ОБЗОРЫ

Актуальные вопросы таргетной терапии истинной полицитемии

ОБЗОРЫ , , ,

А.Л. Меликян, И.Н. Суборцева

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

Для переписки: Анаит Левоновна Меликян, д-р мед. наук, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; e-mail: anoblood@ mail.ru

Для цитирования: Меликян А.Л., Суборцева И.Н. Актуальные вопросы таргетной терапии истинной полицитемии. Клиническая онкогематология. 2021;14(3):355–60.

DOI: 10.21320/2500-2139-2021-14-3-355-360

РЕФЕРАТ

Вопросы использования критериев ответа на терапию, непереносимости гидроксикарбамида в первой линии, резистентности к нему и раннего изменения тактики лечения остаются спорными и не до конца решенными у пациентов с истинной полицитемией. В обзоре представлены результаты анализа данных литературы в отношении оценки эффективности первой линии терапии, проанализированы спектр и частота нежелательных явлений при применении гидроксикарбамида, опыт использования ингибитора JAK2 руксолитиниба. Приведены результаты, в т. ч. отдаленные, сравнительного анализа использования руксолитиниба и наилучшей доступной терапии у больных истинной полицитемией с резистентностью к гидроксикарбамиду. В настоящем обзоре использован материал работы экспертного совета с профессором Джузеппе А. Палумбо (университет Катании, Сицилия, Италия), который состоялся 7 июня 2020 г.

Ключевые слова: истинная полицитемия, JAK2V617F, прогноз, гидроксикарбамид, руксолитиниб.

Получено: 22 декабря 2020 г.

Принято в печать: 10 мая 2021 г.

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ЛИТЕРАТУРА

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CAR Т-клетки для лечения хронического лимфоцитарного лейкоза: обзор литературы

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. CAR Т-клетки для лечения хронического лимфоцитарного лейкоза: обзор литературы. Клиническая онкогематология. 2021;14(2):225–30.

DOI: 10.21320/2500-2139-2021-14-2-225-230

РЕФЕРАТ

Хронический лимфоцитарный лейкоз (ХЛЛ) является наиболее распространенным злокачественным лимфоидным заболеванием взрослых. Несмотря на появление новых высокоэффективных таргетных препаратов, прогноз у больных с рецидивами и резистентной формой заболевания остается неблагоприятным. CAR Т-клеточная терапия, предполагающая использование Т-лимфоцитов с химерным антигенным рецептором (CAR), продемонстрировала свою эффективность в лечении ряда онкогематологических заболеваний, таких как В-клеточные неходжкинские лимфомы и острый лимфобластный лейкоз. В настоящем обзоре литературы рассматривается опыт применения CAR Т-клеток для лечения ХЛЛ. Представлены преимущества и недостатки данной технологии, а также проблемы, которые еще предстоит решить для внедрения метода в широкую клиническую практику.

Ключевые слова: хронический лимфоцитарный лейкоз, CAR T-клеточная терапия, химерный антигенный рецептор, адоптивная терапия, иммунотерапия.

Получено: 15 декабря 2020 г.

Принято в печать: 10 марта 2021 г.

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ЛИТЕРАТУРА

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COVID-19 у пациентов с онкогематологическими заболеваниями

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. COVID-19 у пациентов с онкогематологическими заболеваниями. Клиническая онкогематология. 2021;14(2):220–4.

DOI: 10.21320/2500-2139-2021-14-2-220-224

РЕФЕРАТ

Эпидемия COVID-19, разразившаяся в Ухане (Китай), быстро переросла в пандемию. Высокая смертность от этого заболевания ставит его в ряд наиболее опасных вирусных инфекционных болезней настоящего времени. В то время как наибольшему риску летального исхода подвержены лица пожилого возраста, некоторые сопутствующие заболевания, среди которых вполне могут быть и злокачественные опухоли, также существенно ухудшают течение COVID-19. В силу присущего иммунодефицита, усугубляемого иммуносупрессивной противоопухолевой терапией, ведущее место по влиянию на течение COVID-19 занимают онкогематологические заболевания. В обзоре представлены немногочисленные опубликованные сведения о влиянии коронавирусной инфекции на прогноз у пациентов с опухолями кроветворной и лимфоидной тканей. Кроме того, обсуждаются возможные меры по снижению у этих больных риска летального исхода.

