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5979-9182</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Юхта</surname><given-names>Т. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Yukhta</surname><given-names>T. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Врач-детский онколог отделения трансплантации костного мозга для детей № 2 НИИ ДОГиТ им. Р.М. Горбачевой</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p><p>SPIN-код: 2552-7003</p></bio><bio xml:lang="en"><p>Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation</p><p>12 Rentgena St., Saint Petersburg, 197022</p><p>SPIN-code: 2552-7003</p></bio><email xlink:type="simple">tania.juh@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2296-0358</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Толкунова</surname><given-names>П. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Tolkunova</surname><given-names>P. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Врач-детский онколог отделения трансплантации костного мозга для детей № 2 НИИ ДОГиТ им. Р.М. Горбачевой</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">tolkunova_polina@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4072-601X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Козлов</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kozlov</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандидат медицинских наук, старший научный сотрудник ПСПбГМУ им. акад. И.П. Павлова, доцент кафедры гематологии, трансфузиологии и трансплантологии ПСПбГМУ им. акад. И.П. Павлова</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Cand. of Sci. (Med.), Senior Research Associate, Associate Professor for Hematology, Transfusiology and Transpantation Chair atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">kozlovandrew1983@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7435-4616</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Звягинцева</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Zvyagintseva</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандидат медицинских наук, врач-детский онколог отделения трансплантации костного мозга для детей № 2 НИИ ДОГиТ им. Р.М. Горбачевой</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Cand. of Sci. (Med.), Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">zvyagintseva.doc@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8227-8257</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Голенкова</surname><given-names>М. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Golenkova</surname><given-names>M. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Врач-детский онколог отделения трансплантации костного мозга для детей № 2 НИИ ДОГиТ им. Р.М. Горбачевой</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">msgolenkova24@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1286-6069</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Богданова</surname><given-names>О. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Bogdanova</surname><given-names>O. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Врач-детский онколог отделения трансплантации костного мозга для детей № 2 НИИ ДОГиТ им. Р.М. Горбачевой</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">olbogdanova03@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7173-7673</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Швецов</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Shvetsov</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Заведующий отделением хирургии НИИ ДОГиТ им. Р.М. Горбачевой</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Head of Surgery Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">9052557239@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9605-485X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Морозова</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Morozova</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандидат медицинских наук, доцент кафедры гематологии, трансфузиологии и трансплантологии ПСПбГМУ им. акад. И.