ОБЗОРЫ

KIR-генетические факторы и ответ на терапию ингибиторами тирозинкиназ при хроническом миелоидном лейкозе

ОБЗОРЫ , , ,

Е.В. Кузьмич1, И.Е. Павлова1, Л.Н. Бубнова1,2, С.С. Бессмельцев1

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

2 ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

Для переписки: Елена Витальевна Кузьмич, канд. биол. наук, ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024; тел.: +7(921)912-52-07; e-mail: yelenakuzmich@gmail.com

Для цитирования: Кузьмич Е.В., Павлова И.Е., Бубнова Л.Н., Бессмельцев С.С. KIR-генетические факторы и ответ на терапию ингибиторами тирозинкиназ при хроническом миелоидном лейкозе. Клиническая онкогематология. 2023;16(2):119–27.

DOI: 10.21320/2500-2139-2023-16-2-119-127

РЕФЕРАТ

Разработка и внедрение в клиническую практику ингибиторов тирозинкиназ (ИТК) значительно улучшили прогноз у пациентов с хроническим миелоидным лейкозом (ХМЛ). Примерно 50 % пациентов, достигающих глубокого молекулярного ответа, могут быть кандидатами на безопасное прекращение приема ИТК. Несмотря на достигнутые результаты, до настоящего времени не существует надежных биомаркеров для прогнозирования ответа и сохранения ремиссии без лечения после прекращения приема ИТК. Поскольку ИТК не уничтожают лейкозные стволовые клетки, остающиеся потенциальным источником рецидива, важную роль при ХМЛ играют естественные киллеры (NK-клетки), обладающие противоопухолевой активностью. Функциональная активность NK-клеток определяется уровнем экспрессии и репертуаром иммуноглобулиноподобных рецепторов киллерных клеток (KIR). Современные исследования свидетельствуют о том, что KIR-генотип пациента оказывает влияние на возможность достижения раннего и глубокого молекулярных ответов на ИТК первого и второго поколений, выживаемость без прогрессирования и общую выживаемость больных, а также сохранение ремиссии без лечения. На этом основании KIR-генетические факторы могут рассматриваться в качестве перспективных предикторов ответа на терапию ИТК у пациентов с ХМЛ. Ранние клинические исследования моноклональных антител, блокирующих ингибирующие KIR с целью повысить активность NK-клеток, показали приемлемые профиль безопасности и эффективность при некоторых гематологических заболеваниях (таких, как острый миелоидный лейкоз, множественная миелома, Т-клеточная лимфома) при использовании в комбинации с цитостатическими препаратами или противоопухолевыми моноклональными антителами. Определение KIR-генотипа при ХМЛ может способствовать разработке эффективных средств иммунотерапии этой злокачественной опухоли системы крови.

Ключевые слова: гены иммуноглобулиноподобных рецепторов киллерных клеток, ингибиторы тирозинкиназ, ремиссия без лечения, хронический миелоидный лейкоз.

Получено: 8 ноября 2022 г.

Принято в печать: 1 марта 2023 г.

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Морфо-иммуногистохимические особенности различных стадий грибовидного микоза: обзор литературы

ОБЗОРЫ , ,

А.А. Шерстнев, А.М. Ковригина

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

Для переписки: Андрей Алексеевич Шерстнев, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; e-mail: sherstnevandrejj@mail.ru

Для цитирования: Шерстнев А.А., Ковригина А.М. Морфо-иммуногистохимические особенности различных стадий грибовидного микоза: обзор литературы. Клиническая онкогематология. 2023;16(2):109–18.

DOI: 10.21320/2500-2139-2023-16-2-109-118

РЕФЕРАТ

Грибовидный микоз (ГМ) — наиболее распространенный вариант Т-клеточной лимфомы кожи. Патогенез ГМ до настоящего времени полностью не изучен. Дифференциальная диагностика заболевания, в особенности на ранних стадиях, сложна и представляет серьезную задачу. В настоящем обзоре литературы освещаются современные представления о патогенезе ГМ и методах диагностики данного заболевания.

Ключевые слова: грибовидный микоз, наивные Т-клетки, Т-хелперы, реактивное микроокружение.

Получено: 21 сентября 2022 г.

Принято в печать: 3 марта 2023 г.

