ОБЗОРЫ

Стратификация пациентов cо множественной миеломой: современное состояние вопроса и дальнейшие перспективы

ОБЗОРЫ , , , , ,

А.Ю. Аксенова1, А.С. Жук2, Е.И. Степченкова1,3, С.В. Грицаев4

1 ФГБОУ ВО «Санкт-Петербургский государственный университет», Университетская наб., д. 7/9, Санкт-Петербург, Российская Федерация, 199034

2 ФГАОУ ВО «Национальный исследовательский университет ИТМО», Кронверкский пр-т, д. 49, лит. А, Санкт-Петербург, Российская Федерация, 197101

3 ФГБУН «Институт общей генетики им. Н.И. Вавилова РАН», Санкт-Петербургский филиал, Университетская наб., д. 7/9, Санкт-Петербург, Российская Федерация, 199034

4 ФГБУ «Российский НИИ гематологии и трансфузиологии ФМБА России», ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024

Для переписки: Анна Юрьевна Аксенова, канд. биол. наук, ул. Ботаническая, д. 17, Санкт-Петербург, Российская Федерация, 198504; тел.: +7(812)428-40-09; e-mail: a.aksenova@spbu.ru; Сергей Васильевич Грицаев, д-р мед. наук, ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024; тел.: +7(812)717-54-68; e-mail: gritsaevsv@mail.ru

Для цитирования: Аксенова А.Ю., Жук А.С., Степченкова Е.И., Грицаев С.В. Стратификация пациентов cо множественной миеломой: современное состояние вопроса и дальнейшие перспективы. Клиническая онкогематология. 2022;15(3):259–70.

DOI: 10.21320/2500-2139-2022-15-3-259-270

РЕФЕРАТ

В последние годы наблюдается существенный прогресс в улучшении выживаемости без прогрессирования (ВБП) и качества жизни пациентов со множественной миеломой (ММ). Это стало возможным благодаря внедрению в клиническую практику новых препаратов, разработанных с учетом данных мультиомиксных молекулярно-генетических исследований при ММ. Результаты этих исследований позволили также оценить уровень генетической гетерогенности опухолевых клеток при ММ. Так, были выявлены типы и частота однонуклеотидных вариаций, структурных изменений хромосом и нарушений копийности хромосом, встречающихся в геноме злокачественных плазматических клеток. Показано, что у разных пациентов с ММ существенно отличается спектр выявляемых генетических нарушений в опухоли. Высокая генетическая гетерогенность заболевания служит одной из главных причин различной эффективности лекарственных препаратов и различий в ВБП. В настоящем обзоре подробно рассматривается вопрос о значении ряда хромосомных аберраций для распределения больных ММ по группам риска. Представлено описание наиболее частых аберраций, в т. ч. с высоким и низким риском раннего прогрессирования ММ, уже включенных в различные международные прогностические шкалы. Кроме того, определены дополнительные аберрации, которые обладают потенциалом для применения в клинической практике. Особое внимание уделяется проблеме оценки риска при обнаружении нескольких различных хромосомных перестроек у одного пациента. В обзоре описаны трудности и перспективы использования информации о хромосомных перестройках для выбора наиболее оптимальных схем лечения и оценки их эффективности. В этом контексте важное значение придается проблемам интеграции генетических данных и таких клинических показателей, как возраст больного, сопутствующие заболевания, почечная дисфункция, степень поражения костей, показания к трансплантации аутологичных гемопоэтических стволовых клеток и др.

Ключевые слова: множественная миелома, международные системы стадирования, хромосомные перестройки, R-ISS, R2-ISS, mSMART, MASS.

Получено: 28 марта 2022 г.

Принято в печать: 5 июня 2022 г.

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Статистика Plumx русский

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Фармакоэкономический анализ терапии CAR Т-клетками при диффузной В-крупноклеточной лимфоме и В-линейных острых лимфобластных лейкозах

ОБЗОРЫ , , , , , ,

И.В. Грибкова, А.А. Завьялов

ГБУ «НИИ организации здравоохранения и медицинского менеджмента ДЗМ», ул. Шарикоподшипниковская, д. 9, Москва, Российская Федерация, 115088

Для переписки: Ирина Владимировна Грибкова, канд. биол. наук, ул. Шарикоподшипниковская, д. 9, Москва, Российская Федерация, 115088; тел.: +7(916)078-73-90; e-mail: igribkova@yandex.ru

Для цитирования: Грибкова И.В., Завьялов А.А. Фармакоэкономический анализ терапии CAR Т-клетками при диффузной В-крупноклеточной лимфоме и В-линейных острых лимфобластных лейкозах. Клиническая онкогематология. 2022;15(2):205–12.