П. Павлова</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Cand. of Sci. (Med.), Associate Professor for Hematology, Transfusiology and Transpantation Chair atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">dr_morozova@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8589-4618</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Николаев</surname><given-names>И. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Nikolaev</surname><given-names>I. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Врач-рентгенолог отделения рентгеновской компьютерной томографии № 1 НИИ ДОГиТ им. Р.М. Горбачевой</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Radiologist of the Department of X-ray Computed Tomography No. 1 atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">ilya511@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4536-1152</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сафонова</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Safonova</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кандидат медицинских наук, врач-детский онколог отделения трансплантации костного мозга для детей № 2 НИИ ДОГиТ им. Р.М. Горбачевой</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Cand. of Sci. (Med.), Pediatric Oncologist 2nd Pediatric Transplant Department at Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">safonovasa@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0445-8452</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пунанов</surname><given-names>Ю. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Punanov</surname><given-names>Yu. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, профессор кафедры гематологии, трансфузиологии и трансплантологии ПСПбГМУ им. акад. И.П. Павлова</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Dr. of Sci. (Med.), Professor for Hematology, Transfusiology and Transpantation Chair atI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">punanovyu55@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2594-7703</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Зубаровская</surname><given-names>Л. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Zubarovskaya</surname><given-names>L. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, профессор кафедры гематологии, трансфузиологии и трансплантологии ПСПбГМУ им. акад. И.П. Павлова</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Dr. of Sci. (Med.), Professor for Hematology, Transfusiology and Transpantation Chair ofI.P.PavlovSaint-PetersburgFirstStateMedicalUniversity</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><email xlink:type="simple">zubarovskaya_ls@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1235-4530</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Афанасьев</surname><given-names>Б. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Afanasyev</surname><given-names>B. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доктор медицинских наук, профессор, директор НИИ ДОГиТ им. Р.М. Горбачевой, заведующий кафедрой гематологии, трансфузиологии и трансплантологии ПСПбГМУ им. акад. И.П. Павлова</p><p>197022, Санкт-Петербург, ул. Рентгена, 12</p></bio><bio xml:lang="en"><p>Dr. of Sci. (Med.), Professor, Director of Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, Head of Hematology, Transfusiology and Transpantation Chair at I.P. Pavlov Saint-Petersburg First State Medical University</p><p>12 Rentgena St., Saint Petersburg, 197022</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Научно-исследовательский институт детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Минздрава Росси</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg, Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>19</day><month>09</month><year>2020</year></pub-date><volume>7</volume><issue>3</issue><fpage>13</fpage><lpage>21</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Казанцев И.В., Геворгян А.Г., Юхта Т.