Pediatric Hematology/Oncology and Immunopathology

Вопросы гематологии/онкологии и иммунопатологии в педиатрии

1726-17082414-9314

Fund Doctors, Innovations, Science for Children

538

10.24287/1726-1708-2021-20-3-12-25

ORIGINAL ARTICLES

ОРИГИНАЛЬНЫЕ СТАТЬИ

Thrombopoietin receptor agonists for the treatment of severe persistent and chronic immune trombocytopenia in children: clinical data of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology

Агонисты рецепторов тромбопоэтина в лечении тяжелой затяжной и хронической иммунной тромбоцитопении у детей: клинические данные НМИЦ ДГОИ им. Дмитрия Рогачева

https://orcid.org/0000-0001-8404-1800

Suntsova

E. V.

Сунцова

Е. В.

Russian Federation

Moscow

Сунцова Елена Викторовна, научный сотрудник отдела депрессий кроветворения, миелоидных лейкозов, редких и наследственных болезней

117997, Москва, ул. Саморы Машела, 1

elena.suncova@fccho-moscow.ru

https://orcid.org/0000-0002-0016-6698

Maschan

A. A.

Масчан

А. А.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-8952-8386

Mironenko

O. N.

Мироненко

О. Н.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-7130-8596

Baydildina

D. D.

Байдильдина

Д. Д.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-0813-5626

Kalinina

I. I.

Калинина

И. И.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-7837-6890

Korsantya

M. N.

Корсантия

М. Н.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0003-2787-6005

Kotskaya

N. N.

Коцкая

Н. Н.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-8586-8586

Kuzminova

Z. A.

Кузьминова

Ж. А.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-8880-9266

Ovsyannikova

G. S.

Овсянникова

Г. С.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-1258-8281

Petrova

U. N.

Петрова

У. Н.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-2057-2036

Pshonkin

A. V.

Пшонкин

А. В.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-7918-680X

Sadovskaya

M. N.

Садовская

М. Н.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-2958-1705

Salimova

T. Yu.

Салимова

Т. Ю.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-2062-086X

Trubina

N. M.

Трубина

Н. М.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0003-4567-1871

Fedorova

D. V.

Федорова

Д. В.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-2322-5734

Novichkova

G. A.

Новичкова

Г. А.

Russian Federation

Moscow

Москва

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России

08102021

203

12250710202107102021

2021

«D. Rogachev NMRCPHOI»

ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России

https://creativecommons.org/licenses/by/4.0

https://hemoncim.com/jour/article/view/538

Thrombopoietin receptor agonists (TPO-RA) – romiplostim and eltrombopag – changed considerably the therapeutic options for severe persistent and chronic immune thrombocytopenia (ITP). The article presents the results of a retrospective study of TPO-RA efficacy and safety in patients under 18 years of age. The study was approved by the Independent Ethics Committee and Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Sixty-eight children had a total of 89 courses of TPO-RA (44 romiplostim and 45 eltrombopag). Their median age was 6.5 years. The median ITP duration was 15.8 months. All patients received previous ITP therapy (1–6 lines). Before the initiation of TPO-RA, the majority of patients had thrombocytopenia with bleeding. In most cases, the platelet response was achieved within the first 2 months of treatment. The average effective doses of romiplostim and eltrombopag were 10 mg/kg per week and 75 mg per day, respectively. Half of patients in romiplostim group and 62% of patients in eltrombopag group did not require extra therapy. The majority of patients (75.6–81.8%) achieved an overall response, but only near 50% achieved a durable (more than 24 weeks) platelet response. Six patients sustained the response after TPO-RA discontinuation. The most common adverse events (AE) of TPO-RA therapy were transient elevation in hepatic enzymes in eltrombopag group (28.9%) and thrombocytosis (18.2–22.2%) in both groups. In 6 cases the therapy was discontinued due to AEs. Two AEs were serious. Our results demonstrate that TPO-RA could safely increase platelet counts and decrease the risk of spontaneous life-threatening bleeding in nearly half of children with severe persistent and chronic ITP. TPO-RA could help to avoid long-term immunosuppressive therapy and splenectomy or delay them and the ITP remission is possible in some cases.

Агонисты тромбопоэтиновых рецепторов (ТПО-РА) – ромиплостим и элтромбопаг – значительно изменили возможности медикаментозной терапии тяжелой затяжной и хронической иммунной тромбоцитопении (ИТП). В настоящей статье представлены результаты ретроспективного исследования эффективности и безопасности ТПО-РА у пациентов в возрасте до 18 лет. Исследование поддержано независимым этическим комитетом и утверждено решением ученого совета ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. В исследование были включены 68 пациентов, которым проведено 89 курсов ТПО-РА (44 курса ромиплостима и 45 курсов элтромбопага). Медиана возраста пациентов на момент начала терапии – 6,5 года. Все пациенты получали предшествующую ИТП-направленную терапию 1–6-й линий. Медиана длительности заболевания составила 15,8 мес. Перед началом терапии ТПО-РА большинство пациентов имели экстремальную тромбоцитопению с симптомами кровоточивости. Тромбоцитарный ответ на ТПО-РА в большинстве случаев достигался в первые 2 мес от начала лечения. Терапевтически эффективная доза ромиплостима составила в среднем 10 мкг/кг/нед, элтромбопага – 75 мг/сут. Половина пациентов группы ромиплостима и 62% больных группы элтромбопага не нуждались в дополнительной терапии. Большинство пациентов (75,6–81,8%) достигли общего ответа, но только около 50% – длительного тромбоцитарного ответа (> более 24 нед). Шесть пациентов сохранили полный ответ после отмены ТПО-РА. Все нежелательные явления (НЯ) терапии ТПО-РА были транзиторными, наиболее частые из них тромбоцитоз (18,2–22,2%) и повышение печеночных трансаминаз при применении элтромбопага (28,9%). По причине развития НЯ терапия ТПО-РА отменена в 6 случаях. Два НЯ расценены как серьезные. Результаты исследования показали, что ТПО-РА у детей с тяжелой затяжной и хронической ИТП могут безопасно повышать число тромбоцитов, снижая риск развития спонтанной угрожающей жизни кровоточивости, у половины пациентов. Применение ТПО-РА позволяет избежать назначения длительной иммуносупрессивной терапии и выполнения спленэктомии либо отодвинуть их на более поздние сроки, в исключительных случаях возможно добиться ремиссии ИТП.

immune thrombocytopeniachildrenthrombopoietin receptor agonistsromiplostimeltrombopag

иммунная тромбоцитопениядетиагонисты тромбопоэтиновых рецепторовромиплостимэлтромбопаг

Авторы статьи выражают глубокую благодарность д-ру мед. наук, профессору ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России Самочатовой Елене Владимировне за поддержку и помощь при подготовке статьи.

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