Pediatric Hematology/Oncology and Immunopathology

Вопросы гематологии/онкологии и иммунопатологии в педиатрии

1726-17082414-9314

Fund Doctors, Innovations, Science for Children

656

10.24287/1726-1708-2022-21-3-100-114

CLINICAL OBSERVATIONS

КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ

Acute lymphoblastic leukemia with the t(17;19) translocation: hope has appeared! Multimodal immunotherapy in a 3-year-old child with refractory disease: a case report

Острый лимфобластный лейкоз с транслокацией t(17;19): надежда появилась! Описание случая мультимодальной иммунотерапии у ребенка 3 лет с рефрактерным течением заболевания

https://orcid.org/0000-0002-7461-0050

Litvinov

D. V.

Литвинов

Д. В.

Russian Federation

Dmitry V. Litvinov, Chief Physician

1 Samory Mashela St., 117997, Moscow, Russia

Литвинов Дмитрий Витальевич, главный врач

117997, Москва, ул. Саморы Машела, 1

dmitry.litvinov@fccho-moscow.ru

Tesakov

I. P.

Тесаков

И. П.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0003-0520-5630

Shelikhova

L. N.

Шелихова

Л. Н.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-7265-0414

Khachatryan

L. A.

Хачатрян

Л. А.

Russian Federation

Moscow

Москва

Zerkalenkova

E. A.

Зеркаленкова

Е. А.

Russian Federation

Moscow

Москва

Olshanskaya

Yu. V.

Ольшанская

Ю. В.

Russian Federation

Moscow

Москва

Komkov

A. Yu.

Комков

А. Ю.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-0889-6986

Popov

A. M.

Попов

А. М.

Russian Federation

Moscow

Москва

Mikhaylova

E. V.

Михайлова

Е. В.

Russian Federation

Moscow

Москва

Remizov

A. N.

Ремизов

А. Н.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-4779-1896

Myakova

N. V.

Мякова

Н. В.

Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-9670-3728

Rumyantseva

Yu. V.

Румянцева

Ю. В.

Russian Federation

Moscow

Москва

Karachunskiy

A. I.

Карачунский

А. И.

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

15102022

213

1001141510202215102022

2022

«D. Rogachev NMRCPHOI»

ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России

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

https://hemoncim.com/jour/article/view/656

Acute lymphoblastic leukemia (ALL) with translocation t(17;19)(q21-q22;p13) TCF3::HLF (E2A::HLF) accounts for less than 1% of childhood B-lineage ALL. Since the first description, patients with this type of ALL are stratified into high-risk group. The disease often has a unique clinical presentation with disseminated intravascular coagulation and hypercalcemia, that are uncommon in other types of B-lineage ALL. This type of ALL is characterized by an extremely poor prognosis despite intensive treatment and hematopoietic stem cell transplantation (HSCT) in the first remission. In the last decade, some new data on the mechanisms of leukemogenesis in this type of ALL made it possible to come closer to understanding the reasons for the high refractoriness to chemotherapeutic agents. Along with the reports on the possible effectiveness of the BCL-2 (venetoclax) and Aurora kinase A (alisertib) inhibitors in this type of ALL, cellular immunotherapy (various chimeric antigen receptor (CAR)-T cell constructs), anti-CD19 (blinatumomab) and anti-CD22 (inotuzumab ozogamicin) monoclonal antibodies appear promising in the treatment of this disease. To date, there are neither published data on direct comparisons of the effectiveness of these methods nor specific recommended therapy protocols for these patients. It is also unclear if the new therapeutic approaches can completely replace HSCT or they only increase relapse-free survival after it. Here, we review the data on this translocation published in the medical literature and present a case report of a 3-year-old boy with this type of leukemia, who did not respond to four-component induction therapy according to the ALL-MB 2015 Protocol and received anti-CD19 CAR-T therapy with the achievement of the first MRD (minimal residual disease)-negative remission, which lasted 11 months. After MRD-relapse and unsuccessful attempt at therapy with autologous CD19/CD22 CAR-T cells, the patient developed an extended isolated bone marrow relapse. He achieved the second MRD-negative remission after reinduction therapy with inotuzumab ozogomycin and received allogeneic HSCT from a related donor. At the time of writing, the patient is in complete molecular remission for 16 months after transplantation. The patient's parents have consented to the use of de-identified clinical information and photos of the patient in scientific research and publications.

Острый лимфобластный лейкоз (ОЛЛ) с транслокацией t(17;19)(q21–q22;p13) TCF3::HLF (E2A::HLF) составляет не более 1% острых лейкозов из В-клеток-предшественников у детей и с самого момента описания относится всеми исследователями к группе высокого риска. Заболевание в большинстве случаев имеет уникальную клиническую презентацию с развитием синдрома диссеминированного внутрисосудистого свертывания и гиперкальциемии, не характерных для других вариантов ОЛЛ из В-линейных клеток-предшественников. Данная форма чаще всего поражает детей и характеризуется экстремально плохим прогнозом даже при условии использования интенсивной химиотерапии и трансплантации гемопоэтических стволовых клеток (ТГСК) в первой ремиссии. В последнее десятилетие получены новые данные, позволившие расшифровать некоторые механизмы лейкемогенеза при этой форме транслокации и приблизиться к пониманию причин высокой рефрактерности заболевания к применяемым химиопрепаратам. Наряду с сообщениями о возможной эффективности при данном варианте ОЛЛ ингибитора BCL-2 (венетоклакс) и аврора-киназы А (алисертиб) основные надежды связываются с применением современных схем клеточной иммунотерапии (различные варианты CAR-T) и моноклональных препаратов против антигенов опухолевых клеток CD19 и CD22 (блинатумомаб и инотузумаба озогамицин). До настоящего времени нет данных прямых сравнений эффективности этих методов между собой и общепринятого консенсуса оптимальной терапии. Неясно также, смогут ли эти методы заменить собой ТГСК или способны лишь увеличить безрецидивную выживаемость после нее. В настоящей работе мы приводим обзор литературных данных и собственное клиническое наблюдение мальчика 3 лет с данной формой лейкемии, не ответившего на 4-компонентную терапию индукции по протоколу ALL-MB 2015 и получившего терапию аутологичными CAR-T-лимфоцитами, специфичными к антигену CD19, с достижением первой МОБ (минимальная остаточная болезнь)-негативной ремиссии, сохранявшейся 11 мес, последующим МОБ-рецидивом с неуспешной попыткой терапии CD19-/CD22-специфичными аутологичными CAR-T-лимфоцитами с прогрессией заболевания до развернутого изолированного костномозгового рецидива, реиндукцией второй МОБ-негативной ремиссии на фоне применения инотузумаба озогамицина с последующим проведением аллогенной родственной ТГСК с сохранением полной молекулярной ремиссии в течение 16 мес после нее. Родители пациента дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях.

acute lymphoblastic leukemiachildrenhigh riskt(1719)(q21-q22p13)TCF3::HLFcell therapyALL-MB 2015 protocolCAR-T-therapy

острый лимфобластный лейкоздетивысокий рискt(1719)(q21-q22p13)TCF3::HLFклеточная терапияпротокол ALL-MB 2015CAR-T-терапия

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