A reproducible strategy for analysis of minimal residual disease measured by Standardized multiparametric flow cytometry in b acute lymphoblastic leukemia

Palao, Héctor Sarmiento; Tarín, Fabián; Martirena, Fernanda; Barragán, Eva; Such, Esperanza; Sempere, Amparo; Tasso, M.; Manresa, Pablo Manresa; López, Francisco

doi:10.1002/cyto.b.21720

Cited by 6 publications

(3 citation statements)

References 7 publications

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“…While HG was not detected in 31 (38.8%) patients, HG was detected in 49 (61.2%) patients. The median HG value in the HG (+) group was found five (Chantepie et al, 2013;Chantepie et al, 2016;D'Arena et al, 2001;Doki et al, 2015;Greipp et al, 2005;Lúcio et al, 1999;McKenna et al, 2001;McKenna et al, 2004;Moreno-Madrid et al, 2008;Muehleck et al, 1983;Palumbo et al, 2015;Palumbo & Anderson, 2011;Sarmiento Palao et al, 2019;Sevilla et al, 2010). The demographic and clinical characteristics of these two groups are summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…While the ratio of HG decreases with age, it is known that there is no difference between women and men in terms of HG ratio (Lúcio et al, 1999;McKenna et al, 2001). HGs after chemotherapy have been proven to be successful in predicting early relapse in some diseases such as acute myeloid leukemia (AML) and Acute lymphoblastic leukemia (ALL) (Chantepie et al, 2016;Sarmiento Palao et al, 2019). In addition, in a few recent studies it has been shown that the increased HG level that was observed after allogeneic stem cell transplantion can be used as a prognostic marker in various hematological malignancies (Doki et al, 2015;Honebrink et al, 2012).…”

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confidence: 99%

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Prognostic significance of hematogone presence after autologous stem cell transplantation in patients with multiple myeloma

Göçer

Kurtoğlu

2021

Cytometry Part B Clinical

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Background: Morphologically and immunophenotypically, the number of B-lymphocyte progenitor cells, so-called hematogones increases after chemotherapy and allogeneic stem cell transplantions. It is thought that hematogones can be used as a prognostic marker in these patients. It is aimed to determine the prognostic significance and factors affecting the development of hematogones, which can be seen after autologous stem cell transplantation in multiple myeloma (MM) patients.Methods: This retrospective and single center study includes 80 patients who underwent autologous stem cell transplantation with the diagnosis of MM in our clinic between January 2013 and December 2019. The primary endpoint of the study was the relationship between the presence and rate of hematogone (HG) and progression free survival (PFS) and overall survival (OS). The secondary endpoint was to identify the factors affecting the development of HG.Results: HG was detected in 61.2% of the patients. There was a moderate and positive linear correlation between the amount of stem cells given and HG ratio (r = 0.387, p = 0.000). PFS and OS were significantly shorter in the group with HG (p = 0.000 and p = 0.012).Conclusions: HG positivity after autologous stem cell transplantation was found to be an independent prognostic marker for PFS and OS in patients with MM. There is a positive relationship between the amount of stem cells used during transplantation and the ratio of HG. As the amount of stem cells increases, the ratio of HG increases and when the ratio of HG increases, PFS and OS become shorter.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Prognostic significance of hematogone presence after autologous stem cell transplantation in patients with multiple myeloma

Göçer

Kurtoğlu

2021

Cytometry Part B Clinical

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“…Marker profile comparisons are achieved through various combinations of monoclonal antibodies against surface, cytoplasmic, or nuclear leukocyte antigens. A second approach is represented by the so-called "different from normal (DFN)" analysis, which identifies leukemic blasts by recognizing immunophenotypic changes with respect to a normal counterpart population (either hematopoietic progenitors of similar lineage and maturational stage) through the evaluation of antigenic pattern expressions [25,26]. At present, the most commonly used MFC panels comprise 6-8 monoclonal antibody (MoAb) combinations.…”

Section: Multi-parametric Flow Cytometry Analysismentioning

confidence: 99%

Minimal residual disease in acute lymphoblastic leukemia: technical aspects and implications for clinical interpretation

Kim

2020

Blood Res

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Minimal residual disease (MRD) monitoring has proven to be one of the fundamental independent prognostic factors for patients with acute lymphoblastic leukemia (ALL). Sequential monitoring of MRD using sensitive and specific methods, such as real-time quantitative polymerase chain reaction (qPCR) or flow cytometry (FCM), has improved the assessment of treatment response and is currently used for therapeutic stratification and early detection. Although both FCM and qPCR yield highly consistent results with sensitivities of 10-4 , each method has several limitations. For example, qPCR is time-consuming and laborious: designing primers that correspond to the immunoglobulin (IG) and T-cell receptor (TCR) gene rearrangements at diagnosis can take 3-4 weeks. In addition, the evolution of additional clones beyond the first or index clone during therapy cannot be detected, which might lead to false-negative results. FCM requires experienced technicians and sometimes does not achieve a sensitivity of 10-4. Accordingly, a next generation sequencing (NGS)-based method has been developed in an attempt to overcome these limitations. With the advent of high-throughput NGS technologies, a more in-depth analysis of IG and/or TCR gene rearrangements is now within reach, which impacts all applications of IG/TR analysis. However, standardization, quality control, and validation of this new technology are warranted prior to its incorporation into routine practice.

