Olga Streneva

Regional Children's Clinical Hospital No. 1

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АМ

А. М. Попов

National Research Center for Hematology Russian Academy of Medical Sciences

ЛГ

Л. Г. Фечина

Institute of Medical Cell Technologies

Grigory Tsaur

Regional Children's Clinical Hospital No. 1

Tatiana Verzhbitskaya

Regional Children's Clinical Hospital No. 1

Egor Shorikov

Moscow City Oncology Hospital №62

Olga Aleinikova

Belarusian Research Center For Pediatric Oncology and Hematology

Olga Khlebnikova

Regional Children's Clinical Hospital No. 1

Natalia Ponomareva

Russian Children's Clinical Hospital

Alexander Karachunskiy

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Anatoly Kustanovich

Hadassah Medical Center

Cooperative Institutions

Ministry of Health of the Russian Federation

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

Regional Children's Clinical Hospital No. 1

Institute of Medical Cell Technologies

National Research Center for Hematology Russian Academy of Medical Sciences

Pirogov Russian National Research Medical University

Russian Children's Clinical Hospital

Regional Children's Hospital No1

Belarusian Research Center For Pediatric Oncology and Hematology

Ural State Medical University

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Терапия Т-клеточного острого лимфобластного лейкоза у детей: опыт Российско-Белорусской кооперированной группы

G. R. Sharapova Юлия Васильевна Румянцева Э Г Бойченко Svetlana Lagoiko О. И. Быданов

T-cell acute lymphoblastic leukemia (T-ALL) is a tumor developing as a result of malignant transformation of precursor T-cells. Despite the fact that T-ALL is responsible for about 10-15% of all ALL cases in children, it is essential to separate T-ALL in a special subgroup, as a nosological entity by the tumor biology, poor clinical outcome and resistance to therapy. We analyze the results of treatment of 644 patients with T-ALL, registered in the data base of the Russian-Byelorussian Research Group over 24 years of its work. The initial characteristics of the patients, responses to therapy, prognostic factors, and efficacy of various therapeutic options are analyzed.

10.24287/1726-1708-2015-14-1-26-37

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ИССЛЕДОВАНИЕ СТРУКТУРЫ ХИМЕРНЫХ ГЕНОВ С УЧАСТИЕМ ГЕНА MLL ПРИ ОСТРЫХ ЛЕЙКОЗАХ У ДЕТЕЙ ПЕРВОГО ГОДА ЖИЗНИ

Гематология и трансфузиология (2014)

Цаур Григорий Анатольевич Claus Meyer А. М. Попов Olga Plekhanova Anatoly Kustanovich

Р е з ю м е. Целью данной работы являлось описание механизмов образования химерных генов с вовлечением гена MLL у детей первого года жизни, больных острыми лейкозами, у которых методом длинной инвертированной полимеразной цепной реакции (ДИ-ПЦР) в ДНК выявлена перестройка гена MLL. В исследование были включены 72 больных в возрасте от 1 дня до 11 мес, в том числе 52 больных острым лимфобластным лейкозом (ОЛЛ), 19 больных острым миелоидным лейкозом (ОМЛ), 1 больной острым недифференцированным лейкозом. При ОЛЛ наиболее частым (53,8%) химерным геном являлся MLL-AF4, реже выявлялись MLL-MLLT1 (23,1%), MLL-MLLT3 (13,5%), MLL-EPS15 (7,7%), MLL-AFF3 (1,9%). При ОМЛ самым часто выявляемым (36,8%) химерным геном был MLL-MLLT3, реже (26,3%) были найдены MLL-MLLT10, MLL-MLLT11 и MLL-MYO1F (по 10,5%), MLL-AF4, а также MLL-SEPT6 и MLL-SEPT9 (по 5,3%). Наиболее частой зоной разрыва в ДНК гена MLL при ОЛЛ являлся 11-й интрон, на долю которого приходилось 48,1% случаев, а при ОМЛ — это 9-й интрон (42,1%). Больные ОЛЛ, у которых точка разрыва располагалась в 11-м интроне, были младше всех остальных (p = 0,025). Не обнаружено связи между локализацией точек разрыва и полом больного, уровнем инициального лейкоцитоза и типом гена-партнера. Зоны разрыва в генах-партнерах MLL чаще всего затрагивали один или два интрона, за исключением генов AF4 и MLLT10, в которых зоны разрывов более протяженные. Самым частым механизмом образования химерных генов с участием MLL являлась реципрокная транслокация (73,6%), значительно реже — транс-сплайсинг (15,3%) или инсерции (11,1%). С помощью ДИ-ПЦР были найдены такие редкие гены-партнеры MLL, как AFF3, MYO1F, SEPT6, SEPT9, а также нетипичные локализации точек разрыва при наличии MLL-AF4: 7-й интрон гена MLL и 10-й интрон гена AF4, не выявляемые стандартной ПЦР с обратной транскрипцией. Таким образом, нами детально охарактеризована структура химерных генов с участием MLL в большой группе детей первого года жизни, больных острыми лейкозами. Ключевые слова : острый лейкоз; дети первого года жизни; перестройки гена MLL; полимеразная цепная реакция.

