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  1. Article: Updates on lymphoblastic leukemia/lymphoma classification and minimal/measurable residual disease analysis.

    Kovach, Alexandra E / Wood, Brent L

    Seminars in diagnostic pathology

    2023  Volume 40, Issue 6, Page(s) 457–471

    Abstract: Lymphoblastic leukemia/lymphoma (ALL/LBL), especially certain subtypes, continues to confer morbidity and mortality despite significant therapeutic advances. The pathologic classification of ALL/LBL, especially that of B-ALL, has recently substantially ... ...

    Abstract Lymphoblastic leukemia/lymphoma (ALL/LBL), especially certain subtypes, continues to confer morbidity and mortality despite significant therapeutic advances. The pathologic classification of ALL/LBL, especially that of B-ALL, has recently substantially expanded with the identification of several distinct and prognostically important genetic drivers. These discoveries are reflected in both current classification systems, the World Health Organization (WHO) 5th edition and the new International Consensus Classification (ICC). In this article, novel subtypes of B-ALL are reviewed, including DUX4, MEF2D and ZNF384-rearranged B-ALL; the rare pediatric entity B-ALL with TLF3::HLF, now added to the classifications, is discussed; updates to the category of B-ALL with BCR::ABL1-like features (Ph-like B-ALL) are summarized; and emerging genetic subtypes of T-ALL are presented. The second half of the article details current approaches to minimal/measurable residual disease (MRD) detection in B-ALL and T-ALL and presents anticipated challenges to current approaches in the burgeoning era of antigen-directed immunotherapy.
    MeSH term(s) Humans ; Child ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Lymphoma
    Language English
    Publishing date 2023-11-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 605834-6
    ISSN 1930-1111 ; 0740-2570
    ISSN (online) 1930-1111
    ISSN 0740-2570
    DOI 10.1053/j.semdp.2023.10.001
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  2. Article ; Online: Acute Myeloid Leukemia Minimal Residual Disease Detection: The Difference from Normal Approach.

    Wood, Brent L

    Current protocols in cytometry

    2020  Volume 93, Issue 1, Page(s) e73

    Abstract: The identification of residual leukemia following therapy, termed minimal or measurable residual disease (MRD), has emerged as one of the most important prognostic factors for patients with acute leukemia, including acute myeloid leukemia (AML). Flow ... ...

    Abstract The identification of residual leukemia following therapy, termed minimal or measurable residual disease (MRD), has emerged as one of the most important prognostic factors for patients with acute leukemia, including acute myeloid leukemia (AML). Flow cytometry is a preferred method for MRD detection due to its general applicability and the rapid results that it makes available. In this article, the basic protocol outlines a simple and efficient method for the labeling of hematopoietic cells from bone marrow or peripheral blood with a panel of monoclonal antibodies designed both to highlight patterns of normal maturation and allow identification of neoplastic hematopoietic progenitor populations with a high degree of sensitivity and specificity. The method was developed in a clinical laboratory setting for the diagnosis of myeloid stem cell disorders and neoplasms, and has been extensively validated both technically and clinically for the detection of MRD in AML. © 2020 The Authors. Basic Protocol: Staining and flow cytometry for AML minimal residual disease detection Support Protocol: Analysis and interpretation of data for AML minimal residual disease detection.
    MeSH term(s) Antibodies, Neoplasm/metabolism ; Cell Survival ; Flow Cytometry/methods ; Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cells/pathology ; Humans ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/pathology ; Leukocyte Common Antigens/metabolism ; Mutation/genetics ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/pathology ; Nuclear Proteins/genetics ; Staining and Labeling
    Chemical Substances Antibodies, Neoplasm ; Nuclear Proteins ; nucleophosmin (117896-08-9) ; Leukocyte Common Antigens (EC 3.1.3.48)
    Language English
    Publishing date 2020-04-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2179050-4
    ISSN 1934-9300 ; 1934-9297
    ISSN (online) 1934-9300
    ISSN 1934-9297
    DOI 10.1002/cpcy.73
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  3. Article ; Online: Principles of minimal residual disease detection for hematopoietic neoplasms by flow cytometry.

    Wood, Brent L

    Cytometry. Part B, Clinical cytometry

    2016  Volume 90, Issue 1, Page(s) 47–53

    Abstract: Flow cytometry has become an indispensible tool for the diagnosis and classification of hematopoietic neoplasms. The ability to rapidly distinguish cellular subpopulations via multiparametric assessment of quantitative differences in antigen expression ... ...