В., Толкунова П.С., Козлов А.В., Звягинцева Д.А., Голенкова М.С., Богданова О.И., Швецов А.Н., Морозова Е.В., Николаев И.Ю., Сафонова С.А., Пунанов Ю.А., Зубаровская Л.С., Афанасьев Б.В., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Казанцев И.В., Геворгян А.Г., Юхта Т.В., Толкунова П.С., Козлов А.В., Звягинцева Д.А., Голенкова М.С., Богданова О.И., Швецов А.Н., Морозова Е.В., Николаев И.Ю., Сафонова С.А., Пунанов Ю.А., Зубаровская Л.С., Афанасьев Б.В.</copyright-holder><copyright-holder xml:lang="en">Kazantsev I.V., Gevorgyan A.G., Yukhta T.V., Tolkunova P.S., Kozlov A.V., Zvyagintseva D.A., Golenkova M.S., Bogdanova O.I., Shvetsov A.N., Morozova E.V., Nikolaev I.Y., Safonova S.A., Punanov Y.A., Zubarovskaya L.S., Afanasyev B.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://journal.nodgo.org/jour/article/view/620">https://journal.nodgo.org/jour/article/view/620</self-uri><abstract><sec><title>Введение</title><p>Введение. Нейробластома (НБ) наиболее часто выявляется у детей первых двух лет жизни. В дальнейшем частота выявления НБ значительно меньше и лишь в 1–2 % случаев НБ впервые выявляют у подростков или молодых взрослых. Как правило, заболевание в этой группе пациентов характеризуется рядом биологических особенностей, обусловливающих длительное индолентное течение и неблагоприятный прогноз заболевания. В данной статье представлен анализ серии наблюдений пациентов с НБ, которые на момент постановки диагноза были в возрасте старше 10 лет.</p><p>Описание серии клинических случаев. В период с 2008 по 2019 г. в клинике НИИ ДОГиТ им. Р.М. Горбачевой получали лечение или наблюдались 11 подростков и молодых взрослых с НБ с медианой возраста на момент постановки диагноза 14 (10–28) лет. У 7 из 11 пациентов опухоль локализовалась в заднем средостении, в остальных случаях – в забрюшинном пространстве (n = 2), малом тазу (n = 1), в 1 случае первичный очаг выявить не удалось. У 10 из 11 больных наблюдалась первично-диссеминированная форма НБ с метастатическим поражением лимфатических узлов (n = 5), костей (n = 5), костного мозга (n = 3), печени (n = 1). Морфологическое и цитогенетическое исследования выполнялись у всех пациентов, в 4 наблюдениях дополнительно проводили таргетное секвенирование потенциально патогенных генов. Во всех случаях проводилась химиотерапия согласно рекомендациям для группы высокого риска и применялись методы локального контроля. Семь пациентов дополнительно получили терапию 2–3-й линии. В 7 из 11 наблюдений при достижении ответа выполнена высокодозная полихимиотерапия с аутологичной трансплантацией гемопоэтических стволовых клеток (ауто-ТГСК). При развитии первичной резистентности, прогрессировании или рецидиве заболевания дополнительно применялись таргетная или иммунотерапия, терапия с метайодбензилгуанидином. У 6 больных морфологические характеристики опухоли соответствовали недифференцированной НБ, в 5 случаях – ганглионейробластоме. Описанная серия наблюдений характеризуется рядом особенностей, относящихся к биологическим факторам риска. Амплификация гена MYCN не выявлена ни в одном из случаев, по данным цитогенетического исследования определялись следующие поломки: +2 (n = 2), del1p (n = 1), g17q (n = 1). У всех 4 пациентов, которым выполнялось таргетное секвенирование, выявлены потенциально патогенные мутации: ATRX (у 2 больных в возрасте 19 и 28 лет на момент постановки диагноза), TP53 и PIK3CA, FBXW7. В 9 из 11 случаев зафиксировано первично-резистентное течение заболевания, в 7 наблюдениях ответ достигнут на фоне 2-й и последующих линий терапии. В 2 случаях зафиксирован полный ответ при добавлении к схеме лечения таргетной терапии, в 3 – длительный (16–32 мес) ответ на иммунотерапию. У 6 из 7 пациентов, получивших ауто-ТГСК, в пределах года развился рецидив заболевания. В настоящий момент живы 6 из 11 пациентов. В 2 случаях сохраняется полный ответ по данным сцинтиграфии с 123I-МЙБГ, продолжающийся 86 и 14 мес после завершения терапии соответственно.