Ключевые слова: SARS-CoV-2, COVID-19, онкогематологические заболевания, смертность.

Получено: 13 октября 2020 г.

Принято в печать: 15 февраля 2021 г.

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ЛИТЕРАТУРА

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Биотехнология CAR-T и новые возможности лечения опухолевых заболеваний

ОБЗОРЫ ,

В.Ю. Павлова1, Е.С. Ливадный2

1 ГАУЗ «Кемеровская областная клиническая больница им. С.В. Беляева», Октябрьский пр-т, д. 22, корп. 2, Кемерово, Российская Федерация, 650066

2 ФГБОУ ВО «Кемеровский государственный медицинский университет», ул. Ворошилова, д. 22а, Кемерово, Российская Федерация, 650056

Для переписки: Вера Юрьевна Павлова, канд. мед. наук, Октябрьский пр-т, д. 22, корп. 2, Кемерово, Российская Федерация, 650066; тел.: +7(951)570-57-86; e-mail: vera.4447.kem@mail.ru

Для цитирования: Павлова В.Ю., Ливадный Е.С. Биотехнология CAR-T и новые возможности лечения опухолевых заболеваний. Клиническая онкогематология. 2021;14(1):149–56.

DOI: 10.21320/2500-2139-2021-14-1-149-156

РЕФЕРАТ

Злокачественные новообразования как причина смерти занимают 2-е место в мире после сердечно-сосудистых заболеваний. CAR T-терапия (chimeric antigen receptor of T-cells) — прогрессивный метод лечения злокачественных опухолей. Использование CAR Т-лимфоцитов относится к адоптивной иммунотерапии. Технология CAR-T основана на «извлечении» клеток иммунной системы (Т-лимфоцитов) из организма, их генетической модификации в целях приобретения ими противоопухолевых свойств с последующей реинфузией пациенту. Преимущество CAR T-терапии в сравнении с другими методами лечения заключается в том, что для распознавания клеток-мишеней Т-лимфоциты не нуждаются в присутствии молекул главного комплекса гистосовместимости 1-го класса (MHC-I). Собранные и проанализированные нами литературные данные свидетельствуют о появлении принципиально нового эффективного метода лечения онкогематологических заболеваний, включая острый лимфобластный лейкоз, хронический лимфолейкоз и неходжкинские лимфомы. На основании клинических исследований доказано преимущество CAR T-терапии в сравнении с другими методами лечения, применяющимися в данной области. Анализ литературы позволил сделать вывод об обоснованности рассмотрения CAR T-терапии как одной из перспективных возможностей воздействия на злокачественную опухоль.

Ключевые слова: адоптивная иммунотерапия, CAR T-лимфоциты, химерный антигенный рецептор.

Получено: 20 сентября 2020 г.

Принято в печать: 1 декабря 2020 г.

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Клеточный препарат с химерным антигенным рецептором NKG2D в CAR T-терапии рецидивов/рефрактерных острых миелоидных лейкозов и миелодиспластического синдрома

ОБЗОРЫ , , ,

К.A. Левчук1, Е.В. Белоцерковская1,2, Д.Ю. Поздняков1, Л.Л. Гиршова1, А.Ю. Зарицкий1, А.В. Петухов1,2,3

1 ФГБУ «НМИЦ им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341

2 ФГБУН «Институт цитологии РАН», Тихорецкий пр-т, д. 4, Санкт-Петербург, Российская Федерация, 194064

3 НТУ «Сириус», Олимпийский пр-т, д. 1, Сочи, Российская Федерация, 354340

Для переписки: Ксения Александровна Левчук, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341; e-mail: levchuk_ka@almazovcentre.ru

Для цитирования: Левчук К.A., Белоцерковская Е.В., Поздняков Д.Ю. и др. Клеточный препарат с химерным антигенным рецептором NKG2D в CAR T-терапии рецидивов/рефрактерных острых миелоидных лейкозов и миелодиспластического синдрома. Клиническая онкогематология. 2021;14(1):138–48.