DOI: 10.21320/2500-2139-2022-15-2-205-212

РЕФЕРАТ

Генетически модифицированные Т-лимфоциты с химерными антигенными рецепторами (CAR T-клетки) представляют собой новую стратегию лечения пациентов с рецидивами или рефрактерным течением В-клеточных злокачественных новообразований. В 2017–2018 гг. два препарата CAR T-клеточной терапии: тисагенлеклейсел и аксикабтаген силолейсел — были одобрены Управлением по контролю за качеством пищевых продуктов и лекарственных средств США (FDA) и Европейским агентством по лекарственным средствам (EMA) для клинического применения у пациентов с рефрактерным острым лимфобластным лейкозом и рецидивами/рефрактерными В-клеточными лимфомами. К настоящему времени CAR Т-клеточная терапия все более становится неотъемлемой частью клинической практики благодаря своей высокой эффективности. Однако стоимость этого метода противоопухолевого воздействия чрезвычайно высока. Средняя стоимость тисагенлеклейсела составляет 475 000 долларов США ($), а аксикабтагена силолейсела — 373 000 $. Следует отметить, что это только цены на лекарственные препараты без учета других затрат, связанных с данным методом терапии. В работах 2018–2020 гг. группы исследователей предприняли попытки оценить затраты, связанные с CAR T-клеточной терапией. Цель настоящего обзора — анализ этих исследований, оценка общей стоимости терапии и структуры затрат, рассмотрение факторов, ведущих к увеличению затрат, обсуждение возможности повышения доступности технологии CAR-T в целом. Результаты показали, что в среднем общая стоимость терапии тисагенлеклейселом при В-клеточной лимфоме составила 515 150 $, аксикабтагеном силолейселом — 503 955 $. Стоимость терапии острого лимфобластного лейкоза составила 580 459 $. Основными факторами, влияющими на общую стоимость лечения, были цены на препараты CAR T-клеток, высокая степень тяжести нежелательных явлений и большая опухолевая нагрузка до инфузии CAR T-клеточного продукта. Признается, что в качестве основных возможностей повышения доступности терапии CAR T-клетками может служить понижение цены на препараты (например, за счет собственного производства на базе медицинского учреждения), дальнейшее совершенствование терапии с целью снизить ее токсичность, а также применение на ранних стадиях опухолевого заболевания.

Ключевые слова: В-клеточная лимфома, острый лимфобластный лейкоз, CAR T-клеточная терапия, химерный антигенный рецептор, тисагенлеклейсел, аксикабтаген силолейсел, затраты, обзор.

Получено: 29 октября 2021 г.

Принято в печать: 15 февраля 2022 г.

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Статистика Plumx русский

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Искусственный интеллект в гематологии

ОБЗОРЫ ,

Искусственный интеллект не заменит врача, однако врачи, использующие искусственный

интеллект, заменят тех, кто его не использует.

Dr. Bertalan Mesko, медицинский футурист

А.С. Лучинин

ФГБУН «Кировский НИИ гематологии и переливания крови ФМБА», ул. Красноармейская, д. 72, Киров, Российская Федерация, 610027

Для переписки: Александр Сергеевич Лучинин, канд. мед. наук, ул. Красноармейская, д. 72, Киров, Российская Федерация, 610027; тел.: +7(919)506-87-86; e-mail: glivec@mail.ru

Для цитирования: Лучинин А.С. Искусственный интеллект в гематологии. Клиническая онкогематология. 2022;15(1):16–27.

DOI: 10.21320/2500-2139-2022-15-1-16-27

РЕФЕРАТ

«Искусственный интеллект» — это общий термин, описывающий компьютерные технологии для решения задач, которые требуют применения интеллекта человека, например распознавание человеческого голоса или изображений. Большинство продуктов с использованием искусственного интеллекта, применяемых в здравоохранении, связано с машинным обучением — отраслью информатики и статистики, которая генерирует предсказательные или описательные модели путем обучения на основе данных, а не путем программирования четких правил. Машинное обучение получило широкое распространение в патоморфологии, радиологии, геномике и анализе данных электронных медицинских карт. С учетом имеющейся тенденции технологии искусственного интеллекта, вероятно, будут все больше интегрироваться в исследовательскую и практическую медицину, включая гематологию. Таким образом, искусственный интеллект и машинное обучение заслуживают внимания и понимания со стороны исследователей и клиницистов. В данном обзоре описываются важные терминологические понятия и основные концепции обозначенных технологий, а также приводятся примеры их практического использования в научной и практической работе врача-гематолога.

