лечение

Оптимизация диагностики и лечения лимфомы Беркитта у детей, подростков и молодых взрослых

КЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ЛИМФОИДНЫХ ОПУХОЛЕЙ , , , , , ,

Т.Т. Валиев1, Е.А. Барях2, П.А. Зейналова3, А.М. Ковригина2, С.К. Кравченко2, Т.Н. Обухова2, Н.А. Фалалеева3, А.И. Сендерович3, И.Н. Серебрякова3, И.В. Каминская1, А.C. Левашов1, Г.Л. Менткевич1

1 НИИ детской онкологии и гематологии ФГБУ «РОНЦ им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

2 ФГБУ «Гематологический научный центр» МЗ РФ, Москва, Российская Федерация

3 НИИ клинической онкологии ФГБУ «РОНЦ им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

В работе представлен и обобщен опыт ведущих российских онкогематологических клиник. В статье приводятся иммуноморфологические и цитогенетические критерии диагностики лимфомы Беркитта (ЛБ) у детей, подростков и молодых взрослых. Описаны клинические особенности ЛБ в разных возрастных группах. Освещены вопросы лечения ЛБ по современным программами B-NHL-BFM 90/95 и CODOX-M/IVAC. Приводятся результаты лечения по оригинальному отечественному протоколу ЛБ-М-04. Обсуждается место ритуксимаба в терапии ЛБ.

Ключевые слова: лимфома Беркитта, дети, подростки, молодые взрослые, клиника, диагностика, лечение

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Множественная миелома (лечение рецидивов и рефрактерных форм): обзор литературы и собственные данные. Часть III

КЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ЛИМФОИДНЫХ ОПУХОЛЕЙ , , , , , , , , , , ,

С.С. Бессмельцев

ФГБУ «Российский научно-исследовательский институт гематологии и трансфузиологии Федерального медико-биологического агентства», Санкт-Петербург, Российская Федерация

РЕФЕРАТ

Использование новых подходов в лечении рецидивов/рефрактерных форм множественной миеломы (ММ) привело к существенному увеличению общей выживаемости больных, достижению качественного ответа и более длительной ремиссии по сравнению с пациентами, получавшими стандартную химиотерапию. Эти изменения связаны главным образом с применением новых препаратов: бортезомиба, талидомида, леналидомида, каждый из которых обладает выраженной противомиеломной активностью. Бортезомиб, талидомид и леналидомид используются в комбинации как с химиотерапевтическими препаратами, так и друг с другом, что существенно повышает эффективность лечения больных ММ. Однако, если больные не отвечают на бортезомиб и иммуномодуляторы, прогноз ухудшается. В настоящее время число препаратов, которые используются при ММ, достаточно большое, причем спектр их все более расширяется. Тем не менее результаты лечения больных с рецидивами/рефрактерными формами ММ не вполне удовлетворительные, что свидетельствует о трудностях разработки эффективных лекарственных средств. Появилось большое количество препаратов второго и третьего поколений, которые становятся все более доступными для клинического применения. Проводятся клинические исследования I, II и III фаз по оценке эффективности карфилзомиба, помалидомида, вориностата, панобиностата, ромидепсина, перифосина, танеспимицина, бендамустина и элотузумаба при рецидивах/рефрактерных формах ММ. В обзоре представлены современные подходы к ведению пациентов с рецидивами и рефрактерным течением ММ, основанные на результатах клинических исследований и собственных данных, целью которых было оптимизировать результаты лечения. Представлена эффективность различных классов новых лекарственных средств, обсуждены все «за» и «против», полученные в доклинических и клинических исследованиях. Подробно освещены побочные эффекты новых препаратов.

Ключевые слова: множественная миелома, рецидив, рефрактерное течение, бортезомиб, талидомид, леналидомид, карфилзомиб, помалидомид, лечение, полная ремиссия, общая выживаемость, нейропатия.

