Инвазивный микоз, обусловленный Aureobasidium pullulans, у ребенка с острым миелобластным лейкозом (собственное клиническое наблюдение)

Н.С. Багирова1, А.В. Попа1, Т.С. Богомолова2, Н.А. Батманова1, Н.В. Дмитриева1, И.Н. Петухова1, Е.Н. Соколова1

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

2 ФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России, ул. Кирочная, д. 41, Санкт-Петербург, Российская Федерация, 191015

Для переписки: Наталия Сергеевна Багирова, д-р мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: 8(499)324-18-60; e-mail: nbagirova@mail.ru

Для цитирования: Багирова Н.С., Попа А.В., Богомолова Т.С. и др. Инвазивный микоз, обусловленный Aureobasidium pullulans, у ребенка с острым миелобластным лейкозом (собственное клиническое наблюдение). Клиническая онкогематология. 2018;11(3):259–64.

DOI: 10.21320/2500-2139-2018-11-3-259-264


РЕФЕРАТ

Тяжелая микотическая инфекция, возникающая преимущественно у пациентов со сниженным иммунитетом, часто осложняет течение основного онкогематологического заболевания. Впервые в отечественной литературе мы представляем клинико-микробиологические особенности инвазивного микоза, обусловленного Aureobasidium pullulans, у ребенка с острым миелобластным лейкозом, получавшего цитостатическую и противогрибковую терапию с благоприятным исходом.

Ключевые слова: Aureobasidium pullulans, острый миелобластный лейкоз, инвазивный микоз.

Получено: 15 января 2018 г.

Принято в печать: 8 апреля 2018 г.

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ЛИТЕРАТУРА

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Прогностическое значение и корреляция динамики гиперэкспрессии гена WT1 и мутации гена NPM1 у пациентов с острым миелобластным лейкозом

Л.Л. Гиршова, И.Г. Будаева, Е.Г. Овсянникова, С.О. Кузин, Д.В. Моторин, Р.Ш. Бадаев, Д.Б. Заммоева, В.В. Иванов, К.В. Богданов, О.С. Писоцкая, Ю.В. Миролюбова, Т.С. Никулина, Ю.А. Алексеева, А.Ю. Зарицкий

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

Для переписки: Ирина Гармаевна Будаева, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341; тел.: +7(931)351-07-06; e-mail: irina2005179@mail.ru

Для цитирования: Гиршова Л.Л., Будаева И.Г., Овсянникова Е.Г. и др. Прогностическое значение и корреляция динамики гиперэкспрессии гена WT1 и мутации гена NPM1 у пациентов с острым миелобластным лейкозом. Клиническая онкогематология. 2017;10(4):485–93.

DOI: 10.21320/2500-2139-2017-10-4-485-493


РЕФЕРАТ

Актуальность. Острый миелобластный лейкоз (ОМЛ) с мутацией NPM1 составляет 30 % всех ОМЛ и характеризуется благоприятным прогнозом, за исключением случаев с мутацией FLT3-ITD. Несмотря на благоприятный прогноз, вероятность развития рецидивов у пациентов с мутацией NPM1 может принципиально отличаться. В связи с этим все большую актуальность приобретает возможность оценки минимальной остаточной болезни (МОБ) на фоне программной химиотерапии и на этапе последующего наблюдения. Такой подход позволит прогнозировать чувствительность опухолевого клона к химиотерапии.

Цель. Оценить результаты использования высокоспецифичного (мутации NPM1) и более универсального неспецифичного (гиперэкспрессия гена WT1) маркеров для оценки МОБ, а также выявить корреляцию в динамике изменений уровней NPM1 и WT1 на разных этапах терапии и после ее окончания в период наблюдения.

Материалы и методы. В исследование включено 14 пациентов c ОМЛ. У всех больных имели место мутация NPM1 и гиперэкспрессия гена WT1. У 50 % пациентов обнаруживались дополнительные молекулярные маркеры (гиперэкспрессия BAALC, мутации FLT3-ITD, DNMT3A, MLL). Представлен длительный мониторинг уровней экспрессии WT1 и мутации NPM1 методом ПЦР в режиме реального времени.

