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Chapter 6 - Acute Lymphoid Leukaemia and Minimal/Measurable Residual Disease

Published online by Cambridge University Press:  30 January 2025

By
Barbara Buldini ,
Elena Varotto  and
Andrea Zangrando
Edited by
Anna Porwit  and
Marie Christine Béné
Anna Porwit
Affiliation:
Lunds Universitet, Sweden
Marie Christine Béné
Affiliation:
Université de Nantes, France
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Summary

Acute lymphoblastic leukaemia (ALL) is the most common cancer in childhood but shows a very low frequency in adults. Even in the genomics era, multiparametric flow cytometry is still critical for ALL diagnosis and management. At diagnosis, it determines the proper therapeutic approach through blast characterization and lineage assignment. During treatment, it is an essential tool for response to therapy monitoring through minimal/measurable residual disease detection. Additionally, multiparametric flow cytometry is fundamental in the even more applied immunotherapy setting, recognizing any potential switch of blast immunophenotype.

Keywords

flow cytometryacute lymphoblastic leukemiaB-lineageT-lineageclassificationpanelsimmunophenotypingmeasurable/minimal residual diseaseimmunotherapieslineage switch
Type
Chapter
Information
Multiparameter Flow Cytometry in the Diagnosis of Hematologic Malignancies , pp. 93 - 107
Publisher: Cambridge University Press
Print publication year: 2025