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Хронический гепатит С и онкогематологические заболевания

ОБЗОРЫ , , , ,

Т.В. Антонова1, М.С. Ножкин1, Д.А. Лиознов1,2

1 ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава России, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

2 ФГБУ «НИИ гриппа им. А.А. Смородинцева» Минздрава России, ул. Профессора Попова, д. 15/17, Санкт-Петербург, Российская Федерация, 197376

Для переписки: Тамара Васильевна Антонова, д-р мед. наук, профессор, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; e-mail: antonovatv28@yandex.ru

Для цитирования: Антонова Т.В., Ножкин М.С., Лиознов Д.А. Хронический гепатит С и онкогематологические заболевания. Клиническая онкогематология. 2023;16(1):46–53.

DOI: 10.21320/2500-2139-2023-16-1-46-53

РЕФЕРАТ

В обзоре обсуждается HCV-инфекция у онкогематологических больных. Высокий риск инфицирования вирусом гепатита С (HCV) при онкогематологических заболеваниях доказан значимо большей частотой HCV-инфекции (в 2–2,5 раза) у пациентов с неходжкинскими лимфомами в сравнении с популяционными данными. Кроме того, установлено значение HCV в развитии и прогрессировании В-клеточных неходжкинских лимфом, что подтверждает его онкогенный потенциал. Рассмотрен вариант серонегативного (оккультного) гепатита С, при котором РНК HCV определяется в ткани печени и в мононуклеарах периферической крови высокочувствительным методом ПЦР с обратной транскрипцией при отсутствии антител к HCV и РНК HCV в сыворотке. При этом пациенты могут быть источниками инфекции. Серонегативный гепатит С выявляется у доноров крови в 2,2–3,4 % случаев. Этот вариант инфекции встречается у 20–85 % онкогематологических пациентов, что требует дальнейшего изучения. Сопутствующая HCV-инфекция является потенциальным фактором, влияющим на прогноз онкогематологических заболеваний. У онкогематологических пациентов с сопутствующим хроническим гепатитом С (ХГС) доказана значимо худшая выживаемость в сравнении с больными без него. Установлена связь HCV-инфекции с увеличением частоты осложнений как противоопухолевой терапии, так и трансплантации гемопоэтических стволовых клеток (ТГСК). Иммунохимиотерапия, в свою очередь, влияет на обострение и прогрессирование ХГС. Высокая эффективность и удовлетворительная переносимость препаратов прямого противовирусного действия (ППД) для лечения ХГС открыли перспективы для широкого их использования при наличии сопутствующих заболеваний. Остается сложным вопрос о лечении инфекции у пациентов после ТГСК. Рекомендации по лечению ХГС преимущественно ориентированы на проведение противовирусного лечения до ТГСК. В реальной клинической практике это не всегда возможно. Имеются примеры эффективного применения препаратов ППД до или после ТГСК, описано клиническое наблюдение противовирусного лечения одновременно с ТГСК.

Ключевые слова: вирус гепатита С, HCV-инфекция, онкогематология, трансплантация гемопоэтических стволовых клеток, иммунохимиотерапия, препараты прямого противовирусного действия.

Получено: 17 июня 2022 г.

Принято в печать: 10 декабря 2022 г.

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Комбинация ибрутиниба и венетоклакса в терапии хронического лимфолейкоза: обзор последних данных клинических исследований

ОБЗОРЫ , , , , ,

А.А. Петренко1,2, М.И. Кислова1, Е.А. Дмитриева1, Е.А. Никитин1,2, В.В. Птушкин1,2,3

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

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

3 ФГАОУ ВО «РНИМУ им. Н.И. Пирогова» Минздрава России, ул. Островитянова, д. 1, Москва, Российская Федерация, 117997

Для переписки: Мария Игоревна Кислова, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284; e-mail: xkislovamariax@gmail.com

Для цитирования: Петренко А.А., Кислова М.И., Дмитриева Е.А. и др. Комбинация ибрутиниба и венетоклакса в терапии хронического лимфолейкоза: обзор последних данных клинических исследований. Клиническая онкогематология. 2023;16(1):37–45.

