L-аспарагиназа

Тромбогеморрагические осложнения при лечении больных острым лимфобластным лейкозом L-аспарагиназой

ОСЛОЖНЕНИЯ ПРОТИВООПУХОЛЕВОГО ЛЕЧЕНИЯ , , , , , , ,

Г.М. Галстян, О.А. Полеводова, А.В. Баженов, В.В. Троицкая, О.А. Гаврилина, Д.Г. Гительзон, А.Э. Васильев, Е.Н. Паровичникова

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

Для переписки: Геннадий Мартинович Галстян, д-р мед. наук, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; тел.: +7(916)488-50-73; e-mail: gengalst@gmail.com

Для цитирования: Галстян Г.М., Полеводова О.А., Баженов А.В. и др. Тромбогеморрагические осложнения при лечении больных острым лимфобластным лейкозом L-аспарагиназой. Клиническая онкогематология. 2018;11(1):89-99.

DOI: 10.21320/2500-2139-2018-11-1-89-99

РЕФЕРАТ

Настоящая статья представляет собой обзор литературы, посвященный применению L-аспарагиназы (АСП) при остром лимфобластном лейкозе (ОЛЛ), с описанием 2 собственных клинических наблюдений. Лечение АСП при проведении индукции ремиссии осложнилось у пациентов венозными тромбозами и кровоизлиянием в ЦНС. В обоих случаях эти осложнения возникли на фоне сниженной плазменной активности антитромбина III (АТ), гипофибриногенемии и тромбоцитопении. Обсуждаются факторы риска возникновения тромбогеморрагических осложнений у больных ОЛЛ во время лечения АСП, роль в их развитии сочетанной терапии АСП с антрациклинами, пероральными контрацептивами, глюкокортикостероидами, наличия тромбофилии и центрального венозного катетера. Описаны возможные механизмы развития тромбозов, определены наиболее вероятные сроки их возникновения, локализация. В статье приводятся различные варианты профилактики и лечения тромбогеморрагических осложнений у больных ОЛЛ во время лечения АСП. Рекомендуется у всех больных ОЛЛ, получающих АСП, исследовать в плазме концентрацию фибриногена и активность АТ до начала лечения, на 3-й день после введения препарата и далее каждые 5–7 дней на протяжении 3 нед. после введения. Новые пероральные антикоагулянты не зависят от активности АТ в крови и могут использоваться для профилактики и лечения тромботических осложнений, связанных с АСП. Приводятся рекомендации по коррекции содержания АТ и гипофибриногенемии.

Ключевые слова: L-аспарагиназа, осложнения, тромбоз, тромбоэластография, антитромбин III, гипофибриногенемия, тромбоцитопения, новые пероральные антикоагулянты.

Получено: 16 августа 2017 г.

Принято в печать: 27 октября 2017 г.

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Ферментные препараты в онкогематологии: актуальные направления экспериментальных исследований и перспективы клинического применения

ОБЗОРЫ , , , , , ,

В.С. Покровский, Е.М. Трещалина

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

РЕФЕРАТ

Последние годы в области разработки новых противоопухолевых препаратов на основе ферментов продемонстрированы существенные достижения. Помимо L-аспарагиназы, которая применяется в онкогематологии уже более 30 лет, два фермента — L-аргининдезиминаза и ранпирназа — прошли несколько этапов клинических исследований. Для целого ряда ферментов показана противоопухолевая активность на доклиническом этапе в экспериментах in vivo: L-метионин-гамма-лиаза, L-лизин-альфа-оксидаза, биназа. В настоящем обзоре представлены ферменты, продемонстрировавшие на различных этапах исследований противоопухолевую активность, и перспективы их использования в онкогематологии.

Ключевые слова: противоопухолевые ферменты, L-аспарагиназа, L-метионин-гамма-лиаза, L-лизин-альфа-оксидаза, L-аргининдезиминаза, L-фенилаланин-аммиак-лиаза, ранпирназа.

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