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MLL Gene Rearrangements in 174 Infants with Acute Leukemia.

Blood (2012)

Grigory Tsaur А. М. Попов Е. В. Флейшман Sokova Oi Anna Demina

Breakpoint

Gene rearrangement

10.1182/blood.v120.21.2537.2537

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Peg-Asparaginase Administration on Day 3 of Remission Induction Accelerates MRD Response in Children with B-Cell Precursor Acute Lymphoblastic Leukemia

Blood (2017)

А. М. Попов О. И. Быданов Julia Roumiantseva Svetlana Lagoiko Mikhail Belevtsev

Asparaginase

Acute lymphocytic leukemia

10.1182/blood.v130.suppl_1.3983.3983

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A Single Dose of PEG-Asparaginase at the Beginning of Induction Not Only Accelerates MRD Clearance but Also Improves Long-Term Outcome in Children with B-Lineage ALL

Cancers (2023)

А. М. Попов Günter Henze Julia Roumiantseva Oleh Bydanov Mikhail Belevtsev

This report presents the results of the assessment of MRD response by multicolor flow cytometry (MFC) with regard to the randomized use of pegylated asparaginase (PEG). In this study, PEG was randomly administered at a dose of 1000 U/m2 on day 3 of induction therapy in children with B-lineage ALL. Methods. Conventional induction therapy consisted of dexamethasone, vincristine, and daunorubicin. MRD data was available in 502 patients who were randomized at the start of induction therapy, standard-risk (SR) patients into three (conventional induction without PEG, induction with additional PEG and with PEG but without daunorubicin) and intermediate-risk (ImR) patients into two groups (with additional PEG and without PEG). Results. The single administration of PEG resulted in a significantly higher proportion of rapid responders, in SR patients even when no anthracyclines were used for induction. In the SR group, the event-free survival of the MFC-MRD fast responders was similar in the PEG− and PEG+ arms (92.0 ± 3.1% vs. 96.2 ± 1.5%, respectively), and the same unfavorable trend was observed for MFC-MRD slow responders (57.5 ± 12.3% vs. 66.7 ± 15.7%, respectively). Results were similar in ImR patients: (94.3 ± 3.2% vs. 95.1 ± 2.4%, for fast responders and 63.3 ± 7.6% vs. 78.1 ± 7.9%, for slow responders in PEG− and PEG+ arms, respectively). However, there is a large difference between the proportion of MFC-MRD slow responders in the PEG− and PEG+ groups (18.3% vs. 5.2% for the SR group and 44.2% vs. 25.0% for the ImR group). Conclusions. Therefore, early use of PEG-ASP not only leads to an accelerated reduction of blasts, but also to an excellent outcome in a significantly larger proportion of patients in both risk groups.