DOI: 10.21320/2500-2139-2021-14-1-138-148 

РЕФЕРАТ

NK-клетки как элементы врожденного иммунитета реализуют ключевые реакции противоопухолевого иммунного ответа. NKG2D — активационный трансмембранный рецептор NK-клеток, ответственный за инициацию цитотоксичности в ответ на связывание специфичных лигандов генетически модифицированных клеток. Селективная экспрессия лигандов NKG2D открывает уникальные перспективы для терапии широкого спектра опухолей. Острые миелоидные лейкозы (ОМЛ) — это злокачественные опухоли системы крови, характеризующиеся высоким риском развития рецидивов. Сложность терапевтической стратегии при ОМЛ создает необходимость поиска новых подходов к элиминации опухоли с применением инновационных генетических конструкций. Имеющиеся к настоящему времени CAR T-клеточные препараты, несущие рецептор NKG2D, успешно изучаются в клинических исследованиях у пациентов с ОМЛ, доказывая свой высокий терапевтический потенциал.

Ключевые слова: острые миелоидные лейкозы, химерный антигенный рецептор, адоптивная терапия, NKG2D, NK-клетки.

Получено: 22 августа 2020 г.

Принято в печать: 5 декабря 2020 г.

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Статистика Plumx русский

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Современный взгляд на диагностику и лечение классических Ph-негативных миелопролиферативных заболеваний

ОБЗОРЫ , , , , , , , ,

А.Л. Меликян1, И.Н. Суборцева1, В.А. Шуваев2,3, Е.Г. Ломаиа4, Е.В. Морозова5, Л.А. Кузьмина1, О.Ю. Виноградова6,7,8, А.Ю. Зарицкий4

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

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

3 ГБУЗ » Городская клиническая больница им. В.В. Вересаева» ДЗМ, ул. Лобненская, д. 10, Москва, Российская Федерация, 127644

4 ФГБУ «НМИЦ им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341

5 НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, 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

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

7 ФГБУ «НМИЦ детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России, ул. Саморы Машела, д. 1, Москва, Российская Федерация, 117997

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

Для переписки: Анаит Левоновна Меликян, д-р мед. наук, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; e-mail: anoblood@mail.ru

Для цитирования: Меликян А.Л., Суборцева И.Н., Шуваев В.А. и др. Современный взгляд на диагностику и лечение классических Ph-негативных миелопролиферативных заболеваний. Клиническая онкогематология. 2021;14(1):129–37.

DOI: 10.21320/2500-2139-2021-14-1-129-137

РЕФЕРАТ

Классические Ph-негативные миелопролиферативные заболевания (МПЗ) — группа опухолей, включающая в себя истинную полицитемию, эссенциальную тромбоцитемию и первичный миелофиброз. В последнее десятилетие существенно изменились подходы к пониманию патогенеза и лечению МПЗ. В то же время продолжается тщательное изучение этиологических факторов, патофизиологических механизмов развития заболевания. Совершенствование методов диагностики, новые подходы к лечению способны снизить риски осложнений и летальных исходов. В обзоре представлены современные методы диагностики, в т. ч. молекулярно-генетический, приведены прогностические шкалы. Кроме того, оцениваются различные методы консервативного лечения. Особое внимание уделено оценке качества жизни пациентов и таргетному лечению заболеваний.

Ключевые слова: миелопролиферативные заболевания, истинная полицитемия, эссенциальная тромбоцитемия, первичный миелофиброз, JAK2V617F, CALR, MPL, прогноз, конституциональные симптомы, MPN10, руксолитиниб.

Получено: 1 сентября 2020 г.

Принято в печать: 10 декабря 2020 г.