</p></sec><sec><title>Выводы</title><p>Выводы. Особенности биологических характеристик НБ у подростков и молодых взрослых обусловливают длительное индолентное течение заболевания с высоким риском рецидива. Учитывая высокую частоту развития химиорезистентности в этой группе и значительное число рецидивов после завершения стандартной терапии для группы высокого риска, в их лечении большую роль могут играть таргетная и иммунотерапия.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Neuroblastoma (NB) is the most common extracranial solid tumor in infants, but it is more rarely found in older children. Only 1–2 % of cases are registered in adolescents and young adults. The long-term prognosis in these patients is highly unfavorable due to indolent clinical course formed by peculiar biological characteristics of tumors. We publish a case study of 11 patients with NB older than 10 years at the time of diagnosis.</p></sec><sec><title>Case series description</title><p>Case series description. In 2008 to 2020 a total of 11 adolescent and young adults patients with median age of 14 (10–28) years were treated in Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg. Seven of 11 patients had mediastinal neuroblastoma, in other cases the primary lesion was abdominal (n = 2), pelvic (n = 1), and in one case no primary lesion was defined. Ten of 11 patients had primary disseminated disease with lymph nodes (n = 5), bone (n = 5), bone marrow (n = 3), or hepatic (n = 1) metastases. Tumor morphology and cytogenetics were assessed in all patients, in 4 cases additional targeted sequencing of potentially pathogenic genes was performed. All patients received chemotherapy and local control measures according to high-risk NB guidelines, in 7 of 11 cases additional chemotherapy regimens were used. Seven of 11 patients also received dose-intensive consolidation with autologous hemopoietic stem cell transplantation (auto-HSCT). In case of primary resistance MIBG-therapy, targeted or immunotherapy were used. In 6 cases tumor morphology corresponded to undifferentiated neuroblastoma, in 5 cases to ganglioneuroblastoma. Although all cases were high-risk, they mostly lacked high-risk biological features seen in younger patients. None had MYCN amplification, the cytogenetic assay yielded the following aberrations: +2 (n = 2), del1p (n = 1), g17q (n = 1). All patients, in whom the targeted sequencing was performed had pathogenic mutations: ATRX (in two patients 19 and 28 years at diagnosis), TP53 and PIK3CA, FBXW7. Nine of 11 patients had primary resistant disease, in 7 cases response was obtained on second or subsequent therapy lines. Two patients responded two chemoand targeted therapy combination, in 3 cases monoor combined immunotherapy yielded prolonged (16–32 months) response. Six of 7 auto-HSCT recipients developed a relapse. 6 out of 11 patients are currently alive. In 2 cases, a complete response is maintained according to scintigraphy with 123I-MIBG, lasting 86 and 14 months after completion of therapy.</p></sec><sec><title>Conclusions</title><p>Conclusions. NB is biologically different in adolescents and young adults. It is characterized by indolent clinical course with very high risk of late relapse. As most patients in this group are chemoresistant, the standard dose-intensive tactics may be less effective and perhaps more attention should be given to targeted and immunotherapy-based approaches.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>нейробластома</kwd><kwd>подростки и молодые взрослые</kwd><kwd>высокодозная полихимиотерапия</kwd><kwd>таргетная терапия</kwd><kwd>иммунотерапия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>neuroblastoma</kwd><kwd>adolescents and young adults</kwd><kwd>high-dose chemotherapy</kwd><kwd>targeted therapy</kwd><kwd>immunotherapy</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Mossé Y.P., Deyell R.J., Berthold F., Nagakawara A., Ambros P.F., Monclair T., Cohn S.L., Pearson A.D., London W.B., Matthay K.K. Neuroblastoma in older children, adolescents and young adults: a report from the International Neuroblastoma Risk Group project. Pediatr Blood Cancer 2014;61(4):627–35. doi: 10.1002/pbc.24777.