Daunorubicin

Asparaginase

10.3390/cancers15235547

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One-point flow cytometric MRD measurement to identify children with excellent outcome after intermediate-risk BCP-ALL: results of the ALL-MB 2008 study

Journal of Cancer Research and Clinical Oncology (2022)

А. М. Попов Guenter Henze Julia Roumiantseva Oleg Budanov Mikhail Belevtsev

Minimal Residual Disease

Intensity

Hematology

10.1007/s00432-022-04378-3

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Treatment of acute lymphoblastic leukemia in adolescents and young adults: the experience of the Moscow–Berlin

Russian Journal of Pediatric Hematology and Oncology (2016)

А. V. Pshonkin Yu. V. Rumyantseva Dmitry Litvinov А Ф Карелин E. G. Boychenko

One of the main risk-factors of acute lymphoblastic leukemia (ALL) is age. The most favorable age group is children from 2 to 9 years old, and the adolescents and young adults have the worst prognosis. Treatment of ALL at adolescents and young adults is a unique problem of modern hematology now. This work presents the analysis of 368 cases of patients with primary ALL 15–18 years old, which were registered in the database of Russian-Belarussian group from April 2002 to November 2014. The aim of the analysis was the estimation of effectiveness of different generations of protocol for adolescents and prognostic significance of different factors to reveal the ways of future therapy optimizing in this age group. Event-free survival of adolescents 15–18 years old according our study was 56 ± 5 % in ALL-MB-2002 study and 57 ± 6 % in ALL-MB-2008 study. We did not received any differences in survival based on immunophenotype of blast cells. But the risk group analysis showed the worst results at patients with ALL from pre-B-precursor cells of high risk. No difference was revealed according the gender. One of the general problems remains high toxicity of therapy at patients of this age group. Treatment related mortality (TRM) was 13.2 and 12 % at ALL-MB-2002 and ALL-MB-2008 accordingly. Main cause of deaths remains infection.

Immunophenotyping

Hematology

Age groups

10.17650/2311-1267-2016-3-1-35-43

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Острые лейкозы у детей первого года жизни: прогностическое значение локализации точки разрыва в ДНК гена mll

Клиническая онкогематология. Фундаментальные исследования и клиническая практика (2016)

Цаур Григорий Анатольевич Katharina Meier Т О Ригер Anatoly Kustanovich Е. В. Флейшман

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Flow cytometric minimal residual disease monitoring in children with acute lymphoblastic leukemia treated by regimens with reduced intensity

Oncohematology (2015)

А. М. Попов Y. Yu. Verzhbitskaya Grigory Tsaur Alexander Solodovnikov О. R. Arakaev

191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study. Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188), 36 (n = 191), and 85 (n = 187) of remission induction. Minimal residual disease (MRD) was assessed by 6–10-color flow cytometry. Flow cytometry data at day 15 allowed distinguishing three patients groups with significantly different outcome (p ˂ 0.0001): 35.64 % patients with MRD < 0.1 % represented 5-year event-free survival (EFS) of 100 %; 48.40 % cases with 0.1 % ≤ MRD< 10 % had EFS 84.6 ± 4.2 %; 15.96 % patients with very high MRD (≥ 10 %) belonged to group with poor outcome (EFS 56.7 ± 9.0 %). At the end of remission induction (day 36) 36 children (18.85 %) with MRD higher than 0.1 % had significantly worse outcome compared to remaining ones (EFS 49.4 ± 9.0 and 93.5 ± 2.1 % respectively; p ˂ 0.0001). From a clinical standpoint it is relevant to evaluate both low-risk and high-risk criteria. Multivariate analysis showed that day 15 MRD data is better for low-risk patients definition while end-induction MRD is the strongest unfavorable prognostic factor.

Minimal Residual Disease

10.17650/1818-8346-2015-10-4-44-55

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Цитогенетическая и молекулярно-генетическая характеристики острых лейкозов у детей первого года жизни

Клиническая онкогематология. Фундаментальные исследования и клиническая практика (2011)

Grigory Tsaur Е. В. Флейшман А. М. Попов Sokova Oi Olga Aleinikova

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