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ЛИТЕРАТУРА

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Возможности терапии ингибиторами тирозинкиназ в сниженных дозах у пациентов с хроническим миелолейкозом

ОБЗОРЫ , , , ,

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

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

Для переписки: Маргарита Анатольевна Гурьянова, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; тел.: +7(985)201-70-40; e-mail: margarita.samtcova@yandex.ru

Для цитирования: Гурьянова М.А., Челышева Е.Ю., Туркина А.Г. Возможности терапии ингибиторами тирозинкиназ в сниженных дозах у пациентов с хроническим миелолейкозом. Клиническая онкогематология. 2021;14(1):118–28.

DOI: 10.21320/2500-2139-2021-14-1-118-128

РЕФЕРАТ

Терапия ингибиторами тирозинкиназ (ИТК) у 60–70 % больных хроническим миелоидным лейкозом (ХМЛ) позволяет получить глубокий молекулярный ответ (МО). Однако, несмотря на высокую эффективность ИТК, у многих пациентов лечение сопровождается проявлениями лекарственной токсичности. По результатам клинических исследований вероятность сохранения ремиссии без лечения у больных ХМЛ с глубоким МО составляет примерно 40–60 %. В последнее время большое внимание уделяется персонализированному подходу к терапии при ХМЛ в хронической фазе. Он заключается в модификации дозы ИТК с целью уменьшить или предотвратить развитие нежелательных явлений. В рамках крупных ретроспективных исследований было доказано, что терапия сниженными дозами ИТК у больных с оптимальным ответом является безопасной с точки зрения сохранения достигнутого большого МО и глубокого МО при стандартных дозах ИТК. Наблюдение за пациентом при применении сниженных доз ИТК также рассматривается в рамках проспективных клинических исследований как этап перед отменой терапии. Тем не менее к настоящему времени опубликованы результаты всего 4 подобных исследований. Для подробного изучения вопросов, касающихся длительного наблюдения за больными ХМЛ при использовании сниженных доз ИТК, необходимо проведение проспективных клинических исследований. В настоящем обзоре представлены результаты основных исследований по ведению больных ХМЛ, получающих ИТК в сниженных дозах.

Ключевые слова: хронический миелоидный лейкоз, ингибиторы тирозинкиназ, большой молекулярный ответ, глубокий молекулярный ответ, нежелательные явления, фармакокинетика ингибиторов тирозинкиназ.

Получено: 3 августа 2020 г.

Принято в печать: 20 ноября 2020 г.

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ЛИТЕРАТУРА

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EVI1 -позитивные лейкозы и миелодиспластические синдромы: теоретические и клинические аспекты (обзор литературы)

ОБЗОРЫ , , , , ,

Н.Н. Мамаев, А.И. Шакирова, Е.В. Морозова, Т.Л. Гиндина

НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, 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: Николай Николаевич Мамаев, д-р мед. наук, профессор, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; e-mail: nikmamaev524@gmail.com

Для цитирования: Мамаев Н.Н., Шакирова А.И., Морозова Е.В., Гиндина Т.Л. EVI1-позитивные лейкозы и миелодиспластические синдромы: теоретические и клинические аспекты (обзор литературы). Клиническая онкогематология. 2021;14(1):103–17.

DOI: 10.21320/2500-2139-2021-14-1-103-117

РЕФЕРАТ

Настоящий обзор посвящен анализу теоретической базы и проводимой в клинике НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой терапии наиболее неблагоприятных в прогностическом отношении EVI1-позитивных вариантов миелоидных лейкозов и миелодиспластических синдромов. Основной акцент в работе сделан на доказательстве ведущей роли гена EVI1 в нарушении эпигенетической регуляции гемопоэза и, следовательно, целесообразности использования трансплантации аллогенных гемопоэтических стволовых клеток с гипометилирующими агентами и/или транс-ретиноевой кислотой для лечения этих заболеваний.

Ключевые слова: EVI1, острые миелоидные лейкозы, хронический миелоидный лейкоз, миелодиспластический синдром, аллоТГСК, гипометилирующие агенты, транс-ретиноевая кислота.