Ключевые слова: искусственный интеллект, машинное обучение, нейронная сеть.

Получено: 23 сентября 2021 г.

Принято в печать: 15 декабря 2021 г.

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Статистика Plumx русский

ЛИТЕРАТУРА

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Гистиоцитоз из клеток Лангерганса у взрослых: современные возможности терапии

ОБЗОРЫ , ,

В.Д. Латышев, Е.А. Лукина

ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167

Для переписки: Виталий Дмитриевич Латышев, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; e-mail: LatyshevVD@gmail.com

Для цитирования: Латышев В.Д., Лукина Е.А. Гистиоцитоз из клеток Лангерганса у взрослых: современные возможности терапии. Клиническая онкогематология. 2021;14(4):444–54.

DOI: 10.21320/2500-2139-2021-14-4-444-454

РЕФЕРАТ

Гистиоцитоз из клеток Лангерганса (ГКЛ) — крайне редкое заболевание, обусловленное тканевой инфильтрацией патологическими клетками, имеющими фенотипическое сходство с нормальными клетками Лангерганса. Стандартная терапия ГКЛ у взрослых до настоящего времени не разработана ввиду отсутствия достаточной доказательной базы для тех или иных методов лечения. В клинической практике находит применение как цитостатическое лечение, так и новые подходы с использованием ингибиторов сигнальных путей, вовлеченных в патогенез ГКЛ. Настоящий литературный обзор посвящен существующим на текущий момент методам терапии ГКЛ у взрослых пациентов и возможностям их применения в клинической практике.

Ключевые слова: гистиоцитоз из клеток Лангерганса, терапия гистиоцитозов, мутация BRAFV600E, MAPK.

Получено: 20 июля 2021 г.

Принято в печать: 23 сентября 2021 г.

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Статистика Plumx русский

ЛИТЕРАТУРА

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Молекулярное профилирование и мониторинг минимальной остаточной болезни у больных множественной миеломой: обзор литературы

ОБЗОРЫ ,

А.В. Семьянихина1,2, Е.Э. Толстых1

1 ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

2 ФГБНУ «Медико-генетический научный центр им. акад. Н.П. Бочкова», ул. Москворечье, д. 1, Москва, Российская Федерация, 115522

Для переписки: Александра Владимировна Семьянихина, канд. мед. наук, Каширское ш., д. 23, Moсква, Российская Федерация, 115478; тел.: +7(926)371-21-56; e-mail: alexandra_silina@mail.ru

Для цитирования: Семьянихина А.В., Толстых Е.Э. Молекулярное профилирование и мониторинг минимальной остаточной болезни у больных множественной миеломой: обзор литературы. Клиническая онкогематология. 2021;14(4):436–43.

DOI: 10.21320/2500-2139-2021-14-4-436-443

РЕФЕРАТ

Персонализированный подход выступает многообещающим инструментом в терапии злокачественных новообразований (ЗНО). Достижение успехов и оценка преимуществ такого подхода были значительно форсированы внедрением технологий секвенирования нового поколения, позволяющих получать полную информацию о состоянии генома и транскриптома опухоли с выявлением потенциальных биомаркеров и мишеней для направленного лекарственного воздействия. Несмотря на экспоненциальный рост секвенированных опухолевых геномов, ряд ЗНО остается вне активной фазы клинических исследований при очевидных и растущих потребностях в оптимизации существующих схем лечения. Одной из таких патологий является множественная миелома (ММ). Значительные достижения в диагностике и лечении ММ позволили существенно повысить показатели выживаемости при этой злокачественной опухоли. Однако исключить ММ из списка неизлечимых заболеваний пока не удается. ММ остается неоплазией, требующей разработки и внедрения новых лечебных подходов, большинство из которых будет базироваться на фено- и генотипических особенностях опухолевых клеток. Настоящий обзор посвящен современному состоянию изучения молекулярно-генетического профиля ММ, мониторинга минимальной остаточной болезни (МОБ), а также возможностей секвенирования нового поколения для диагностики, прогноза, оценки МОБ и поиска предикторов с целью оптимизации противоопухолевого лечения.

Ключевые слова: множественная миелома, секвенирование нового поколения, минимальная остаточная болезнь.