</mixed-citation><mixed-citation xml:lang="en">Mossé Y.P., Deyell R.J., Berthold F., Nagakawara A., Ambros P.F., Monclair T., Cohn S.L., Pearson A.D., London W.B., Matthay K.K. Neuroblastoma in older children, adolescents and young adults: a report from the International Neuroblastoma Risk Group project. Pediatr Blood Cancer 2014;61(4):627–35. doi: 10.1002/pbc.24777.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Spix C., Pastore G., Sankila R., Stiler C.A., Steliarova-Foucher E. Neuroblastoma incidence and survival in European children (1978‒1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006;42(13):2081-91. doi: 10.1016/j.ejca.2006.05.008.</mixed-citation><mixed-citation xml:lang="en">Spix C., Pastore G., Sankila R., Stiler C.A., Steliarova-Foucher E. Neuroblastoma incidence and survival in European children (1978‒1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 2006;42(13):2081-91. doi: 10.1016/j.ejca.2006.05.008.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Cohn S.L., Pearson A.D., London W.B., Monclair T., Ambros P.F., Brodeur G.M., Faldum A., Hero B., Iehara T., Machin D., Mosseri V., Simon T., Garaventa A., Castel V., Matthay K.K. The International Neuroblastoma Risk Group (INRG) Classiﬁcation System: An INRG Task Force Report. J Clin Oncol 2009;27(2):289‒97. doi: 10.1200/JCO.2008.16.6785.</mixed-citation><mixed-citation xml:lang="en">Cohn S.L., Pearson A.D., London W.B., Monclair T., Ambros P.F., Brodeur G.M., Faldum A., Hero B., Iehara T., Machin D., Mosseri V., Simon T., Garaventa A., Castel V., Matthay K.K. The International Neuroblastoma Risk Group (INRG) Classiﬁcation System: An INRG Task Force Report. J Clin Oncol 2009;27(2):289‒97. doi: 10.1200/JCO.2008.16.6785.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Morgenstern D.A., Pötschger U., Moreno L., Papadakis V., Owens C., Ash S., Pasqualini C., Luksch R., Garaventa A., Canete A., Elliot M., Wieczorek A., Laureys G., Kogner P., Malis J., Ruud E., Beck-Popovic M., Schleiermacher G., Valteau-Couanet D., Ladenstein R. Risk stratiﬁcation of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study. Pediatr Blood Cancer 2018;65(11):e27363. doi: 10.1002/pbc.27363.</mixed-citation><mixed-citation xml:lang="en">Morgenstern D.A., Pötschger U., Moreno L., Papadakis V., Owens C., Ash S., Pasqualini C., Luksch R., Garaventa A., Canete A., Elliot M., Wieczorek A., Laureys G., Kogner P., Malis J., Ruud E., Beck-Popovic M., Schleiermacher G., Valteau-Couanet D., Ladenstein R. Risk stratiﬁcation of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study. Pediatr Blood Cancer 2018;65(11):e27363. doi: 10.1002/pbc.27363.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Shinagawa T., Kitamura T., Katanoda K., Matsuda T., Ito Y., Sobue T. The incidence and mortality rates of neuroblastoma cases before and after the cessation of the mass screening program in Japan: A descriptive study. Int J Cancer 2017;140(3):618‒25. doi: 10.1002/ijc.30482.</mixed-citation><mixed-citation xml:lang="en">Shinagawa T., Kitamura T., Katanoda K., Matsuda T., Ito Y., Sobue T. The incidence and mortality rates of neuroblastoma cases before and after the cessation of the mass screening program in Japan: A descriptive study. Int J Cancer 2017;140(3):618‒25. doi: 10.1002/ijc.30482.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Conte M., Parodi S., De Bernardi B., Milanaccio C., Mazzocco K., Angelini P., Viscardi E., Di Cataldo A., Luksch R., Haupt R. Neuroblastoma in adolescents: the Italian experience. Cancer 2006;106(6):1409‒17. doi: 10.1002/cncr.21751.</mixed-citation><mixed-citation xml:lang="en">Conte M., Parodi S., De Bernardi B., Milanaccio C., Mazzocco K., Angelini P., Viscardi E., Di Cataldo A., Luksch R., Haupt R. Neuroblastoma in adolescents: the Italian experience. Cancer 2006;106(6):1409‒17. doi: 10.1002/cncr.21751.