Получено: 12 сентября 2020 г.

Принято в печать: 6 декабря 2020 г.

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Мантийноклеточная лимфома: история, современные принципы диагностики, лечение (обзор литературы)

ОБЗОРЫ

Г.С. Тумян

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

Для переписки: Гаяне Сепуговна Тумян, д-р мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; e-mail: gaytum@mail.ru

Для цитирования: Тумян Г.С. Мантийноклеточная лимфома: история, современные принципы диагностики, лечение (обзор литературы). Клиническая онкогематология. 2020;13(4):366–81.

DOI: 10.21320/2500-2139-2020-13-4-366-381

РЕФЕРАТ

Мантийноклеточная лимфома (МКЛ) — гетерогенное заболевание с широким спектром клинических проявлений от редких индолентных случаев, не требующих немедленного начала терапии, до агрессивных, быстро пролиферирующих типов опухоли. Разное клиническое поведение имеет молекулярное обоснование, которое позволило в последней редакции классификации опухолей кроветворной и лимфоидной тканей ВОЗ разделить МКЛ на два варианта: классический (в большинстве случаев) и индолентный. Последние десятилетия расширили наши представления о биологии и механизмах развития заболевания. Это делает возможным в дальнейшем стратифицировать больных на разные группы риска не только в зависимости от клинических факторов (MIPI), но и с учетом молекулярных и биологических особенностей опухоли (индекс пролиферации Ki-67, мутации генов ТР53, NOTCH1, NOTCH2, комплексный кариотип, немутантный статус IGHV). Алгоритмы лечения, основанные на интенсивной химиотерапии с включением цитарабина в высоких дозах, трансплантации аутологичных гемопоэтических стволовых клеток с дальнейшей поддерживающей терапией ритуксимабом, позволили длительно контролировать заболевание у значительного числа больных МКЛ. Применение новых «chemo-free» режимов и рациональных комбинаций (бортезомиб, ингибиторы BTK, леналидомид, венетоклакс) вселяет надежду на возможность ухода от традиционной химиотерапии у определенной части пациентов. Появление новых лекарственных средств с уникальными механизмами действия позволили в какой-то степени снять «печать фатальности» с МКЛ.

Ключевые слова: мантийноклеточная лимфома, лечение.

Получено: 17 июня 2020 г.

Принято в печать: 2 сентября 2020 г.

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Пироптоз — воспалительная форма клеточной гибели

ОБЗОРЫ , , ,

А.А. Вартанян, В.С. Косоруков

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

Для переписки: Aмалия Арташевна Вартанян, д-р биол. наук, ул. Каширская, д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-10-65; e-mail: zhivotov57@mail.ru

Для цитирования: Вартанян А.А., Косоруков В.С. Пироптоз — воспалительная форма клеточной гибели. Клиническая онкогематология. 2020;13(2):129–35.

DOI: 10.21320/2500-2139-2020-13-2-129-135

РЕФЕРАТ

Пироптоз, каспаза-1-зависимая воспалительная форма гибели клетки, индуцируется внутриклеточными патогенами или повреждением тканей. Активация прокаспазы-1, необходимая для процессинга провоспалительных цитокинов про-IL-1β и про-IL-18, происходит в макромолекулярных белковых комплексах, называемых инфламмасомами. При инфекциях, вызванных грамотрицательными бактериями, в сборке инфламмасомы участвует каспаза-4 и каспаза-5. Первоначально идентифицированный как защитный механизм врожденного иммунитета, пироптоз сегодня не ограничивается ингибированием размножения внутриклеточных патогенов. В данном обзоре обсуждаются молекулярные механизмы гибели клетки по типу пироптоза и возможности вовлечения пироптоза в гибель опухолевых клеток.

Ключевые слова: клеточная гибель, пироптоз, каспазы, воспаление, врожденный иммунитет.

Получено: 24 декабря 2019 г.

Принято в печать: 17 марта 2020 г.

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