Получено: 21 мая 2021 г.

Принято в печать: 29 августа 2021 г.

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Статистика Plumx русский

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Биологические механизмы сохранения глубокого молекулярного ответа при хроническом миелолейкозе после отмены ингибиторов тирозинкиназ

ОБЗОРЫ , , ,

Е.Ю. Челышева, М.А. Гурьянова, А.Г. Туркина

ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167

Для переписки: Екатерина Юрьевна Челышева, канд. мед. наук, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; e-mail: denve@bk.ru

Для цитирования: Челышева Е.Ю., Гурьянова М.А., Туркина А.Г. Биологические механизмы сохранения глубокого молекулярного ответа при хроническом миелолейкозе после отмены ингибиторов тирозинкиназ. Клиническая онкогематология. 2021;14(4):427–35.

DOI: 10.21320/2500-2139-2021-14-4-427-435

РЕФЕРАТ

Возможность наблюдения без лечения у пациентов с хроническим миелолейкозом (ХМЛ) в эру ингибиторов тирозинкиназ (ИТК) остается актуальным вопросом. В клинических исследованиях по отмене ИТК при стабильном глубоком молекулярном ответе показана вероятность сохранения молекулярной ремиссии у 40–60 % больных. Сохранение ремиссии без лечения (РБЛ) даже при персистировании остаточных лейкозных клеток свидетельствует о том, что существуют особые, биологически обусловленные механизмы контроля пролиферации опухолевых клеток, не зависящие от BCR-ABL-киназной активности. Поиск факторов, которые определяют различия кинетики остаточного лейкозного клона после отмены ИТК, — важная задача для понимания основ РБЛ как нового биологического явления. В обзоре представлены сведения мировой литературы, касающиеся изучения иммунных, генетических и других биологических механизмов, лежащих в основе контроля минимальной остаточной болезни после отмены ИТК у больных ХМЛ.

Ключевые слова: хронический миелолейкоз, ингибиторы тирозинкиназ, ремиссия без лечения, глубокий молекулярный ответ, минимальная остаточная болезнь.

Получено: 10 мая 2021 г.

Принято в печать: 23 августа 2021 г.

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Статистика Plumx русский

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Инфекционные осложнения при множественной миеломе в условиях современной эпидемиологической обстановки: обзор литературы

ОБЗОРЫ , ,

И.Л. Давыдкин, Е.В. Мордвинова, Т.П. Кузьмина

ФГБОУ ВО «Самарский государственный медицинский университет» Минздрава России, ул. Чапаевская, д. 89, Самара, Российская Федерация, 443099

Для переписки: Елизавета Владимировна Мордвинова, ул. Чапаевская, д. 89, Самара, Российская Федерация, 443099; тел.: +7(917)037-52-10, e-mail: liza.mordvinova.94@mail.ru

Для цитирования: Давыдкин И.Л., Мордвинова Е.В., Кузьмина Т.П. Инфекционные осложнения при множественной миеломе в условиях современной эпидемиологической обстановки: обзор литературы. Клиническая онкогематология. 2021;14(3):386–90.

DOI: 10.21320/2500-2139-2021-14-3-386-390

РЕФЕРАТ

Обзор посвящен современным представлениям об иммунной системе при множественной миеломе (ММ) и основных патогенах, приводящих к инфекционным осложнениям в данной группе пациентов. Несмотря на то что за последние годы достигнут значительный прогресс в исследовании молекулярных механизмов становления и развития (патогенеза) ММ, методов ее диагностики, а также в прогнозировании исходов и лечении, одной из основных причин летальности у этой категории пациентов остаются инфекционные осложнения. В такой ситуации представляется актуальным дальнейшее изучение нарушений в иммунной системы и спектра инфекционных патогенов, распространенных в когорте пациентов с ММ. Исследование и коррекция иммунного статуса пациентов могут способствовать улучшению исхода ММ, что, в свою очередь, приведет к увеличению продолжительности жизни.

Ключевые слова: множественная миелома, иммунный статус, инфекционные осложнения, COVID-19.

Получено: 12 марта 2021 г.

Принято в печать: 8 июня 2021 г.

