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      Minimal residual disease assessment in acute lymphoblastic leukemia by 4-color flow cytometry: Recommendations from the MRD Working Group of the Brazilian Society of Bone Marrow Transplantation

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          Abstract

          Introduction

          The minimal residual disease (MRD) status plays a crucial role in the treatment of acute lymphoblastic leukemia (ALL) and is currently used in most therapeutic protocols to guide the appropriate therapeutic decision. Therefore, it is imperative that laboratories offer accurate and reliable results through well standardized technical processes by establishing rigorous operating procedures.

          Method

          Our goal is to propose a monoclonal antibody (MoAb) panel for MRD detection in ALL and provide recommendations intended for flow cytometry laboratories that work on 4-color flow cytometry platforms.

          Results and conclusion

          The document includes pre-analytical and analytical procedures, quality control assurance, technical procedures, as well as the information that needs to be included in the reports for clinicians.

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          Most cited references62

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          EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes

          J van Dongen, L Lhermitte, S Böttcher … (2012)
          Most consensus leukemia & lymphoma antibody panels consist of lists of markers based on expert opinions, but they have not been validated. Here we present the validated EuroFlow 8-color antibody panels for immunophenotyping of hematological malignancies. The single-tube screening panels and multi-tube classification panels fit into the EuroFlow diagnostic algorithm with entries defined by clinical and laboratory parameters. The panels were constructed in 2–7 sequential design–evaluation–redesign rounds, using novel Infinicyt software tools for multivariate data analysis. Two groups of markers are combined in each 8-color tube: (i) backbone markers to identify distinct cell populations in a sample, and (ii) markers for characterization of specific cell populations. In multi-tube panels, the backbone markers were optimally placed at the same fluorochrome position in every tube, to provide identical multidimensional localization of the target cell population(s). The characterization markers were positioned according to the diagnostic utility of the combined markers. Each proposed antibody combination was tested against reference databases of normal and malignant cells from healthy subjects and WHO-based disease entities, respectively. The EuroFlow studies resulted in validated and flexible 8-color antibody panels for multidimensional identification and characterization of normal and aberrant cells, optimally suited for immunophenotypic screening and classification of hematological malignancies.
          Article 0 comments Cited 272 times – based on 0 reviews     Review now
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            Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy.

            Rebecca Gardner, David Wu, Sindhu Cherian … (2016)
            Administration of lymphodepletion chemotherapy followed by CD19-specific chimeric antigen receptor (CAR)-modified T cells is a remarkably effective approach to treating patients with relapsed and refractory CD19(+) B-cell malignancies. We treated 7 patients with B-cell acute lymphoblastic leukemia (B-ALL) harboring rearrangement of the mixed lineage leukemia (MLL) gene with CD19 CAR-T cells. All patients achieved complete remission (CR) in the bone marrow by flow cytometry after CD19 CAR-T-cell therapy; however, within 1 month of CAR-T-cell infusion, 2 of the patients developed acute myeloid leukemia (AML) that was clonally related to their B-ALL, a novel mechanism of CD19-negative immune escape. These reports have implications for the management of patients with relapsed and refractory MLL-B-ALL who receive CD19 CAR-T-cell therapy.
            Article 0 comments Cited 201 times – based on 0 reviews     Review now
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              Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study.

              Michael J. Borowitz, Meenakshi Devidas, Stephen P. Hunger … (2008)
              Minimal residual disease (MRD) is an important predictor of relapse in acute lymphoblastic leukemia (ALL), but its relationship to other prognostic variables has not been fully assessed. The Children's Oncology Group studied the prognostic impact of MRD measured by flow cytometry in the peripheral blood at day 8, and in end-induction (day 29) and end-consolidation marrows in 2143 children with precursor B-cell ALL (B-ALL). The presence of MRD in day-8 blood and day-29 marrow MRD was associated with shorter event-free survival (EFS) in all risk groups; even patients with 0.01% to 0.1% day-29 MRD had poor outcome compared with patients negative for MRD patients (59% +/- 5% vs 88% +/- 1% 5-year EFS). Presence of good prognostic markers TEL-AML1 or trisomies of chromosomes 4 and 10 still provided additional prognostic information, but not in National Cancer Institute high-risk (NCI HR) patients who were MRD(+). The few patients with detectable MRD at end of consolidation fared especially poorly, with only a 43% plus or minus 7% 5-year EFS. Day-29 marrow MRD was the most important prognostic variable in multi-variate analysis. The 12% of patients with all favorable risk factors, including NCI risk group, genetics, and absence of days 8 and 29 MRD, had a 97% plus or minus 1% 5-year EFS with nonintensive therapy. These studies are registered at www.clinicaltrials.gov as NCT00005585, NCT00005596, and NCT00005603.
              Article 0 comments Cited 181 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Maura R.V. Ikoma-Colturato
                Journal
                Journal ID (nlm-ta): Hematol Transfus Cell Ther
                Journal ID (iso-abbrev): Hematol Transfus Cell Ther
                Title: Hematology, Transfusion and Cell Therapy
                Publisher: Sociedade Brasileira de Hematologia e Hemoterapia
                ISSN (Print): 2531-1379
                ISSN (Electronic): 2531-1387
                Publication date PMC-release: 21 November 2020
                Publication date (Print): Jul-Sep 2021
                Publication date (Electronic): 21 November 2020
                Volume: 43
                Issue: 3
                Pages: 332-340
                Affiliations
                [a ]Hospital Amaral Carvalho, Jaú, SP, Brazil
                [b ]Sabin Medicina Diagnóstica, Brasília, DF, Brazil
                [c ]Hospital Erasto Gaertner, Curitiba, PR, Brazil
                [d ]Hospital da Criança de Brasília José de Alencar, Brasilia, DF, Brazil, Brazil
                [e ]Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
                [f ]Hospital de Clínicas Universidade Federal do Paraná (UFPR), Curitiba, PR, Brazil
                [g ]Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
                Author notes
                [* ] Corresponding author at: Rua das Palmeiras, 150, Jau, SP, CEP: 17210-120, Brazil. maura.ikoma@ 123456amaralcarvalho.org.br
                Article
                Publisher Item ID: S2531-1379(20)31289-X
                DOI: 10.1016/j.htct.2020.09.148
                PMC ID: 8446261
                PubMed ID: 33281111
                SO-VID: 675b2f8c-3fc3-4f14-a97c-abd3cab2a2db
                Copyright © © 2020 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 28 June 2020
                Date accepted : 1 September 2020
                Categories
                Subject: Special Article

                Keywords: minimal residual disease,acute lymphoblastic leukemia,flow cytometry
                Data availability:
                Keywords: minimal residual disease, acute lymphoblastic leukemia, flow cytometry

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