Flow cytometric and cytomorphological definition of remission achievement in children with B-lineage acute lymphoblastic leukemia

A. M. Popov; Попов А. М.; G. A. Tsaur; Цаур Г. А.; Yu. V. Rumiantseva; Румянцева Ю. В.; O. I. Bydanov; Быданов О. И.; T. Yu. Verzhbitskaya; Вержбицкая Т. Ю.; L. V. Movchan; Мовчан Л. В.; E. V. Mikhailova; Михайлова Е. В.; O. I. Illarionova; Илларионова О. И.; M. V. Belevtsev; Белевцев М. В.; S. N. Lagoyko; Лагойко С. Н.; L. I. Zharikova; Жарикова Л. И.; Zh. V. Permikin; Пермикин Ж. В.; N. V. Myakova; Мякова Н. В.; D. V. Litvinov; Литвинов Д. В.; O. P. Khlebnikova; Хлебникова О. П.; O. V. Streneva; Стренева О. В.; O. R. Arakaev; Аракаев О. Р.; E. A. Stolyarova; Столярова Е. А.; L. A. Khachatryan; Хачатрян Л. А.; N. I. Ponomareva; Пономарева Н. И.; O. V. Aleinikova; Алейникова О. В.; L. G. Fechina; Фечина Л. Г.; G. A. Novichkova; Новичкова Г. А.; A. I. Karachunskiy; Карачунский А. И.

doi:10.24287/1726-1708-2023-22-4-79-89

Flow cytometric and cytomorphological definition of remission achievement in children with B-lineage acute lymphoblastic leukemia

Authors: Popov A.M.¹, Tsaur G.A.²^,3^,4, Rumiantseva Y.V.¹^,5, Bydanov O.I.¹, Verzhbitskaya T.Y.²^,3, Movchan L.V.⁶, Mikhailova E.V.¹, Illarionova O.I.¹, Belevtsev M.V.⁶, Lagoyko S.N.¹, Zharikova L.I.¹^,5, Permikin Z.V.²^,4, Myakova N.V.¹, Litvinov D.V.¹^,5, Khlebnikova O.P.², Streneva O.V.²^,3, Arakaev O.R.², Stolyarova E.A.⁶, Khachatryan L.A.¹, Ponomareva N.I.⁷, Aleinikova O.V.¹, Fechina L.G.²^,3, Novichkova G.A.¹, Karachunskiy A.I.¹^,5
Affiliations:
1. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
2. Regional Children's Clinical Hospital
3. Institute of Medical Cell Technologies
4. Ural State Medical University of Ministry of Healthcare of the Russian Federation
5. N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation
6. Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
7. Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation
Issue: Vol 22, No 4 (2023)
Pages: 79-89
Section: ORIGINAL ARTICLES
Submitted: 05.01.2024
Accepted: 05.01.2024
Published: 20.12.2023
URL: https://hemoncim.com/jour/article/view/803
DOI: https://doi.org/10.24287/1726-1708-2023-22-4-79-89
ID: 803

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Abstract

The achievement of remission at the end of induction (EOI) chemotherapy in patients with acute lymphoblastic leukemia (ALL) is the key parameter of treatment effectiveness evaluation. The aim of the study – defining complete remission by multicolor flow cytometry (MFC) and bone marrow (BM) cytomorphology (CM) at the EOI chemotherapy in children with B-lineage ALL. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study included patients of “ALL-MB 2008” and “ALL-MB 2015” trials for whom minimal residual disease (MRD) was evaluated by MFC at the EOI simultaneously with CM BM investigation. Less than 5% blasts in BM and MRD < 1% were established as the remission achievement criteria for CM and MFC respectively. The study group included 1498 children aged from 1 to 18 years (median age was 4 years and 11 months) with B-cell precursor ALL. The overall concordance of MFC and CM was found to be 96.1% (1440 of 1498 patients). In 36 (2.4%) children with MRD ≥ 1%, M1 BM status was observed. In contrast, in 22 (1.5%) patients with M2/M3 BM status by CM, MRD value was below 1%. Treatment outcome was analyzed in 522 patients of “ALL-MB 2008” trial. Children with M2/M3 BM, as well as with MRD ≥ 1% demonstrated dramatically inferior outcome, in comparison to those who achieved remission. The presence of at least one of the mentioned criteria (M2/M3 status by CM or MRD ≥ 1% by MFC) defined a group of 23 (4.4%) patients with very low event-free survival (34.9%, standard error 11.0%) and very high cumulative incidence of relapse (56.4%, standard error 12.0%). For the evaluation of remission achievement, MFC and CM should be applied simultaneously at the EOI. High leukemic burden found by any of these methods is the clear definition of induction failure. MRD detection at the EOI should be implemented in any modern treatment protocol as an obligatory stage of treatment response monitoring and final risk group stratification. Considering the crucial importance of the MRD detection results, this study must be performed only in the reference laboratories of the study groups.

Keywords

acute lymphoblastic leukemia, remission, flow cytometry, minimal residual disease

About the authors

A. M. Popov

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: uralcytometry@gmail.com
ORCID iD: 0000-0002-0889-6986

Alexander M. Popov, Cand. Med. Sci., Head of Leukemia Immunophenotyping Laboratory

1 Samory Mashela St., Moscow 117997

Russian Federation

G. A. Tsaur

Regional Children's Clinical Hospital;
Institute of Medical Cell Technologies;
Ural State Medical University of Ministry of Healthcare of the Russian Federation

Yekaterinburg

Russian Federation

Yu. V. Rumiantseva

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation;
N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-9670-3728

Moscow

Russian Federation

O. I. Bydanov

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0003-3232-2322

Moscow

Russian Federation

T. Yu. Verzhbitskaya

Regional Children's Clinical Hospital;
Institute of Medical Cell Technologies

ORCID iD: 0000-0001-9329-1828

Yekaterinburg

Russian Federation

L. V. Movchan

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Minsk

Belarus

E. V. Mikhailova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-3450-0498

Moscow

Russian Federation

O. I. Illarionova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

Moscow

Russian Federation

M. V. Belevtsev

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Minsk

Belarus

S. N. Lagoyko

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-3793-104X

Moscow

Russian Federation

L. I. Zharikova

ORCID iD: 0000-0002-1105-8676

Moscow

Russian Federation

Zh. V. Permikin

Regional Children's Clinical Hospital;
Ural State Medical University of Ministry of Healthcare of the Russian Federation

Yekaterinburg

Russian Federation

N. V. Myakova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0002-4779-1896

Moscow

Russian Federation

D. V. Litvinov

ORCID iD: 0000-0002-7461-0050

Moscow

Russian Federation

O. P. Khlebnikova

Regional Children's Clinical Hospital

Yekaterinburg

Russian Federation

O. V. Streneva

Regional Children's Clinical Hospital;
Institute of Medical Cell Technologies

Yekaterinburg

Russian Federation

O. R. Arakaev

Regional Children's Clinical Hospital

Yekaterinburg

Russian Federation

E. A. Stolyarova

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Minsk

Belarus

L. A. Khachatryan

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation

ORCID iD: 0000-0001-7265-0414

Moscow

Russian Federation

N. I. Ponomareva

Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation

Moscow

Russian Federation