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Множественная миелома (лечение первичных больных): обзор литературы и собственные данные. Часть II

КЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ЛИМФОИДНЫХ ОПУХОЛЕЙ , , , , , , , ,

С.С. Бессмельцев

ФГБУ «Российский научно-исследовательский институт гематологии и трансфузиологии Федерального медико-биологического агентства», Санкт-Петербург, Российская Федерация

РЕФЕРАТ

В последние десятилетия в результате широкого применения аутологичной трансплантации гемопоэтических стволовых клеток (аутоТГСК) и новых, весьма эффективных лекарственных средств существенно улучшились показатели выживаемости пациентов с множественной миеломой (ММ) в возрасте до 65 лет (молодые пациенты). У пациентов с ММ в возрасте старше 65 лет традиционно используется комбинация мелфалана и преднизолона (MP). Внедрение новых препаратов, в частности иммуномодулирующих средств (ИМС) и ингибиторов протеасомы, значительно изменило подходы к лечению этого заболевания. У больных с впервые выявленной ММ была изучена эффективность многих двух-, трех- и четырехкомпонентных комбинаций. Установлено, что достижение полной ремиссии (ПР) служит независимым предиктором длительной выживаемости (ВБП, ОВ). Результаты проведенных проспективных исследований свидетельствуют о том, что для достижения высокого значения ПР и увеличения ее продолжительности необходимо индукционное лечение с использованием трехкомпонентных режимов, содержащих бортезомиб или иммуномодуляторы, с последующей аутоТГСК, консолидацией/поддерживающей терапией ИМС или ингибиторами протеасомы. В преобладающем большинстве случаев пожилые пациенты не являются кандидатами на аутоТГСК. Внедрение в лечебную практику новых препаратов — талидомида, бортезомиба, леналидомида — значительно улучшило результаты лечения этих больных. Программы MP + талидомид (MPT), MP + бортезомиб (VMP) и MP + леналидомид с последующей поддерживающей терапией леналидомидом (MPR-R) в настоящее время рассматриваются в качестве новых стандартов лечения пожилых пациентов с ММ. Прогноз ММ зависит от множества факторов, которые следует учитывать до начала терапии. В обзоре представлены современные подходы к ведению пациентов с впервые выявленной ММ, основанные на проводимых в настоящее время исследованиях, цель которых заключается в оптимизации результатов лечения.

Ключевые слова: множественная миелома, бортезомиб, талидомид, леналидомид, лечение, полная ремиссия, общая выживаемость, нейропатия, аутологичная трансплантация гемопоэтических стволовых клеток.

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Саркома из интердигитирующих дендритных клеток: клиническое наблюдение и данные литературы

РЕДКИЕ ГЕМАТОЛОГИЧЕСКИЕ ЗАБОЛЕВАНИЯ И СИНДРОМЫ , ,

П.А. Зейналова1, А.И. Павловская1, Т.Т. Валиев2, Н.В. Кокосадзе1

1 НИИ клинической онкологии ФГБУ «РОНЦ им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

2 НИИ детской онкологии ФГБУ «РОНЦ им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

Представлены литературные данные и описание собственного клинического наблюдения крайне редкой опухоли, принадлежащей к опухолям из гистиоцитарных и дендритных клеток, — саркомы из интердигитирующих дендритных клеток (СИДК). Разнообразная клиническая картина с поражением нодальных и экстранодальных зон, а также иммуноморфологические особенности этой саркомы заставляют проводить дифференциальный диагноз с целым рядом опухолей, в первую очередь с саркомой из фолликулярных дендритных клеток, лангергансоклеточным гистиоцитозом, меланомой, неходжкинскими лимфомами. Приводится описание клинического наблюдения СИДК с поражением лимфоузла шеи. Лечение (СНОР с последующей лучевой терапией) было успешным. Тактика лечения СИДК не разработана. Используются хирургический, лучевой и медикаментозный методы противоопухолевого воздействия.

Ключевые слова: саркома из интердигитирующих дендритных клеток, диагностика, лечение.

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ЛИТЕРАТУРА

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Современные методы лечения AL амилоидоза: обзор литературы и собственные данные

КЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ЛИМФОИДНЫХ ОПУХОЛЕЙ , , , ,

А.Г. Смирнова1, С.Н. Бондаренко1, А.А. Кисина2, А.В. Смирнов2, А. Цандер3, Б.В. Афанасьев1

1 Институт детской гематологии, онкологии и трансплантологии им. Р.М. Горбачевой СПбГМУ им. акад. И.П. Павлова, Санкт-Петербург, Российская Федерация

2 Научно-исследовательский институт нефрологии СПбГМУ им. акад. И.П. Павлова, Санкт-Петербург, Российская Федерация