    Abstract Flow cytometry has become an indispensible tool for the diagnosis and classification of hematopoietic neoplasms. The ability to rapidly distinguish cellular subpopulations via multiparametric assessment of quantitative differences in antigen expression on single cells and enumerate the relative sizes of the resulting subpopulations is a key feature of the technology. More recently, these capabilities have been expanded to include the identification and enumeration of rare subpopulations within complex cellular mixtures, for example, blood or bone marrow, leading to the application for post-therapeutic monitoring or minimal residual disease detection. This review will briefly present the principles to be considered in the construction and use of flow cytometric assays for minimal residual disease detection including the use of informative antibody combinations, the impact of immunophenotypic instability, enumeration, assay sensitivity, and reproducibility.
    MeSH term(s) Antibodies/chemistry ; Antigens, CD/analysis ; Antigens, CD/genetics ; Antigens, CD/immunology ; Antineoplastic Agents/therapeutic use ; Bone Marrow Cells/drug effects ; Bone Marrow Cells/immunology ; Bone Marrow Cells/pathology ; Flow Cytometry/standards ; Gene Expression ; Hematologic Neoplasms/diagnosis ; Hematologic Neoplasms/drug therapy ; Hematologic Neoplasms/immunology ; Hematologic Neoplasms/mortality ; Humans ; Immunophenotyping/standards ; Lymphocytes/drug effects ; Lymphocytes/immunology ; Lymphocytes/pathology ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/drug therapy ; Neoplasm, Residual/immunology ; Neoplasm, Residual/mortality ; Prognosis ; Remission Induction ; Reproducibility of Results ; Sensitivity and Specificity ; Survival Analysis
    Chemical Substances Antibodies ; Antigens, CD ; Antineoplastic Agents
    Language English
    Publishing date 2016-01
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2099657-3
    ISSN 1552-4957 ; 1552-4949 ; 0196-4763
    ISSN (online) 1552-4957
    ISSN 1552-4949 ; 0196-4763
    DOI 10.1002/cyto.b.21239
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    Zs.A 1688: Show issues Location:
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  4. Article ; Online: Measurable Residual Disease Detection in B-Acute Lymphoblastic Leukemia: The Children's Oncology Group (COG) Method.

    Borowitz, Michael J / Wood, Brent L / Keeney, Michael / Hedley, Benjamin D

    Current protocols

    2022  Volume 2, Issue 3, Page(s) e383

    Abstract: Measurable (minimal) residual disease (MRD) in B-acute lymphoblastic leukemia (B-ALL), as assessed by flow cytometry, is an established prognostic factor used to adjust treatment in most pediatric therapeutic protocols. MRD in B-ALL has been standardized ...

    Abstract Measurable (minimal) residual disease (MRD) in B-acute lymphoblastic leukemia (B-ALL), as assessed by flow cytometry, is an established prognostic factor used to adjust treatment in most pediatric therapeutic protocols. MRD in B-ALL has been standardized by the Children's Oncology Group in North America and more recently in a multicenter Foundation for the National Institutes of Health-funded study. This article outlines the reagents, instrument setup, and analysis protocols required for the reproducible detection of residual leukemic cells in patients following induction therapy for B-ALL. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Staining and flow cytometry for B-acute lymphoblastic leukemia (B-ALL) measurable residual disease detection Support Protocol: Specimen collection, handling, storage, and shipping Basic Protocol 2: Analysis and interpretation of data for B-ALL measurable residual disease detection Basic Protocol 3: Analysis of samples lacking sufficient CD19+ events.
    MeSH term(s) Acute Disease ; Antigens, CD19 ; Child ; Flow Cytometry/methods ; Humans ; Neoplasm, Residual/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; United States
    Chemical Substances Antigens, CD19
    Language English
    Publishing date 2022-03-08
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ISSN 2691-1299
    ISSN (online) 2691-1299
    DOI 10.1002/cpz1.383
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  5. Article ; Online: Maturational dyssynchrony in benign B-cell precursors following lymphocyte depleting chemotherapy: A potential pitfall for B-lymphoblastic leukemia minimal/measurable residual disease (MRD) flow cytometry analysis.

    Placek, Alexander / Lockhart, Brian / Miller, Karin P / Wertheim, Gerald B / Maude, Shannon L / Wood, Brent L / Kovach, Alexandra E

    Cytometry. Part B, Clinical cytometry

    2024  Volume 106, Issue 2, Page(s) 138–141

    MeSH term(s) Humans ; Flow Cytometry ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Precursor Cells, B-Lymphoid ; Neoplasm, Residual
    Language English
    Publishing date 2024-01-21
    Publishing country United States
    Document type Letter
    ZDB-ID 2099657-3
    ISSN 1552-4957 ; 1552-4949 ; 0196-4763
    ISSN (online) 1552-4957
    ISSN 1552-4949 ; 0196-4763
    DOI 10.1002/cyto.b.22161
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  6. Article ; Online: Flow cytometric monitoring of residual disease in acute leukemia.