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Duan X.F., Zhao Q. TERT-mediated and ATRX-mediated Telomere Maintenance and Neuroblastoma. J Pediatr Hematol Oncol 2018;40(1):1‒6. doi: 10.1097/MPH.0000000000000840.</mixed-citation><mixed-citation xml:lang="en">Duan X.F., Zhao Q. TERT-mediated and ATRX-mediated Telomere Maintenance and Neuroblastoma. J Pediatr Hematol Oncol 2018;40(1):1‒6. doi: 10.1097/MPH.0000000000000840.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Suzuki M., Kushner B.H., Kramer K., Basu E.M., Roberts S.S., Hammond W.J., LaQuaglia M.P., Wolden S.L., Cheung N.K.V., Modak S. Treatment and Outcome of Adult-Onset Neuroblastoma. Int J Cancer 2018;143(5):1249‒58. doi: 10.1002/ijc.31399.</mixed-citation><mixed-citation xml:lang="en">Suzuki M., Kushner B.H., Kramer K., Basu E.M., Roberts S.S., Hammond W.J., LaQuaglia M.P., Wolden S.L., Cheung N.K.V., Modak S. Treatment and Outcome of Adult-Onset Neuroblastoma. Int J Cancer 2018;143(5):1249‒58. doi: 10.1002/ijc.31399.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Kazantsev I.V., Iukhta T.V., Gevorgian A.G., Tolkunova P.S., Shamin A.V., Baykov V.V., Vorobyov A.V., Kozlov A.V., Karsakova M.A., Kuga P.S., Shvetsov A.N., Morozova E.V., Safonova S.A., Punanov Yu.A., Zubarovskaya L.S., Afanasyev B.V. A long-term response to allogeneic hemopoietic stem cell transplantation from haploidentical donor and post-transplant therapy in an adolescent with primary resistant neuroblastoma. Cellular Therapy and Transplantation 2020;9(2):71‒6. doi: 10.18620/ctt-1866-8836-2020-9-2-71-77.</mixed-citation><mixed-citation xml:lang="en">Kazantsev I.V., Iukhta T.V., Gevorgian A.G., Tolkunova P.S., Shamin A.V., Baykov V.V., Vorobyov A.V., Kozlov A.V., Karsakova M.A., Kuga P.S., Shvetsov A.N., Morozova E.V., Safonova S.A., Punanov Yu.A., Zubarovskaya L.S., Afanasyev B.V. A long-term response to allogeneic hemopoietic stem cell transplantation from haploidentical donor and post-transplant therapy in an adolescent with primary resistant neuroblastoma. Cellular Therapy and Transplantation 2020;9(2):71‒6. doi: 10.18620/ctt-1866-8836-2020-9-2-71-77.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Suzuki M., Kushner B.H., Kramer K., Roberts S.S., LaQuaglia M.P., Cheung N.K.V., Modak S. Anti-GD2 immunotherapy in adults with high-risk neuroblastoma (HR-NB): The Memorial Sloan Kettering Cancer Center (MSKCC) experience. J Clin Oncol 2017;35(15_s):10550. doi: 10.1200/JCO.2017.35.15_suppl.10550.</mixed-citation><mixed-citation xml:lang="en">Suzuki M., Kushner B.H., Kramer K., Roberts S.S., LaQuaglia M.P., Cheung N.K.V., Modak S. Anti-GD2 immunotherapy in adults with high-risk neuroblastoma (HR-NB): The Memorial Sloan Kettering Cancer Center (MSKCC) experience. J Clin Oncol 2017;35(15_s):10550. doi: 10.1200/JCO.2017.35.15_suppl.10550.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Hertwig F., Peifer M., Fischer M. Telomere maintenance is pivotal for high-risk neuroblastoma. Cell Cycle 2016;15(3):311‒2. doi: 10.1080/15384101.2015.1125243.</mixed-citation><mixed-citation xml:lang="en">Hertwig F., Peifer M., Fischer M. Telomere maintenance is pivotal for high-risk neuroblastoma. Cell Cycle 2016;15(3):311‒2. doi: 10.1080/15384101.2015.1125243.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Zeineldin M., Federico S., Chen X., Fan Y., Xu B., Steward E., Zhou X., Jeon J., Griﬃths L., Nguyen R., Norrie J., Easton J., Mulder H., Yergeau D., Liu Y., Wu J., Van Ryn C., Naranjo A., Hogarty M.D., Kamiński M.M., Valentine M., Pruett-Miller S.M., Pappo A., Zhang J., Clay M.R., Bahrami A., Vogel P., Lee S., Shelat A., Sarthy J.F., Meers M.P., George R.E., Mardis E.R., Wilson R.K., Henikoﬀ S., Downing J.R., Dyer M.A. MYCN ampliﬁcation and ATRX mutations are incompatible in neuroblastoma. Nat Commun 2020;11(1):913. doi: 10.1038/s41467-020-14682-6.