Olga Khlebnikova

Regional Children's Clinical Hospital No. 1

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Olga Streneva

Regional Children's Clinical Hospital No. 1

АМ

А. М. Попов

National Research Center for Hematology Russian Academy of Medical Sciences

Grigory Tsaur

Regional Children's Clinical Hospital No. 1

ЛГ

Л. Г. Фечина

Institute of Medical Cell Technologies

Tatiana Verzhbitskaya

Regional Children's Clinical Hospital No. 1

Alexander Karachunskiy

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

Olga Aleinikova

Belarusian Research Center For Pediatric Oncology and Hematology

Natalia Miakova

National Research Center for Hematology Russian Academy of Medical Sciences

Natalia Ponomareva

Russian Children's Clinical Hospital

Julia Roumiantseva

National Research Center for Hematology Russian Academy of Medical Sciences

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

National Research Center for Hematology Russian Academy of Medical Sciences

Russian Children's Clinical Hospital

Pirogov Russian National Research Medical University

Institute of Medical Cell Technologies

Belarusian Research Center For Pediatric Oncology and Hematology

Regional Children's Hospital No1

City Clinical Hospital No 31

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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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Citations (2)

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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Therapy of Advanced-stage Mature B-cell Lymphoma and Leukemia in Children and Adolescents With Rituximab and Reduced Intensity Induction Chemotherapy (B-NHL 2004M Protocol)

Journal of Pediatric Hematology/Oncology (2013)

Elena Samochatova Alexey Maschan Larisa Shelikhova N. V. Myakova М. Б. Белогурова

Pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs) are highly aggressive malignant tumors that are curable with chemotherapy (ChT). High-dose methotrexate (MTX) is considered indispensable for successful treatment, but this therapy frequently induces severe mucositis and infectious complications, especially in induction, which can cause treatment failure. A prospective multicenter trial of combined immunochemotherapy for advanced-stage B-NHL with rituximab and the modified NHL-BFM-90 protocol was conducted. The major differences from the original protocol were a decrease in the dose of MTX from 5000 to 1000 mg/m/24 h in the first 2 ChT blocks and the addition of rituximab at 375 mg/m to each of the first 4 blocks of ChT. Eighty-three newly diagnosed patients with a median age of 8.84 years with Burkitt lymphoma/leukemia and diffuse large B-cell lymphomas stage III to IV were included. Four patients died during induction ChT due to tumor lysis syndrome and infection. Two additional patients died subsequently due to tumor resistance. Complete remission was achieved in 77 (92.8%) patients; 2 patients relapsed at 1 and 3 months, and 2 developed secondary malignancies at 1 and 6.5 years, respectively, after the completion of therapy. The overall survival probability was 82%±8% with a median follow-up of 65.2 months. Combined therapy with rituximab and intensive ChT with a reduced MTX dose of 1 g/m in the 2 induction courses was feasible and produced high cure rates in patients with pediatric advanced-stage mature B-NHL.

Mucositis

Induction chemotherapy

10.1097/mph.0b013e31829d4900

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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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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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Эпигенетическая терапия — важная составляющая в лечении детей, больных острым миелоидным лейкозом

Клиническая онкогематология. Фундаментальные исследования и клиническая практика (2011)

А. В. Попа Е. В. Горохова Е. В. Флейшман Sokova Oi И. Н. Серебрякова

The results of pediatric AML are not good that is why we try to find new abilities of treatment besides knowing chemotherapy. We propose combination of epigenetic and chemotherapy is able to improve the treatment results in this group of patients. From 1991 to 2010 3 consecutive studies with 157 children enrolled were conducted, age 3 mo to 17 years, median age is 8.5 ± 0.39 years. In the protocol AML BFM 87 54 pts (m 35 (64.8 %), f 19 (35.2 %) were enrolled, in study NII DOG AML 2002 52 pts (m 26 (51 %) and f 25 (49 %). The protocol NII DOG AML 2007 was based on the combination of chemotherapy and epigenetic therapy consisting of valproic acid and all trans retinoic acid (ATRA). There were 52 pts were included in that study (m 31 (59.6 %) and f 21 (40.4 %). The remission rate was 43 (76.9 %) pts in protocol AML BFM 87, 43 (84.3 %) in protocol NII DOG AML 2002 and 48 (92.3 %) in protocol NII DOG AML 2007, p = 0.17. Complete remission achievement was higher in pts from high risk cohort who were treated by protocol NII DOG AML 2007 21 (91.3 %) than by AML BFM 87 9 (69.2 %) and NII DOG AML 2002 9 (74.2 %), p < 0.0001. Despite the absence of significant difference of EFS and DFS between pts stratified in different risk groups (EFS for standard, intermedium and high p = 0.8, p = 0.5 and p = 0.16; DFS p = 0.57, p = 0.4 and p = 0.19) EFS and DFS were higher in NII DOG AML 2007 study for all risk groups. Thus, the combination of chemotherapy with epigenetic drugs allows to achieve more complete remissions in intermedium and high risk groups of pts and higher survival. These results allow us to continue the study with histone deacetylating inhibitors and make a new protocol with demethylation drugs. Key words: acute myeloid leukemia, epigenetic therapy, chemotherapy, treatment, histone deacetylating inhibitors, valproic acid, all trans retinoic acid (ATRA).

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

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

Minimal Residual Disease

Intensity

Acute lymphocytic leukemia

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Relapse Prediction By Flow Cytometric Minimal Residual Disease Assessment in Infants with Acute Lymphoblastic Leukemia