    Wood, Brent L

    Methods in molecular biology (Clifton, N.J.)

    2013  Volume 999, Page(s) 123–136

    Abstract: Multiparameter flow cytometry offers the unique ability to simultaneously assess and correlate multiple cellular properties at the single cell level in a timely and efficient manner. Application of this technique to the detection of residual acute ... ...

    Abstract Multiparameter flow cytometry offers the unique ability to simultaneously assess and correlate multiple cellular properties at the single cell level in a timely and efficient manner. Application of this technique to the detection of residual acute leukemia after therapy has been shown to be of singular importance to monitor response to therapy and provide prognostic information. Principles and methods that allow for the sensitive detection of acute leukemia following therapy are presented. The basic protocol outlines a simple and efficient method for the labeling of white cells with monoclonal antibodies directed against cell surface antigens. A second method describes a general method for the simultaneous assessment of surface and cytoplasmic antigens using a combination of fixation followed by membrane permeabilization. An illustrative panel of validated reagents currently in use for residual disease detection for acute lymphoblastic leukemia of B or T cell lineage as well as acute myeloid leukemia is provided. Principles of data analysis that allow for the reproducible detection of small populations of abnormal hematopoietic cells in peripheral blood and bone marrow are presented.
    MeSH term(s) Antibodies, Monoclonal ; Antigens, Neoplasm/immunology ; Antigens, Neoplasm/isolation & purification ; Antigens, Surface/isolation & purification ; Bone Marrow/pathology ; Flow Cytometry/methods ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/immunology ; Leukemia, Myeloid, Acute/pathology ; Neoplasm, Residual/diagnosis ; Neoplasm, Residual/genetics ; Neoplasm, Residual/pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology
    Chemical Substances Antibodies, Monoclonal ; Antigens, Neoplasm ; Antigens, Surface
    Language English
    Publishing date 2013
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-62703-357-2_8
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  7. Article ; Online: Methods of Detection of Measurable Residual Disease in AML.

    Zhou, Yi / Wood, Brent L

    Current hematologic malignancy reports

    2017  Volume 12, Issue 6, Page(s) 557–567

    Abstract: The presence of measurable ("minimal") residual disease (MRD) after induction and/or consolidation chemotherapy is a significant risk factor for relapse in patients with acute myeloid leukemia (AML). In recognition of the clinical significance of AML MRD, ...

    Abstract The presence of measurable ("minimal") residual disease (MRD) after induction and/or consolidation chemotherapy is a significant risk factor for relapse in patients with acute myeloid leukemia (AML). In recognition of the clinical significance of AML MRD, the European LeukemiaNet (ELN) recently recommended the establishment of CR-MRD
    MeSH term(s) Humans ; Leukemia, Myeloid, Acute/complications ; Neoplasm, Residual/diagnosis
    Language English
    Publishing date 2017-11-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2229765-0
    ISSN 1558-822X ; 1558-8211
    ISSN (online) 1558-822X
    ISSN 1558-8211
    DOI 10.1007/s11899-017-0419-5
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  8. Article ; Online: How do we measure MRD in ALL and how should measurements affect decisions. Re: Treatment and prognosis?

    Chen, Xueyan / Wood, Brent L

    Best practice & research. Clinical haematology

    2017  Volume 30, Issue 3, Page(s) 237–248

    Abstract: Minimal residual disease (MRD) is the most significant independent prognostic factor in acute lymphocytic leukemia (ALL). Monitoring MRD using sensitive techniques, including multiparametric flow cytometry (MFC) and quantitative polymerase chain reaction ...

    Abstract Minimal residual disease (MRD) is the most significant independent prognostic factor in acute lymphocytic leukemia (ALL). Monitoring MRD using sensitive techniques, including multiparametric flow cytometry (MFC) and quantitative polymerase chain reaction (qPCR)-based methods, has improved the assessment of treatment response and risk stratification for clinical management. New molecular methods, such as high-throughput next-generation sequencing (NGS), have evolved into routine laboratory tools to improve the sensitivity and specificity of MRD detection. It is essential to establish standardized protocols as to the timing of assessment and methodology used, to limit inter-laboratory variability. MRD has demonstrated utility for the identification of patients with suboptimal initial response to therapy who may benefit from more intensive or novel therapies, in addition to identifying patients with an excellent response to initial therapy who may be candidates for therapeutic reduction to limit toxicity. Herein, we review the methodological approaches to MRD detection in ALL and discuss the clinical implication of MRD in risk-directed therapy and practical issues.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; Clinical Decision-Making ; Disease Management ; Flow Cytometry ; Gene Expression Regulation, Leukemic ; High-Throughput Nucleotide Sequencing ; Humans ; Molecular Targeted Therapy ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Prognosis ; Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Signal Transduction
    Chemical Substances Antineoplastic Agents ; Neoplasm Proteins
    Language English
    Publishing date 2017-07-06
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2048027-1
    ISSN 1532-1924 ; 1521-6926
    ISSN (online) 1532-1924
    ISSN 1521-6926
    DOI 10.1016/j.beha.2017.07.002
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  9. Article ; Online: Applications of Flow Cytometric Immunophenotyping in the Diagnosis and Posttreatment Monitoring of B and T Lymphoblastic Leukemia/Lymphoma.