Результаты. Медиана редукции уровня NPM1 после индукционной терапии составила 3 log. У всех пациентов данной группы развились рецидивы, присутствовала мутация NPM1, отмечались более низкие показатели общей (ОВ) и безрецидивной выживаемости (БРВ), что статистически значимо коррелирует с наличием прогностически неблагоприятных молекулярных маркеров. Не отмечено статистически значимых различий БРВ в группах с редукцией уровня экспрессии WT1 < или > 2 log на 28-й день лечения. В то же время при редукции уровня экспрессии WT1 ≥ 2 log выявлена статистически значимая разница в развитии раннего рецидива в зависимости от уровня снижения NPM1 (≥ или < 3 log). БРВ была более долгосрочной у пациентов с уровнем экспрессии WT1 < 100/104 копий ABL на 28-й день и WT1 < 250/104 копий ABL на 14-й день от начала терапии. Уровень экспрессии WT1 был значительно ниже на 14-й и 28-й дни у пациентов с редукцией NPM1 > 3 log на 28-й день. Снижение экспрессии WT1 < 100/104 копий ABL на 28-й день чаще встречалось у пациентов с изолированной мутацией NPM1 в отличие от больных с дополнительными неблагоприятными молекулярными маркерами.

Заключение. Уровень редукции NPM1 после индукционной терапии может служить достоверным предиктором, влияющим на показатели БРВ и ОВ. Выявлена корреляция между степенью редукции NPM1 и наличием дополнительных молекулярных маркеров. При сравнении универсального (гиперэкспрессия WT1) и высокоспецифичного (мутация NPM1) маркеров NPM1 оказался более чувствительным маркером. В работе подтверждено прогностическое значение более низкого порогового уровня WT1 на 28-й день лечения (100/104 копий ABL) и впервые показано влияние на результаты терапии ранней оценки редукции экспрессии WT1 на 14-й день индукционного курса.

Ключевые слова: острый миелобластный лейкоз, ОМЛ, NPM1, WT1, молекулярный мониторинг.

Получено: 22 февраля 2017 г.

Принято в печать: 26 мая 2017 г.

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ЛИТЕРАТУРА

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Острый миелобластный лейкоз и миелодиспластический синдром: применение азацитидина с профилактической и превентивной целью после аллогенной трансплантации гемопоэтических стволовых клеток

В.Н. Овечкина1, С.Н. Бондаренко1, Е.В. Морозова1, И.С. Моисеев1, О.А. Слесарчук1, А.Г. Смирнова1, О.С. Успенская2, Я.В. Гудожникова1, А.А. Осипова1, В.С. Сергеев1, Н.Н. Мамаев1, Л.С. Зубаровская1, Б.В. Афанасьев1

1 НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

2 ГБУЗ «Ленинградская областная клиническая больница», пр-т Луначарского, д. 45–49, Санкт-Петербург, Российская Федерация, 194291

Для переписки: Варвара Николаевна Овечкина, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; тел.: 8(812)338-62-72; e-mail: ovetchkina@gmail.com

Для цитирования: Овечкина В.Н., Бондаренко С.Н., Морозова Е.В. и др. Острый миелобластный лейкоз и миелодиспластический синдром: применение азацитидина с профилактической и превентивной целью после аллогенной трансплантации гемопоэтических стволовых клеток. Клиническая онкогематология. 2017;10(1):45–51.

DOI: 10.21320/2500-2139-2017-10-1-45-51


РЕФЕРАТ

Цель. Оценить эффективность превентивной и профилактической посттрансплантационной терапии азацитидином (5-AZA) у пациентов с высоким риском посттрансплантационного рецидива.

Методы. В исследование, выполненное методом парного анализа, включено 136 пациентов: 68 из них после аллоТГСК получали 5-AZA, 68 составили группу исторического контроля. 5-AZA назначался с профилактической или превентивной целью. Результаты оценивались с учетом ОВ, ЧР, БСВ, ЛНЗ и ВБРР.