</mixed-citation><mixed-citation xml:lang="en">Zeineldin M., Federico S., Chen X., Fan Y., Xu B., Steward E., Zhou X., Jeon J., Griﬃths L., Nguyen R., Norrie J., Easton J., Mulder H., Yergeau D., Liu Y., Wu J., Van Ryn C., Naranjo A., Hogarty M.D., Kamiński M.M., Valentine M., Pruett-Miller S.M., Pappo A., Zhang J., Clay M.R., Bahrami A., Vogel P., Lee S., Shelat A., Sarthy J.F., Meers M.P., George R.E., Mardis E.R., Wilson R.K., Henikoﬀ S., Downing J.R., Dyer M.A. MYCN ampliﬁcation and ATRX mutations are incompatible in neuroblastoma. Nat Commun 2020;11(1):913. doi: 10.1038/s41467-020-14682-6.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Duan K., Dickson B.C., Marrano P., Thorner P.S., Chung C.T. Adult-onset neuroblastoma: Report of seven cases with molecular genetic characterization. Genes Chromosomes Cancer 2020;59(4):240‒8. doi: 10.1002/gcc.22826.</mixed-citation><mixed-citation xml:lang="en">Duan K., Dickson B.C., Marrano P., Thorner P.S., Chung C.T. Adult-onset neuroblastoma: Report of seven cases with molecular genetic characterization. Genes Chromosomes Cancer 2020;59(4):240‒8. doi: 10.1002/gcc.22826.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Ikegaki N., Shimada H; International Neuroblastoma Pathology Committee. Subgrouping of Unfavorable Histology Neuroblastomas With Immunohistochemistry Toward Precision Prognosis and Therapy Stratiﬁcation. JCO Precis Oncol 2019;3:10.1200/PO.18.00312. doi: 10.1200/PO.18.00312.</mixed-citation><mixed-citation xml:lang="en">Ikegaki N., Shimada H; International Neuroblastoma Pathology Committee. Subgrouping of Unfavorable Histology Neuroblastomas With Immunohistochemistry Toward Precision Prognosis and Therapy Stratiﬁcation. JCO Precis Oncol 2019;3:10.1200/PO.18.00312.  doi: 10.1200/PO.18.00312.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Казанцев И.В., Геворгян А.Г., Юхта Т.В., Толкунова П.С., Звягинцева Д.А., Козлов А.В., Голенкова М.С., Бабенко Е.В., Куга П.С., Швецов А.Н., Николаев И.Ю., Морозова Е.В., Сафонова С.А., Пунанов Ю.А., Зубаровская Л.С., Афанасьев Б.В. Интенсивная комплексная терапия пациентов с первично-резистентным течением и рецидивами нейробластомы: опыт НИИ ДОГиТ им. Р.М. Горбачевой. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2020;19(2):129‒40. doi: 10.24287/1726-1708-2020-19-2-129-140.</mixed-citation><mixed-citation xml:lang="en">Kazantsev I.V., Gevorgyan A.G., Yukhta T.V., Tolkunova P.S., Zvyagintseva D.A., Kozlov A.V., Golenkova M.S., Babenko E.V., Kuga P.S., Shvetsov A.N., Nikolaev I.Yu., Morozova E.V., Safonova S.A., Punanov Yu.A., Zubarovskaya L.S., Afanasyev B.V. The complex intensive therapy regimen as curative therapy in patients with primary-resistant and relapsed neuroblastoma: R.M. Gorbacheva Memorial Institute for Children Oncology, Hematology and Transplantation experience. Voprosy gematologii/onkologii i immunopatologii v pediatrii = Pediatric Hematology/Oncology and Immunopathology 2020;19(2):129‒40. (In Russ.). doi: 10.24287/1726-1708-2020-19-2-129-140.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Umpathy G., Mendoza-Garcia P., Hallberg B., Palmer R.H. Targeting anaplastic lymphoma kinase in neuroblastoma. APMIS 2019;127(5):288‒302. doi: 10.1111/apm.12940.</mixed-citation><mixed-citation xml:lang="en">Umpathy G., Mendoza-Garcia P., Hallberg B., Palmer R.H. Targeting anaplastic lymphoma kinase in neuroblastoma. APMIS 2019;127(5):288‒302. doi: 10.1111/apm.12940.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Vasseur A., Cabel L., Geiss R., Schleiermacher G., Pierron G., Kamal M., Jehanno N., Bataillon G., Guinebretiere J.M., Bozec L. Eﬃcacy of Lorlatinib in Primary Crizotinib-Resistant Adult Neuroblastoma Harboring ALKY1278S Mutation. JCO Precis Oncol 2019;3:1‒5. doi: 10.1200/PO.18.00396.</mixed-citation><mixed-citation xml:lang="en">Vasseur A., Cabel L., Geiss R., Schleiermacher G., Pierron G., Kamal M., Jehanno N., Bataillon G., Guinebretiere J.M., Bozec L. Eﬃcacy of Lorlatinib in Primary Crizotinib-Resistant Adult Neuroblastoma Harboring ALKY1278S Mutation. JCO Precis Oncol 2019;3:1‒5. doi: 10.1200/PO.18.00396.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
