Minimal residual disease monitoring in B-lineage acute lymphoblastic leukemia using flow cytometry. Guidelines of the Russian-Belarusian multicenter group for pediatric acute leukemia studies

Popov, A. M.; Mikhailova, E. V.; Verzhbitskaya, T. Yu.; Movchan, L. V.; Permikin, Zh. V.; Shman, T. V.; Karachunskiy, A. I.; Novichkova, G. A.

doi:10.24287/1726-1708-2023-22-3-199-209

Cited by 4 publications

(2 citation statements)

References 37 publications

(33 reference statements)

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“…Based on the cytogenetic data, patients were classified into low (high hyperdiploidy (HeH) and translocation t(12;21)(p13;q22)/ ETV6 :: RUNX1 13 ) and intermediate (all others) cytogenetic risk groups 13 . MRD was evaluated using a 6–9 color MFC in three laboratories using a well‐harmonized approach 15,16 . All laboratories use the same MFC methodology based on standard analyzes and had participated in the AIEOP‐BFM‐QA system 17 and group‐internal proficiency tests 15 .…”

Section: Methodsmentioning

confidence: 99%

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Flow cytometric minimal residual disease measurement accounting for cytogenetics in children with non‐high‐risk acute lymphoblastic leukemia treated according to the ALL‐MB 2008 protocol

Popov,

Henze,

Tsaur

et al. 2024

Cancer Medicine

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BackgroundQuantitative measurement of minimal residual disease (MRD) is the “gold standard” for estimating the response to therapy in childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). Nevertheless, the speed of the MRD response differs for different cytogenetic subgroups. Here we present results of MRD measurement in children with BCP‐ALL, in terms of genetic subgroups with relation to clinically defined risk groups.MethodsA total of 485 children with non‐high‐risk BCP‐ALL with available cytogenetic data and MRD studied at the end‐of‐induction (EOI) by multicolor flow cytometry (MFC) were included. All patients were treated with standard‐risk (SR) of intermediate‐risk (ImR) regimens of “ALL‐MB 2008” reduced‐intensity protocol.Results and DiscussionAmong all study group patients, 203 were found to have low‐risk cytogenetics (ETV6::RUNX1 or high hyperdiploidy), while remaining 282 children were classified in intermediate cytogenetic risk group. For the patients with favorable and intermediate risk cytogenetics, the most significant thresholds for MFC‐MRD values were different: 0.03% and 0.04% respectively. Nevertheless, the most meaningful thresholds were different for clinically defined SR and ImR groups. For the SR group, irrespective to presence/absence of favorable genetic lesions, MFC‐MRD threshold of 0.1% was the most clinically valuable, although for ImR group the most informative thresholds were different in patients from low‐(0.03%) and intermediate (0.01%) cytogenetic risk groups.ConclusionOur data show that combining clinical risk factors with MFC‐MRD measurement is the most useful tool for risk group stratification of children with BCP‐ALL in the reduced‐intensity protocols. However, this algorithm can be supplemented with cytogenetic data for part of the ImR group.

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Section: Methodsmentioning

confidence: 99%

“… 13 MRD was evaluated using a 6–9 color MFC in three laboratories using a well‐harmonized approach. 15 , 16 All laboratories use the same MFC methodology based on standard analyzes and had participated in the AIEOP‐BFM‐QA system 17 and group‐internal proficiency tests. 15 MRD negativity was defined as <0.01%.…”

Section: Methodsmentioning

confidence: 99%

Flow cytometric minimal residual disease measurement accounting for cytogenetics in children with non‐high‐risk acute lymphoblastic leukemia treated according to the ALL‐MB 2008 protocol

Popov,

Henze,

Tsaur

et al. 2024

Cancer Medicine

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Guidelines for the use of flow cell sorting in diagnosis and monitoring of acute leukemia

Semchenkova,

Illarionova,

Demina

et al. 2023

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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Flow cell sorting is an advanced laboratory technique that combines the analytical capabilities of flow cytometry with the ability to isolate pure cell populations from heterogeneous samples. It has tremendous potential both for fundamental research and laboratory diagnosis. For example, the combination of cell sorting and molecular genetic studies can be used to clarify ambiguous results of acute leukemia immunophenotyping obtained both at diagnosis and during minimal residual disease monitoring. These guidelines are based on years of experience in incorporating cell sorting into the diagnostic and monitoring processes at the Leukemia Immunophenotyping Laboratory of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. They include methods used for the confirmation of flow cytometry data depending on the type of leukemia, the stage of a flow cytometry assay and previous therapy. They also describe cell sorting algorithms for disease diagnosis and the specifics of sample preparation for cell sorting in different molecular genetic studies.

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

Popov,

Tsaur,

Rumiantseva

et al. 2023

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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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.

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Minimal residual disease monitoring in B-lineage acute lymphoblastic leukemia using flow cytometry. Guidelines of the Russian-Belarusian multicenter group for pediatric acute leukemia studies

Cited by 4 publications

References 37 publications

Flow cytometric minimal residual disease measurement accounting for cytogenetics in children with non‐high‐risk acute lymphoblastic leukemia treated according to the ALL‐MB 2008 protocol

Flow cytometric minimal residual disease measurement accounting for cytogenetics in children with non‐high‐risk acute lymphoblastic leukemia treated according to the ALL‐MB 2008 protocol

Guidelines for the use of flow cell sorting in diagnosis and monitoring of acute leukemia

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

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