    DiGiuseppe, Joseph A / Wood, Brent L

    Cytometry. Part B, Clinical cytometry

    2019  Volume 96, Issue 4, Page(s) 256–265

    Abstract: In this review, we discuss applications of flow cytometric immunophenotyping (FCI) in the diagnostic evaluation and posttreatment monitoring of B and T lymphoblastic leukemia/lymphoma. We describe practical approaches to FCI at the time of diagnosis, ... ...

    Abstract In this review, we discuss applications of flow cytometric immunophenotyping (FCI) in the diagnostic evaluation and posttreatment monitoring of B and T lymphoblastic leukemia/lymphoma. We describe practical approaches to FCI at the time of diagnosis, with an emphasis on blast identification, lineage assignment, and distinction of B and T lymphoblastic leukemia/lymphoma from their morphologic and immunophenotypic mimics. We further review flow cytometric assays for the detection of minimal or measurable residual disease (MRD) after treatment, and illustrate both standard approaches, and newer strategies for improving sensitivity and circumventing the loss of immunophenotypic targets after immunotherapy. © 2019 International Clinical Cytometry Society.
    MeSH term(s) Flow Cytometry ; Humans ; Immunophenotyping ; Lymphoma/diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis
    Language English
    Publishing date 2019-06-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2099657-3
    ISSN 1552-4957 ; 1552-4949 ; 0196-4763
    ISSN (online) 1552-4957
    ISSN 1552-4949 ; 0196-4763
    DOI 10.1002/cyto.b.21833
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  10. Article ; Online: Immunophenotypic Features of Myeloid Neoplasms Associated with Chromosome 7 Abnormalities.

    Chen, Xueyan / Wood, Brent L / Cherian, Sindhu

    Cytometry. Part B, Clinical cytometry

    2019  Volume 96, Issue 4, Page(s) 300–309

    Abstract: Background: Abnormalities involving chromosome 7 are one of the most frequent chromosomal aberrations in myeloid neoplasms including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) and are associated with an adverse prognosis. ... ...

    Abstract Background: Abnormalities involving chromosome 7 are one of the most frequent chromosomal aberrations in myeloid neoplasms including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) and are associated with an adverse prognosis. Immunophenotyping by flow cytometry provides data that can assist in the diagnosis and classification of myeloid neoplasms. The immunophenotypic features of myeloid neoplasms with monosomy 7 or del(7q) have not been previously described in a comprehensive fashion.
    Methods: We retrospectively analyzed flow cytometric data of myeloid neoplasms with monosomy 7 or del(7q) and summarized associated immunophenotypic features.
    Results: Myeloid neoplasms with monosomy 7 typically demonstrate multiple immunophenotypic abnormalities on myeloid blasts and maturing myelomonocytic cells. Increased CD14 expression on maturing granulocytic cells was characteristically seen in myeloid neoplasms with monosomy 7. This abnormality was significantly more frequent in myeloid neoplasms with monosomy 7 than in those with del(7q) (92.9% vs. 8.2%, P < 0.0001). The presence of increased CD14 expression on maturing granulocytic cells could be seen in cases with monosomy 7 in the setting of a normal blast percentage and when minimal (<3) other immunophenotypic abnormalities were seen on myeloid populations.
    Conclusions: Increased CD14 expression on maturing granulocytic cells can be helpful in identifying patients with myeloid neoplasms who have monosomy 7. © 2019 International Clinical Cytometry Society.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Chromosome Aberrations ; Chromosomes, Human, Pair 7/genetics ; Female ; Flow Cytometry ; Humans ; Immunophenotyping ; Leukemia, Myeloid/diagnosis ; Leukemia, Myeloid/genetics ; Male ; Middle Aged ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/genetics ; Retrospective Studies ; Young Adult
    Language English
    Publishing date 2019-02-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2099657-3
    ISSN 1552-4957 ; 1552-4949 ; 0196-4763
    ISSN (online) 1552-4957
    ISSN 1552-4949 ; 0196-4763
    DOI 10.1002/cyto.b.21775
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