Результаты. В группе терапии 5-AZA и группе сравнения 1-летняя общая выживаемость (ОВ) составила 76 (95% ДИ 60–84 %) и 44 % (95% ДИ 33–55 %) (= 0,001) соответственно; 2-летняя ОВ — 63 (95% ДИ 39–67 %) и 37 (95% ДИ 26–48 %) (= 0,007); 1-летняя частота рецидивов (ЧР) — 34 (95% ДИ 22–46 %) и 51 % (95% ДИ 38–64 %) (= 0,02); 1- и 2-летняя летальность, не связанная с заболеванием (ЛНЗ), была одинакова — 5 (95% ДИ 0,1–14,0 %) и 25 % (95% ДИ 13–37 %) (= 0,005); 1-летняя бессобытийная выживаемость (БСВ) — 76 (95% ДИ 61–85 %) и 44 % (95% ДИ 33–55 %) (= 0,001); 2-летняя БСВ — 63 (95% ДИ 39–67 %) и 37 % (95% ДИ 26–48 %) (= 0,01); 1-летняя выживаемость без рецидивов и РТПХ (ВБРР) — 55 (95% ДИ 41–69 %) и 28 % (95% ДИ 17–39 %) (= 0,001); 2-летняя ВБРР — 47 (95% ДИ 32–62 %) и 27 % (95% ДИ 17–37 %) соответственно (= 0,002).

Заключение. Применение 5-AZA с профилактической и превентивной целью после аллоТГСК не увеличивает риск развития РТПХ и ЛНЗ, не подавляет РТПЛ и может использоваться в комбинации с инфузией донорских лимфоцитов (ИДЛ) в безопасном режиме. Терапия 5-AZA безопасна в ранний срок после аллоТГСК. Препарат не подавляет развитие РТПЛ и может использоваться у пациентов с высоким риском для предотвращения ранних посттрансплантационных рецидивов. Применение 5-AZA совместно с ИДЛ не увеличивает частоту тяжелой РТПХ.

Ключевые слова: острый миелобластный лейкоз, миелодиспластический синдром, аллогенная трансплантация гемопоэтических стволовых клеток, гипометилирующая терапия, азацитидин.

Получено: 18 июля 2016 г.

Принято в печать: 17 декабря 2016 г.

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ЛИТЕРАТУРА

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Молекулярный мониторинг уровня транскрипта RUNX1-RUNX1T1 при острых миелобластных лейкозах на фоне терапии

Л.Л. Гиршова, Е.Г. Овсянникова, С.О. Кузин, Е.Н. Горюнова, Р.И. Вабищевич, А.В. Петров, Д.В. Моторин, Д.В. Бабенецкая, В.В. Иванов, К.В. Богданов, И.В. Холопова, Т.С. Никулина, Ю.В. Миролюбова, Ю.А. Алексеева, А.Ю. Зарицкий

ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341

Для переписки: Екатерина Геннадьевна Овсянникова, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341; тел.: +7(921)313-68-35; e-mail: katrin51297@mail.ru

Для цитирования: Гиршова Л.Л., Овсянникова Е.Г., Кузин С.О. и др. Молекулярный мониторинг уровня транскрипта RUNX1-RUNX1T1 при острых миелобластных лейкозов на фоне терапии. Клиническая онкогематология. 2016;9(4):456–64.

DOI: 10.21320/2500-2139-2016-9-4-456-464


РЕФЕРАТ

Актуальность. Современные подходы к терапии острых миелобластных лейкозов (ОМЛ) заключаются в достижении максимальной редукции опухоли и, соответственно, эрадикации лейкозного клона. За исключением случаев изолированной молекулярной перестройки RUNX1-RUNX1T1, целью терапии является достижение неопределяемого уровня таргетного (исследуемого) гена.

Цель. Оценить динамику уровня RUNX1-RUNX1T1 и соответствующих клинических проявлений в ходе мониторинга на различных этапах программной терапии и после ее завершения.

Методы. В работе представлено описание 10 наблюдений ОМЛ с изолированной экспрессией RUNX1-RUNX1T1 (n = 4) и в сочетании с различными молекулярными и цитогенетическими аномалиями (n = 6). Кроме того, представлено наблюдение длительного мониторинга экспрессии гена методом количественного определения RUNX1-RUNX1T1 с помощью ПЦР в реальном времени.