DOI: 10.21320/2500-2139-2023-16-1-37-45

РЕФЕРАТ

Появление ингибиторов тирозинкиназы Брутона (BTK) изменило лечение пациентов с хроническим лимфолейкозом (ХЛЛ). Ибрутиниб, первый в своем классе ингибитор BTK, продемонстрировал высокую эффективность в многочисленных клинических исследованиях. Однако использование ингибиторов BTK в качестве монотерапии требует непрерывного лечения. Резистентность к ингибиторам BTK и тяжелые побочные эффекты неизбежно возникают при монотерапии ибрутинибом, что часто приводит к неэффективности лечения. Комбинация ингибитора BCL-2 венетоклакса с ингибитором BTK может улучшить эффективность терапии за счет синергизма действия препаратов на разные субпопуляции клеток ХЛЛ. Комбинированная терапия может привести к более глубоким ответам, обеспечивая потенциально фиксированную продолжительность лечения. В настоящем обзоре, сосредоточив внимание на комбинации ибрутиниба и венетоклакса, мы обобщаем последние данные клинических исследований, а также отвечаем на вопрос, касающийся обоснованности комбинированной терапии с точки зрения ее эффективности и профиля безопасности.

Ключевые слова: ибрутиниб, ингибиторы BTK, венетоклакс, ингибиторы BCL-2, таргетные препараты, хронический лимфолейкоз.

Получено: 17 октября 2022 г.

Принято в печать: 10 ноября 2022 г.

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Прогностические модели в медицине

ОБЗОРЫ ,

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. Прогностические модели в медицине. Клиническая онкогематология. 2023;16(1):27–36.

DOI: 10.21320/2500-2139-2023-16-1-27-36

РЕФЕРАТ

Медицинские прогностические (предиктивные) модели (МПМ) имеют важное значение в современном здравоохранении. Они определяют риски для здоровья и возникновения заболеваний. Целью их создания является улучшение результатов диагностики и лечения. Все МПМ можно разделить на две категории. Диагностические медицинские модели (ДММ) помогают рассчитать индивидуальный риск присутствия заболевания, в то время как прогностические медицинские модели (ПММ) — риск возникновения болезни или его осложнения в будущем. В обзоре обсуждаются характеристики ДММ и ПММ, условия их разработки, критерии применения в медицине, в частности в гематологии, а также проблемы, возникающие на этапе их создания и проверки качества.

Ключевые слова: прогностическая модель, искусственный интеллект.

Получено: 13 сентября 2022 г.

Принято в печать: 7 декабря 2022 г.

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Острые миелоидные лейкозы после лечения классической лимфомы Ходжкина: обзор литературы

ОБЗОРЫ

А.А. Даниленко, С.В. Шахтарина, Н.А. Фалалеева

Медицинский радиологический научный центр им. А.Ф. Цыба — филиал ФГБУ «НМИЦ радиологии» Минздрава России, ул. Королева, д. 4, Обнинск, Калужская область, Российская Федерация, 249036

Для переписки: Анатолий Александрович Даниленко, д-р мед. наук, ул. Королева, д. 4, Обнинск, Калужская область, Российская Федерация, 249036; тел.: +7(909)250-18-10; e-mail: danilenkoanatol@mail.ru

Для цитирования: Даниленко А.А., Шахтарина С.В., Фалалеева Н.А. Острые миелоидные лейкозы после лечения классической лимфомы Ходжкина: обзор литературы. Клиническая онкогематология. 2022;15(4):414–23.

DOI: 10.21320/2500-2139-2022-15-4-414-423

РЕФЕРАТ

Вторые злокачественные опухоли, развивающиеся у больных классической лимфомой Ходжкина (кЛХ) после лечения, представлены преимущественно солидными новообразованиями и в значительно меньшей степени острыми миелоидными лейкозами (ОМЛ). Вместе с тем относительный риск развития вторичного ОМЛ существенно превышает риск развития вторых (солидных) опухолей, а эффективность лечения больных вторичным ОМЛ значительно уступает результатам лечения первичного ОМЛ, что делает проблему значимой и актуальной. Настоящий обзор литературы посвящен эпидемиологии развития вторичных ОМЛ у больных, получавших лечение по поводу кЛХ. Кроме того, уделяется внимание современным лекарственным препаратам и технологиям, эффективным в отношении вторичных ОМЛ.

Ключевые слова: классическая лимфома Ходжкина, вторичные острые миелоидные лейкозы.

Получено: 15 апреля 2022 г.

Принято в печать: 28 августа 2022 г.

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Статистика Plumx русский

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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

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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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