3 Центр трансплантации костного мозга Медицинского университета Гамбург-Эппендорф, Гамбург, Германия

РЕФЕРАТ

AL амилоидоз — достаточно редкое заболевание из группы плазмоклеточных дискразий, имеющее крайне неоднородную клиническую картину и плохой прогноз. В статье представлено краткое описание данной патологии, проведен обзор современных методов лечения, представлены собственные результаты терапии. В исследование включено 46 больных с диагнозом AL амилоидоза, которые получали лечение как с использованием аутологичной трансплантации гемопоэтических стволовых клеток, так и стандартной химиотерапии, включающей комбинацию мелфалана с дексаметазоном и бортезомиба с дексаметазоном.

Ключевые слова: AL амилоидоз, лечение, трансплантация гемопоэтических стволовых клеток, мелфалан, бортезомиб.

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Мантийноклеточная лимфома: программное лечение первичных больных в возрасте до 65 лет

КЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ЛИМФОИДНЫХ ОПУХОЛЕЙ , , ,

В.И. Воробьев1, С.К. Кравченко1, Э.Г. Гемджян1, Ю.Ю. Лорие2, А.У. Магомедова1, А.Л. Меликян1, Я.К. Мангасарова1, Д.С. Марьин1, Е.И. Дубровин1, Т.Н. Обухова1, С.А. Махиня1, В.А. Жеребцова3, М.А. Вернюк4, Н.Г. Тюрина4, В.Г. Савченко1

1 ФГБУ «Гематологический научный центр» МЗ РФ, Москва, Российская Федерация

2 Московский онкологический диспансер № 3, Российская Федерация

3 ФГБУ «Центральная клиническая больница с поликлиникой Управления делами президента РФ», Москва, Российская Федерация

4 МНИОИ им. П.А. Герцена, Москва, Российская Федерация

РЕФЕРАТ

Введение. Лимфома из клеток мантийной зоны (ЛКМЗ) — это агрессивная В-клеточная опухоль, которая диагностируется преимущественно у мужчин старшей возрастной группы. Использование высоких доз цитарабина (12 г/м2 на курс; J. Romanguera, 2005), аутологичной трансплантации гемопоэтических стволовых клеток (аутоТГСК)и ритуксимаба на всех этапах терапии является наиболее эффективным лечебным подходом у пациентов моложе 65 лет. Уменьшение дозы цитарабина до 4 г/м2 на курс значительно ухудшает показатели выживаемости без прогрессирования. Высокая эффективность гемцитабин/оксалиплатин-содержащих режимов и иринотекана в лечении рецидивов ЛКМЗ допускает их использование в первой линии терапии.

Цель. Оценить эффективность и токсичность схем терапии R-EPOCH/R-GIDIOX и R-EPOCH/R-HD-Met-AraC у первичных пациентов с ЛКМЗ, рекрутируемых для выполнения аутоТГСК.

Пациенты и методы. С мая 2008 г. в исследование включен 41 пациент с цитогенетически доказанной ЛКМЗ. Медиана возраста 54 года (диапазон 29–64 года), мужчин — 73 %, женщин — 27 %. MIPIb: 29,3 % — низкого, 36,6 % — промежуточного и 34,1 % — высокого риска. После первого курса по схеме R-EPOCH (W. Wilson, 2003) в зависимости от развившейся токсичности пациенты были разделены на две группы. При отсутствии гематологической токсичности IV степени более 3 дней, серьезных инфекционных осложнений или признаков почечной недостаточности пациентам в дальнейшем проводилась терапия по схеме R-HD-Met-AraC (ритуксимаб 375 мг/м2 в 0-й день, метотрексат 1000 мг/м2 в течение 24 ч в 1-й день, цитарабин 3000 мг/м2 2 раза в сутки во 2–3-й день). При развитии одного из перечисленных выше осложнений пациентам после первого курса R-EPOCH проводился курс полихимиотерапии (ПХТ) по схеме R-GIDIOX (ритуксимаб 375 мг/м2 в 0-й день, гемцитабин 800 мг/м2 в 1-й и 4-й дни, оксалиплатин 120 мг/м2 во 2-й день, иринотекан 100 мг/м2 в 3-й день, дексаметазон 10 мг/м2 в/в в 1–5-й день, ифосфамид 1000 мг/м2 в 1–5-й день). В дальнейшем данные курсы ПХТ чередовались: пациенты получали лечение по схеме R-EPOCH/R-HD-Met-AraC или R-EPOCH/R-GIDIOX соответственно. В зависимости от времени достижения полной ремиссии (ПР) проводилось 6–8 курсов терапии и выполнялась аутоТГСК (BEAM-R). С целью «очистки» непосредственно перед сбором гемопоэтических стволовых клеток и перед аутоТГСК вводили ритуксимаб в дозе 375 мг/м2. Пациентам с резидуальной опухолью после аутоТГСК проводилась локальная лучевая терапия, в дальнейшем — поддерживающая терапия ритуксимабом в дозе 375 мг/м2 1 раз в 3 мес. в течение 3 лет. Протокол одобрен местным этическим комитетом. Оценка бессобытийной и общей выживаемости проводилась от момента начала терапии. Эффективность терапии оценивалась согласно критериям B. Cheson (2007). С ноября 2011 г. всем пациентам проводится профилактика нейролейкоза (включая больных, которым аутоТГСК была выполнена после ноября 2010 г.). Проанализирована токсичность 124 курсов R-EPOCH, 87 курсов R-HD-Met-AraC и 51 курса R-GIDIOX.

