Клиническая эффективность молекулярно-направленной терапии в фазе акселерации хронического миелолейкоза
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Диссертация
Впервые дана объективная оценка клинической эффективности монотерапии гливеком — первым представителем нового класса препаратов — ингибиторов тирозинкиназ. Установлена существенная взаимосвязь восстановления Ph-негативного гемопоэза при лечении гливеком и 2-летней выживаемостью, что доказывает целесообразность его использования в лечении больных в фазе акселерации XMJI. Выделены неблагоприятные… Читать ещё >
Содержание
- Список сокращений
- ГЛАВА I. ОБЗОР ЛИТЕРАТУРЫ
- 1. 1. Основные эпидемиологические сведения о ХМЛ
- 1. 2. Современные представления об этиопатогенезе ХМЛ
- 1. 2. 1. Строение филадельфийской хромосомы
- 1. 2. 2. Варианты BCR-ABL и их влияние на фенотип заболевания
- 1. 2. 3. Функциональные домены и физиологическая роль ABL
- 1. 2. 4. Функциональные домены и физиологическая роль BCR
- 1. 2. 5. Механизм активации Bcr-Abl
- 1. 2. 6. Влияние Всг-АЫ на сигнальные пути, ответственные за 16 пролиферацию и дифференцировку клеток
- 1. 2. 7. Влияние Всг-АЫ на апоптоз
- 1. 2. 8. Влияние Всг-АЫ на клеточную адгезию
- 1. 2. 9. BCR-ABL-индуцированная нестабильность клеточного генома
- 1. 2. 10. Последствия образования BCR-ABL
- 1. 3. Лечение ХМЛ
- 1. 3. 1. История создания гливека
- 1. 3. 2. Механизм действия гливека
- 1. 3. 3. Клинические испытания I фазы
- 1. 4. Критерии дифференциации фаз ХМЛ
- 1. 5. Лечение больных в ФА ХМЛ
- 1. 6. Механизмы резистентности к гливеку
- ГЛАВА II. МАТЕРИАЛЫ И МЕТОДЫ ИССЛЕДОВАНИЯ
- 2. 1. Критерии включения
- 2. 2. Общий дизайн исследования
- 2. 3. Методы исследования
- 2. 4. Оценка эффективности терапии
- 2. 5. Методика оценки качества жизни у больных ХМЛ в ФА
- 2. 6. Компьютерная база данных и статистическая обработка материала
- ГЛАВА III. РЕЗУЛЬТАТЫ СОБСТВЕННЫХ ИССЛЕДОВАНИЙ. АНАЛИЗ 47 ИНИЦИАЛЬНЫХ ХАРАКТЕРИСТИК БОЛЬНЫХ С ХМЛ
- 3. 1. Анализ анамнестических данных
- 3. 2. Анализ инициальных жалоб
- 3. 3. Результаты оценки инициального клинического статуса
- 3. 4. Оценка структуры и частоты клинико-лабораторных признаков 52 фазы акселерации
- 3. 4. 1. Анализ клинических характеристик больных
- 3. 4. 2. Анализ гематологических показателей по данным 53 периферической крови и костномозгового кроветворения
- 3. 4. 3. Анализ инициальных цитогенетических данных
- 4. 1. Оценка клинической эффективности
- 4. 2. Оценка гематологической эффективности
- 4. 3. Оценка цитогенетического ответа на терапию гливеком
- 4. 4. Клинико-гематологические характеристики, прогнозирующие 72 ответ на лечение гливеком
- 4. 5. Анализ выживаемости пациентов в ФА ХМЛ на монотерапии гливеком
- 4. 6. Выделение других неблагоприятных прогностических признаков, 79 влияющих на снижение эффективности лечения гливеком и прогрессию XMJ
- 5. 1. Анализ проявлений гематологической токсичности
- 5. 2. Анализ проявлений негематологической токсичности
- 5. 3. Влияние сопутствующей патологии на частоту возникновения 95 побочных эффектов гливека
- 5. 4. Изменения дозового режима гливека в связи с развитием 97 токсичности
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