Результаты. Частота рецидивов в группе со снижением уровня экспрессии RUNX1-RUNX1T1 ³ 2 log составила 75 % в сравнении с пациентами, у которых был меньше уровень снижения транскрипта с частотой рецидивов 0 % (= 0,05). Нарастание уровня RUNX1-RUNX1T1 на фоне сохранения костномозговой ремиссии более чем на 1 log совпадало с развитием костномозгового рецидива в течение 5–18 нед. Кроме того, возможно длительное сохранение определенного уровня транскрипта после завершения программной терапии без развития рецидивов.

Заключение. В работе подвергнуты анализу возможные молекулярные предпосылки различных клинических исходов ОМЛ у больных с длительной персистенцией транскрипта RUNX1-RUNX1T1. Это, возможно, позволит сформировать индивидуализированный подход к пациентам с ОМЛ.


Ключевые слова: острый миелобластный лейкоз, ОМЛ, RUNX1-RUNX1T1, молекулярный мониторинг.

Получено: 5 апреля 2016 г.

Принято в печать: 18 апреля 2016 г.

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Мутации генов при острых миелоидных лейкозах

О.В. Блау

Клиника Шарите, Берлинский медицинский университет, ул. Хинденбургдамм, д. 30, Берлин, Германия, 12200

Для переписки: Ольга Владимировна Блау, д-р мед. наук, Department of Hematology, Oncology and Tumorimmunology, Charite University School of Medicine, Hindenburgdamm 30, 12200, Berlin, Germany; e-mail: olga.blau@charite.de.

Для цитирования: Блау О.В. Мутации генов при острых миелоидных лейкозах. Клиническая онкогематология. 2016;9(3):245-56.

DOI: 10.21320/2500-2139-2016-9-3-245-256


РЕФЕРАТ

Острый миелобластный лейкоз (ОМЛ) — клональное злокачественное заболевание, характеризующееся неэффективным гемопоэзом. Большинство больных ОМЛ имеют различные цитогенетические и молекулярно-генетические повреждения, которые сочетаются с определенными биологическими и клиническими особенностями заболевания. Примерно у 50–60 % больных de novo и у 80–95 % больных вторичными ОМЛ обнаруживаются хромосомные изменения. Следует отметить, что структурные цитогенетические аберрации являются наиболее частыми маркерами и встречаются примерно в 40 % случаев ОМЛ de novo. Достаточно большая группа больных с нормальным кариотипом (НК-ОМЛ), формально относящаяся к категории промежуточного риска, является крайне гетерогенной в отношении прогноза течения заболевания. В действующие прогностические классификации ОМЛ включены сегодня только некоторые мутации, характеризующиеся известным прогностическим значением, в частности NPM1, FLT3 и C/EBPa. Пациенты с NPM1, но без мутаций FLT3-ITD или с мутациями C/EBPa характеризуются благоприятным прогнозом заболевания, а с мутацией FLT3-ITD — неблагоприятным. Недавно выявлен новый класс мутаций, при которых повреждаются гены, ответственные за эпигенетические процессы регуляции генома, в частности метилирование ДНК или модификацию гистонов. Среди них наиболее изученными к настоящему времени являются мутации в генах DNMT3A, IDH1/2, TET2 и некоторых других. В целом ряде исследований показан неблагоприятный прогностический эффект мутации DNMT3A при ОМЛ. Что касается прогностического значения IDH1/2, то данный вопрос еще не до конца ясен. На прогноз заболевания влияет ряд биологических факторов, в т. ч. сочетание с цитогенетическими аберрациями и другими мутациями, особенно FLT3 и NPM1. Число исследований, посвященных генетическим мутациям при ОМЛ, постоянно растет. Накопленные к настоящему времени знания о генетических изменениях при ОМЛ подтверждают их роль в возникновении и развитии заболевания.


Ключевые слова: острый миелобластный лейкоз, ОМЛ, кариотип, цитогенетические аберрации, мутации генов, прогноз.

Получено: 23 января 2016 г.

Принято в печать: 4 апреля 2016 г.

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