Результаты. Медиана наблюдения составила 22 мес. (диапазон 4–60 мес.). К апрелю 2013 г. 35 пациентам выполнена аутоТГСК: 21 — из группы R-HD-Met-AraC и 14 — из группы R-GIDIOX. Вследствие развития острой почечной недостаточности и септического шока 1 больной умер на этапе индукции после первого курса по схеме R-HD-Met-AraC. Поддерживающая терапия ритуксимабом завершена у 5 больных. У всех пациентов, получивших высокодозную индукцию по схеме R-EPOCH/R-HD-Met-AraC, достигнута ПР заболевания. В группе R-EPOCH/R-GIIDOX противоопухолевый ответ достигнут в 93 % случаев: ПР — у 12 из 15 пациентов, ЧР — у 2 из 15, прогрессирование заболевания — у 1 из 15. Основной негематологической токсичностью курсов R-GIDIOX стала печеночная недостаточность; повышение активности аминотрансфераз до I–II и III–IV степени наблюдалось в 64,7 и 7,8 % случаев соответственно, но без клинических проявлений. У 27 из 31 больного использованы стволовые клетки периферической крови, в 4 случаях выполнены эксфузии костного мозга. Гематологическая токсичность курсов R-GIDIOX: лейкопения IV степени — 74,5 % случаев (медиана продолжительности 5 дней, диапазон 1–13 дней), тромбоцитопения IV степени — 39,2 %. Ожидаемая 5-летняя общая выживаемость в группах R-GIDIOX и R-HD-Met-AraC составила 93 ± 7 и 79 % ± 12 % соответственно; бессобытийная выживаемость — 59 % ± 19 и 74 % ± 12 % соответственно.

Заключение. Схема R-HD-Met-AraC высокотоксична, и ее использование возможно только у 2/3 пациентов моложе 65 лет. Схема ПХТ R-GIDIOX менее токсична, чем R-HD-Met-AraC, а ее эффективность сравнима по частоте достижения ПР и мобилизации необходимого количества аутоГСК. Это позволяет рекомендовать применение гемцитабин/оксалиплатин-содержащих режимов в тех случаях, когда использование высоких доз метотрексата и цитарабина сопряжено с высоким риском угрожающих жизни осложнений.

Ключевые слова: лимфома из клеток мантийной зоны, лечение, аутоТГСК, поддерживающая терапия.

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Лимфома Ходжкина и «новый старый» бендамустин

КЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ЛИМФОИДНЫХ ОПУХОЛЕЙ , , ,

С.С. Шкляев, В.В. Павлов

ФГБУ МРНЦ МЗ РФ, Обнинск, Российская Федерация

РЕФЕРАТ

Лимфома Ходжкина — злокачественная опухоль, которая с течением времени превратилась из фатальной неизлечимой болезни в успешно вылечиваемую в подавляющем большинстве случаев. Тем не менее прогноз у пациентов с рефрактерным и рецидивирующим течением заболевания нередко плохой и угрожающий жизни, в особенности в тех случаях, когда прогрессирование опухоли продолжается после высокодозной химиотерапии с трансплантацией аутологичных гемопоэтических стволовых клеток или, у некоторых пациентов, даже после аллогенной трансплантации костного мозга. Бендамустин — «новый старый» цитостатический препарат, который может эффективно применяться при лечении таких больных. Представляемый нами обзор литературы отводит важное место целому ряду новых возможных вариантов лечения лимфомы Ходжкина с применением бендамустина.