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Воспалительный синдром восстановления иммунитета и лимфома Ходжкина

ОБЗОРЫ ,

А.В. Пивник1, А.М. Вукович2, А.А. Петренко3,4

1 СМ-клиника, Волгоградский пр-т, д. 42, корп. 12, Москва, Российская Федерация, 109548

2 ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России, ул. Трубецкая, д. 8, стр. 2, Москва, Российская Федерация, 119991

3 ГБУЗ «Городская клиническая больница им. С.П. Боткина» ДЗМ, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284

4 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, ул. Баррикадная, д. 2/1, Москва, Российская Федерация, 125993

Для переписки: Александр Васильевич Пивник, д-р мед. наук, профессор, Волгоградский пр-т, д. 42, корп. 12, Москва, Российская Федерация, 109548; тел.: +7(906)065-99-32; e-mail: pivnikav@gmail.com

Для цитирования: Пивник А.В., Вукович А.М., Петренко А.А. Воспалительный синдром восстановления иммунитета и лимфома Ходжкина. Клиническая онкогематология. 2021;14(3):378–85.

DOI: 10.21320/2500-2139-2021-14-3-378-385

РЕФЕРАТ

Воспалительный синдром восстановления иммунитета (ВСВИ) определяется как клинически значимое обострение известных малосимптомных серьезных, чаще инфекционных, заболеваний в условиях значительного повышения уровня Т-лимфоцитов CD4+ в ответ на высокоактивную антиретровирусную терапию (ВААРТ) ВИЧ-инфекции. В обзоре подробно обсуждается проблема туберкулеза у ВИЧ-инфицированных пациентов, получающих ВААРТ. В рекомендациях на эту тему имеются строгие указания на обязательное первоначальное лечение туберкулеза и только затем назначение ВААРТ. Такие же рекомендации по этиотропной терапии, предшествующей ВААРТ, предусмотрены при других оппортунистических инфекциях (грибковых, криптококковой, паразитозах, контагиозном моллюске, токсоплазмозе, вирусе опоясывающего лишая, лейшманиозе, сифилисе, лепре). Без предшествующей этиотропной терапии оппортунистической инфекции ее обострение с выраженной клинической картиной в период проведения ВААРТ может иметь фатальные последствия для пациента. Лимфомы, включая лимфому Ходжкина (ЛХ), рассматриваются в рамках именно этой проблемы. Однако остаются открытыми вопросы специфичности направленного действия Т-лимфоцитов микроокружения к не выясненным до настоящего времени причинным антигенам опухоли. В отличие от других злокачественных лимфоидных опухолей, которые возникают при низком содержании Т-лимфоцитов CD4+, ЛХ развивается при повышенном уровне Т-лимфоцитов CD4+ в ответ на ВААРТ у ВИЧ-инфицированных пациентов в первые месяцы от начала антиретровирусного лечения. ЛХ диагностируется у 8 % ВИЧ-инфицированных лиц без ВААРТ. После назначения ВААРТ частота ЛХ возрастает до 17 %. Эти данные позволяют рассматривать ВСВИ в качестве основной проблемы при изучении этиологии и патогенеза ЛХ у ВИЧ-инфицированных пациентов. В такой ситуации необходимость продолжения исследований в этом направлении становится не только очевидной, но и практически востребованной.

Ключевые слова: воспалительный синдром восстановления иммунитета (ВСВИ), высокоактивная антиретровирусная терапия (ВААРТ), лимфома Ходжкина.

Получено: 19 января 2021 г.

Принято в печать: 22 апреля 2021 г.

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Множественная миелома и вакцины на основе дендритных клеток

ОБЗОРЫ , , ,

И.В. Грибкова, А.А. Завьялов

ГБУ «НИИ организации здравоохранения и медицинского менеджмента ДЗМ», ул. Шарикоподшипниковская, д. 9, Москва, Российская Федерация, 115088

Для переписки: Ирина Владимировна Грибкова, канд. биол. наук, ул. Шарикоподшипниковская, д. 9, Москва, Российская Федерация, 115088; тел.: +7(916)078-73-90; e-mail: igribkova@yandex.ru

Для цитирования: Грибкова И.В., Завьялов А.А. Множественная миелома и вакцины на основе дендритных клеток. Клиническая онкогематология. 2021;14(3):370–7.