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A High‐Sensitivity 10‐Color Flow Cytometric Minimal Residual Disease Assay in B‐Lymphoblastic Leukemia/Lymphoma Can Easily Achieve the Sensitivity of 2‐in‐10⁶and Is Superior to Standard Minimal Residual Disease Assay: A Study of 622 Patients

Tembhare

Subramanian

Ghogale

et al. 2019

Cytometry Part B Clinical

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BackgroundFlow‐cytometric minimal residual disease (FC‐MRD) monitoring is a well‐established risk‐stratification factor in B‐lymphoblastic leukemia/lymphoma (‐B‐ALL) and is being considered as a basis for deintensification or escalation in treatment protocols. However, currently practiced standard FC‐MRD has limited sensitivity (up to 0.01%) and higher false MRD‐negative rate. Hence, a highly sensitive, widely applicable, and easily reproducible FC‐MRD assay is needed, which can provide a reliable basis for therapeutic modifications.MethodsA 10‐color high‐event analysis FC‐MRD assay was studied for the evaluation of MRD status at postinduction, (PI; day‐35), postconsolidation, (PC; day‐78), and subsequent follow‐up time‐points (SFU) in bone marrow samples from pediatric B‐ALL.ResultsOne‐thousand MRD samples (PI‐62.2%; PC‐26.5%; and SFU‐11.3%) from 622 childhood B‐ALL patients were studied. High‐event analysis was performed with median 4,452,000 events (range, 839,000 to 8,866,000 events) and >4 million events in 71% samples. MRD was measurable in 43.2% of PI‐samples, in 29.4% PC‐samples, and in 32.7% SFU‐samples. To simulate comparison with standard FC‐MRD, we reanalyzed MRD results gating only first 500,000 and first 1000,000 events in 122 PI‐MRD positive samples with MRD levels <0.02%. Of these samples gated for 500,000 events and 1000,000 events, 32% and 21.3% were found to be falsely MRD‐negative, respectively.ConclusionsWe report an easily reproducible high‐sensitivity 10‐color FC‐MRD assay with the sensitivity of 2‐in‐106 (0.0002%). It allowed the detection of low‐level MRD in samples, which could have been reported negative using the standard FC‐MRD with limited event analysis. Thus, this high‐sensitivity MRD‐methodology can provide a reliable basis for therapeutic modifications in B‐ALL. © 2019 International Clinical Cytometry Society

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A reproducible strategy for analysis of minimal residual disease measured by Standardized multiparametric flow cytometry in b acute lymphoblastic leukemia

Cited by 6 publications

References 7 publications

Prognostic significance of hematogone presence after autologous stem cell transplantation in patients with multiple myeloma

Prognostic significance of hematogone presence after autologous stem cell transplantation in patients with multiple myeloma

Minimal residual disease in acute lymphoblastic leukemia: technical aspects and implications for clinical interpretation

A High‐Sensitivity 10‐Color Flow Cytometric Minimal Residual Disease Assay in B‐Lymphoblastic Leukemia/Lymphoma Can Easily Achieve the Sensitivity of 2‐in‐10⁶and Is Superior to Standard Minimal Residual Disease Assay: A Study of 622 Patients

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A reproducible strategy for analysis of minimal residual disease measured by Standardized multiparametric flow cytometry in b acute lymphoblastic leukemia

Cited by 6 publications

References 7 publications

Prognostic significance of hematogone presence after autologous stem cell transplantation in patients with multiple myeloma

Prognostic significance of hematogone presence after autologous stem cell transplantation in patients with multiple myeloma

Minimal residual disease in acute lymphoblastic leukemia: technical aspects and implications for clinical interpretation

A High‐Sensitivity 10‐Color Flow Cytometric Minimal Residual Disease Assay in B‐Lymphoblastic Leukemia/Lymphoma Can Easily Achieve the Sensitivity of 2‐in‐106and Is Superior to Standard Minimal Residual Disease Assay: A Study of 622 Patients

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A High‐Sensitivity 10‐Color Flow Cytometric Minimal Residual Disease Assay in B‐Lymphoblastic Leukemia/Lymphoma Can Easily Achieve the Sensitivity of 2‐in‐10⁶and Is Superior to Standard Minimal Residual Disease Assay: A Study of 622 Patients