Ключевые слова: лимфома Ходжкина, рефрактерное и рецидивирующее течение, лечение, бендамустин.

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Диффузная В-крупноклеточная лимфома яичка в детском возрасте

КЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ЛИМФОИДНЫХ ОПУХОЛЕЙ , , ,

Т.Т. Валиев1, А.М. Ковригина2, И.Н. Серебрякова3, Е.В. Михайлова1, А.В. Попа1, Г.Л. Менткевич1

 -НИИ Детской онкологии и гематологии ФГБУ «РОНЦ им. Н.Н. Блохина» РАМН, Москва

2-ФГБУ «Гематологический научный центр Министерства здравоохранения РФ», Москва, Российская Федерация

3-НИИ Клинической онкологии ФГБУ «РОНЦ им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

Неходжкинские лимфомы с первичным поражением яичка представляют собой редкую гетерогенную группу лимфоидных опухолей, программы терапии которых до конца не разработаны. У взрослых лимфомы яичка характеризуются агрессивным течением, частым рецидивированием, метастазированием в ЦНС и плохим ответом на стандартную терапию. В детском возрасте они, по литературным данным, представлены в виде описания единичных наблюдений. В статье приводится описание диффузной В-крупноклеточной лимфомы яичка у 10-летнего больного. Подробно обсуждается успешно проведенное лечение и роль программной интенсивной химиотерапии.

Ключевые слова: лимфома яичка, диагностика, лечение, дети

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ЛИТЕРАТУРА

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Фолликулярная лимфома: современные тенденции и мой выбор

МОЙ ВЫБОР ,

Г.С. Тумян

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

В этой первой публикации из серии «Мой выбор» обобщены современные данные по диагностике и лечению фолликулярной лимфомы и предложен алгоритм диагностических и лечебных мероприятий. Это позволит гематологу индивидуализировать лечение больных как при первичном обращении, так и рецидивах заболевания. Рассмотрены вопросы определения опухолевой нагрузки, трансформации болезни, кратко представлены различные варианты фолликулярной лимфомы.

Ключевые слова: фолликулярная лимфома, лечение

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ЛИТЕРАТУРА

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Лечение распространенных стадий лимфомы Ходжкина: обзор литературы

ОБЗОРЫ , , , ,

А.А. Леонтьева, Е.А. Демина

ФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина», Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Анна Александровна Леонтьева, аспирант, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-90-89; e-mail: aurevoir-nut@yandex.ru

Для цитирования: Леонтьева А.А., Демина Е.А. Лечение распространенных стадий лимфомы Ходжкина: обзор литературы. Клиническая онкогематология. 2015;8(3):255–66.

РЕФЕРАТ

В последнее десятилетие крупные исследовательские центры в Европе и США, имеющие большие базы данных, провели комплексный анализ эффективности лечебных программ, поздних осложнений терапии и показателей длительной выживаемости больных с распространенными стадиями лимфомы Ходжкина. Этот анализ позволил разработать и предложить практической медицине новые программы, отличающиеся большей эффективностью, и начать поиск менее токсичных вариантов лечения. Однако в отечественной литературе такой комплексный анализ не представлен. Имеющиеся публикации и научные исследования освещают лишь отдельные аспекты диагностики и лечения лимфомы Ходжкина, или в них выборочно обсуждаются проблемы осложнений. Предлагаемый обзор позволяет читателю проследить путь, пройденный в лечении распространенных стадий лимфомы Ходжкина за 75 лет — от абсолютно пессимистического прогноза до современных высоких результатов с дальнейшим совершенствованием терапии этой злокачественной опухоли.

Ключевые слова: лимфома Ходжкина, распространенные стадии, лечение, эффективность, токсичность.

Получено: 20 февраля 2015 г.

Принято в печать: 28 мая 2015 г.

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