DOI: 10.21320/2500-2139-2021-14-3-370-377

РЕФЕРАТ

Несмотря на успехи, достигнутые в лечении множественной миеломы, у большинства пациентов после его окончания сохраняется минимальная остаточная болезнь (МОБ-положительный статус), что повышает риск развития рецидива. Антигенспецифическая иммунотерапия опухолей позволяет улучшить клинический исход у таких пациентов за счет уничтожения устойчивого к лекарственному противоопухолевому воздействию клона опухолевых клеток без повреждения нормальных тканей. Дендритные клетки (ДК) представляют собой антигенпрезентирующие элементы, главной функцией которых является захват антигенов, процессинг и представление их наивным Т-лимфоцитам для активации иммунного ответа против захваченного антигена. Уникальные способности ДК активировать Т-хелперы, а также цитотоксические Т-лимфоциты и посредством этого определять направленность иммунных реакций использовались для разработки иммунотерапии опухолей на основе ДК. Такой подход предполагает применение так называемых ДК-вакцин. К настоящему времени уже имеются результаты клинических исследований по использованию ДК-вакцин при различных опухолях, включая гематологические. В целом, согласно проведенным испытаниям, ДК-вакцины характеризуются удовлетворительным профилем безопасности, умеренной иммунной активностью и умеренной клинической эффективностью. В настоящем обзоре рассматриваются результаты клинических исследований по использованию вакцин на основе ДК у больных множественной миеломой. Кроме того, обсуждаются возможности повышения клинической эффективности данной терапии.

Ключевые слова: множественная миелома, дендритные клетки, ДК-вакцины, гематологические злокачественные новообразования, иммунотерапия.

Получено: 9 марта 2021 г.

Принято в печать: 11 июня 2021 г.

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Статистика Plumx русский

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Лечение пациентов с мастоцитозом: обзор литературы

ОБЗОРЫ , , , , ,

К.М. Чернавина1, А.С. Орлова1, Е.А. Никитин2

1 ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России, ул. Трубецкая, д. 8, стр. 2, Москва, Российская Федерация, 119991

2 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, ул. Баррикадная, д. 2/1, Москва, Российская Федерация, 125993

Для переписки: Карина Максимовна Чернавина, ул. Трубецкая, д. 8, стр. 2, Москва, Российская Федерация, 119992; e-mail: Shkyrlak@gmail.com

Для цитирования: Чернавина К.М., Орлова А.С., Никитин Е.А. Лечение пациентов с мастоцитозом: обзор литературы. Клиническая онкогематология. 2021;14(3):361–9.

DOI: 10.21320/2500-2139-2021-14-3-361-369

РЕФЕРАТ

Термин «мастоцитоз» объединяет группу редких гетерогенных расстройств, возникающих в результате пролиферации и накопления неопластических тучных клеток в различных органах. Согласно классификации Всемирной организации здравоохранения (ВОЗ), выделяют три вида заболевания: кожный мастоцитоз, системный мастоцитоз (СМ) и тучноклеточная саркома (ТКС). СМ в зависимости от степени агрессивности может быть индолентным, тлеющим, агрессивным (АСМ) или ассоциированным с другим пролиферативным гематологическим заболеванием нетучноклеточной линии (СМ-АГЗ). СМ также включает тучноклеточный лейкоз (ТКЛ). В многочисленных исследованиях подтверждается прогностическое значение классификации ВОЗ. Все пациенты с мастоцитозом нуждаются в лечении, направленном на купирование симптомов активации тучных клеток. При прогностически неблагоприятных формах мастоцитоза, таких как АСМ, СМ-АГЗ, ТКЛ и ТКС, также необходимо рассмотреть более интенсивные методы лечения, включающие применение трансплантации аллогенных гемопоэтических стволовых клеток, циторедуктивной терапии ингибиторами тирозинкиназ (ИТК), интерфероном-α и кладрибином. Ведущую роль в патогенезе мастоцитоза занимают мутации в различных экзонах гена KIT. Наиболее часто обнаруживается активирующая мутация KITD816V (80–90 % случаев СМ). Разработан ряд ИТК, некоторые из которых (иматиниба мезилат и мидостаурин) успешно использовались в рамках клинических исследований и были одобрены для лечения пациентов с прогностически неблагоприятными формами мастоцитоза. Однако применение только ИТК не обеспечивает длительную ремиссию заболевания у ряда пациентов ввиду развития резистентности к лечению, обусловленной активирующими мутациями KIT, а также наличием других дополнительных соматических мутаций и молекулярных изменений. В обзоре для сравнительной оценки приводятся результаты наиболее крупных клинических исследований, касающихся различных методов лечения пациентов с мастоцитозом.

Ключевые слова: тучные клетки, мастоцитоз, мутация KITD816V, таргетное лечение, ингибиторы тирозинкиназ, иматиниб, мидостаурин.

Получено: 12 марта 2021 г.

Принято в печать: 10 июня 2021 г.

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