Standardization of Flow Cytometric Minimal Residual Disease Monitoring in Children With B-Cell Precursor Acute Lymphoblastic Leukemia. Russia–belarus Multicenter Group Experience

Popov, Alexander; Belevtsev, Mikhail; Боякова, Е. В.; Вержбицкая, Т. Ю.; Movchan, Liudmila; Fadeeva, Maria; Пащенко, А. Б.; Savitskii, V. P.; Левадный, А. А.; Tsaur, Grigory; Kashpor, Svetlana; Плясунова, С. А.; Fechina, Larisa; Алейникова, О. В.; Карачунский, А. И.

doi:10.17650/1818-8346-2016-11-4-64-73

Cited by 28 publications

(34 citation statements)

References 21 publications

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“…Therefore, CD19(À) BCPs remain unobserved because MRD detection is performed among CD19(+) cells. 19 In MRD assessment within CD19(+) cells, leukaemic cells can appear in 'empty spaces'regions defined on dot plots that usually contain no cells in control BM samples (Fig 6A). The significance of CD19(À) BCPs increases when CD19 needs to be replaced by another pan-B-cell marker, 40 i.e., for MFC-MRD monitoring in patients after CD19-directed therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Multicolor flow cytometry based MRD was assessed as described previously. 19 MFC (8-11 colours) was performed on three-laser fluorescence-activated cell sorting [FACSCanto II, Becton and Dickinson, (BD) NJ, USA], Navios (Beckman Coulter, Indianapolis IN, USA) and CytoFLEX (Beckman Coulter) flow cytometers. EuroFlow guidelines for machine performance monitoring were used.…”

Section: Mfc-mrd Studiesmentioning

confidence: 99%

“…In B-lineage ALL patients treated with chemotherapy, MFC-based detection of residual leukaemic cells is performed among CD19(+) cells. 18,19 With regard to CD19-directed therapy, the standard algorithm is limited by possible partial or complete elimination of the surface CD19. 15 Therefore, alternative pan-B-cell markers must be used for B-lineage compartment restriction, for example, CD22, CD24, 20 or intracellular (i)CD79a, which are generally detectable on blasts of B-lineage ALL.…”

Section: Introductionmentioning

confidence: 99%

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Relative expansion of CD19‐negative very‐early normal B‐cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR‐T cell therapy: implications for flow cytometric detection of minimal residual disease

et al. 2021

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CD19-directed treatment in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) frequently leads to the downmodulation of targeted antigens. As multicolour flow cytometry (MFC) application for minimal/measurable residual disease (MRD) assessment in BCP-ALL is based on B-cell compartment study, CD19 loss could hamper MFC-MRD monitoring after blinatumomab or chimeric antigen receptor T-cell (CAR-T) therapy. The use of other antigens (CD22, CD10, CD79a, etc.) as B-lineage gating markers allows the identification of CD19-negative leukaemia, but it could also lead to misidentification of normal very-early CD19-negative BCPs as tumour blasts. In the current study, we summarized the results of the investigation of CD19-negative normal BCPs in 106 children with BCP-ALL who underwent CD19 targeting (blinatumomab, n = 64; CAR-T, n = 25; or both, n = 17). It was found that normal CD19-negative BCPs could be found in bone marrow after CD19-directed treatment more frequently than in healthy donors and children with BCP-ALL during chemotherapy or after stem cell transplantation. Analysis of the antigen expression profile revealed that normal CD19-negative BCPs could be mixed up with residual leukaemic blasts, even in bioinformatic analyses of MFC data. The results of our study should help to investigate MFC-MRD more accurately in patients who have undergone CD19-targeted therapy, even in cases with normal CD19-negative BCP expansion.

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Section: Discussionmentioning

confidence: 99%

Section: Mfc-mrd Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Relative expansion of CD19‐negative very‐early normal B‐cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR‐T cell therapy: implications for flow cytometric detection of minimal residual disease

et al. 2021

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“…All patients underwent routine diagnostic immunophenotyping and MRD detection by 8-10-color flow cytometry according to the standard protocols of the Moscow-Berlin group (6,7).…”

mentioning

confidence: 99%

“…All patients underwent routine diagnostic immunophenotyping and MRD detection by eight- or ten-color flow cytometry according to the standard protocols of the Moscow-Berlin group. 6 , 7 During the study period MFC was performed on FACS Canto II, FACS Celesta (both from Becton Dickinson, BD; USA), CytoFlex and Navios (both from Beckman Coulter, BC; USA) flow cytometers. EuroFlow guidelines for machine performance monitoring were used.…”

mentioning

confidence: 99%

Immunophenotypic changes of leukemic blasts in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia who have been treated with blinatumomab

et al. 2020

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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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Standardization of Flow Cytometric Minimal Residual Disease Monitoring in Children With B-Cell Precursor Acute Lymphoblastic Leukemia. Russia–belarus Multicenter Group Experience

Cited by 28 publications

References 21 publications

Relative expansion of CD19‐negative very‐early normal B‐cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR‐T cell therapy: implications for flow cytometric detection of minimal residual disease

Relative expansion of CD19‐negative very‐early normal B‐cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR‐T cell therapy: implications for flow cytometric detection of minimal residual disease

Immunophenotypic changes of leukemic blasts in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia who have been treated with blinatumomab

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

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