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References

Temple, WC, Mueller, S, Hermiston, ML, Burkhardt, B. Diagnosis and management of lymphoblastic lymphoma in children, adolescents and young adults. Best Pract Res Clin Haematol 2023; 36: 101449.CrossRefGoogle ScholarPubMed
Ivanov, AV, Alecsa, MS, Popescu, R, et al. Pediatric acute lymphoblastic leukemia emerging therapies-from pathway to target. Int J Mol Sci 2023; 24: 4661.CrossRefGoogle ScholarPubMed
Jabbour, E, Short, NJ, Jain, N, et al. The evolution of acute lymphoblastic leukemia research and therapy at MD Anderson over four decades. J Hematol Oncol 2023; 16: 22.CrossRefGoogle Scholar
Alaggio, R, Amador, C, Anagnostopoulos, I, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia 2022; 36: 1720–1748.CrossRefGoogle ScholarPubMed
Arber, DA, Orazi, A, Hasserjian, RP, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood 2022; 140: 1200–1228.CrossRefGoogle ScholarPubMed
Panuciak, K, Nowicka, E, Mastalerczyk, A, Zawitkowska, J, Niedźwiecki, M, Lejman, M. Overview on aneuploidy in childhood B-cell acute lymphoblastic leukemia. Int J Mol Sci 2023; 24: 8764.CrossRefGoogle ScholarPubMed
Hrusák, O, Porwit-MacDonald, A. Antigen expression patterns reflecting genotype of acute leukemias. Leukemia 2002; 16: 1233–1258.CrossRefGoogle ScholarPubMed
DiGiuseppe, JA, Wood, BL. Applications of flow cytometric immunophenotyping in the diagnosis and posttreatment monitoring of B and T lymphoblastic leukemia/lymphoma. Cytometry B Clin Cytom 2019; 96: 256–265.CrossRefGoogle ScholarPubMed
Kovach, AE, Wood, BL. Updates on lymphoblastic leukemia/lymphoma classification and minimal/measurable residual disease analysis. Semin Diagn Pathol 2023; 40: 457–471.CrossRefGoogle ScholarPubMed
Choi, JK, Mead, PE. Laboratory aspects of minimal/measurable residual disease testing in B-lymphoblastic leukemia. Clin Lab Med 2023; 43: 115–125.CrossRefGoogle ScholarPubMed
Chen, X, Gao, Q, Roshal, M, Cherian, S. Flow cytometric assessment for minimal/measurable residual disease in B lymphoblastic leukemia/lymphoma in the era of immunotherapy. Cytometry B Clin Cytom 2023; 104: 205–223.CrossRefGoogle Scholar
Dworzak, MN, Buldini, B, Gaipa, G, et al. AIEOP-BFM consensus guidelines 2016 for flow cytometric immunophenotyping of pediatric acute lymphoblastic leukemia. Cytometry B Clin Cytom 2018; 94: 82–93.CrossRefGoogle ScholarPubMed
Béné, MC, Castoldi, G, Knapp, W, et al. Proposals for the immunological classification of acute leukemias: European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995; 9: 1783–1786.Google Scholar
Cherian, S, Soma, LA. How I diagnose minimal/measurable residual disease in B lymphoblastic leukemia/lymphoma by flow cytometry. Am J Clin Pathol 2021; 155: 38–54.CrossRefGoogle Scholar
Coustan-Smith, E, Mullighan, CG, Onciu, M, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 2009; 10: 147–156.CrossRefGoogle ScholarPubMed
Conter, V, Valsecchi, MG, Buldini, B, et al. Early T-cell precursor acute lymphoblastic leukaemia in children treated in AIEOP centres with AIEOP-BFM protocols: a retrospective analysis. Lancet Haematol 2016; 3: e80–e86.CrossRefGoogle ScholarPubMed
Pieters, R, Mullighan, CG, Hunger, SP. Advancing diagnostics and therapy to reach universal cure in childhood ALL. J Clin Oncol 2023; 41: 5579–5591.CrossRefGoogle ScholarPubMed
Gaipa, G, Basso, G, Biondi, A, Campana, D. Detection of minimal residual disease in pediatric acute lymphoblastic leukemia. Cytometry B Clin Cytom 2013; 84: 359–369.CrossRefGoogle ScholarPubMed
Paganin, M, Fabbri, G, Conter, V, et al. Postinduction minimal residual disease monitoring by polymerase chain reaction in children with acute lymphoblastic leukemia. J Clin Oncol 2014; 32: 3553–3558.CrossRefGoogle ScholarPubMed
Zhang, J, Oak, J. Challenges of detecting measurable/minimal disease in acute leukemia. Semin Diagn Pathol 2023; 40: 216–220.CrossRefGoogle ScholarPubMed
Basso, G, Veltroni, M, Valsecchi, MG, et al. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol 2009; 27: 5168–5174.CrossRefGoogle ScholarPubMed
Loosveld, M, Nivaggioni, V, Arnoux, I, et al. Early (day 15 post diagnosis) peripheral blood assessment of measurable residual disease in flow cytometry is a strong predictor of outcome in childhood B-lineage lymphoblastic leukemia. Cytometry B Clin Cytom 2019; 96: 128–133.CrossRefGoogle Scholar
Eveillard, M, Robillard, N, Arnoux, I, et al. Major impact of an early bone marrow checkpoint (day 21) for minimal residual disease in flow cytometry in childhood acute lymphoblastic leukemia. Hematol Oncol 2017; 35: 237–243.CrossRefGoogle Scholar
Campbell, M, Kiss, C, Zimmermann, M, et al. Childhood acute lymphoblastic leukemia: results of the randomized acute lymphoblastic leukemia intercontinental-Berlin-Frankfurt-Münster 2009 trial. J Clin Oncol 2023; 41: 3499–3511.CrossRefGoogle ScholarPubMed
Maurer-Granofszky, M, Schumich, A, Buldini, B, et al. An extensive quality control and quality assurance (QC/QA) program significantly improves inter-laboratory concordance rates of flow-cytometric minimal residual disease assessment in acute lymphoblastic leukemia: an I-BFM-FLOW-Network report. Cancers 2021; 13: 6148.CrossRefGoogle ScholarPubMed
Theunissen, P, Mejstrikova, E, Sedek, L, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood 2017; 129: 347–357.CrossRefGoogle ScholarPubMed
Kowarsch, F, Maurer-Granofszky, M, Weijler, L, et al. FCM marker importance for MRD assessment in T-cell acute lymphoblastic leukemia: an AIEOP-BFM-ALL-FLOW study group report. Cytometry A 2023 Epub ahead of print.CrossRefGoogle Scholar
Tsitsikov, E, Harris, MH, Silverman, LB, Sallan, SE, Weinberg, OK. Role of CD81 and CD58 in minimal residual disease detection in pediatric B lymphoblastic leukemia. Int J Lab Hematol 2018; 40: 343–351.CrossRefGoogle ScholarPubMed
Buldini, B, Faggin, G, Porcù, E, et al. CD72 is a pan-tumor antigen associated to pediatric acute leukemia. Cytometry A. 2023; 103: 1004–1009.CrossRefGoogle ScholarPubMed
Buchmann, S, Schrappe, M, Baruchel, A, et al. Remission, treatment failure, and relapse in pediatric ALL: an international consensus of the Ponte-di-Legno Consortium. Blood 2022; 139: 1785–1793.CrossRefGoogle ScholarPubMed
Davis, KL, Mackall, CL. Immunotherapy for acute lymphoblastic leukemia: from famine to feast. Blood Adv 2016; 1: 265–269.CrossRefGoogle ScholarPubMed
Myers, RM, Dolan, J, Teachey, DT. Chimeric antigen receptor T cell therapy for pediatric and young adult B cell acute lymphoblastic leukemia. Expert Rev Clin Immunol 2020; 16: 1029–1042.CrossRefGoogle Scholar
van der Sluis, IM, de Lorenzo, P, Kotecha, RS, et al. Blinatumomab added to chemotherapy in infant lymphoblastic leukemia. N Engl J Med 2023; 388: 1572–1578CrossRefGoogle ScholarPubMed
Stokke, JL, Bhojwani, D. Antibody-drug conjugates for the treatment of acute pediatric leukemia. J Clin Med 2021; 10: 3556.CrossRefGoogle ScholarPubMed
Vakrmanová, B, Nováková, M, Říha, P, et al. CD38: a target in relapsed/refractory acute lymphoblastic leukemia-limitations in treatment and diagnostics. Pediatr Blood Cancer. 2022; 69: e29779.CrossRefGoogle ScholarPubMed
Laetsch, TW, Maude, SL, Rives, S, et al. Three-year update of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia in the ELIANA Trial. J Clin Oncol. 2023; 41: 1664–1669.CrossRefGoogle Scholar
Pan, J, Niu, Q, Deng, B, et al. CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia. Leukemia 2019; 33: 2854–2866.CrossRefGoogle ScholarPubMed
Bhojwani, D, Sposto, R, Shah, NN, et al. Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Leukemia 2019; 33: 884–892.CrossRefGoogle ScholarPubMed
Brivio, E, Locatelli, F, Lopez-Yurda, M, et al. A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study). Blood 2021; 137: 1582–1590.CrossRefGoogle ScholarPubMed
Martino, M, Alati, C, Canale, FA, Musuraca, G, Martinelli, G, Cerchione, C. A review of clinical outcomes of CAR T-cell therapies for B-acute lymphoblastic leukemia. Int J Mol Sci 2021; 22: 2150.CrossRefGoogle ScholarPubMed
Brivio, E, Baruchel, A, Beishuizen, A, et al. Targeted inhibitors and antibody immunotherapies: novel therapies for paediatric leukaemia and lymphoma. Eur J Cancer 2022; 164: 1–17.CrossRefGoogle ScholarPubMed
Freiwan, A, Zoine, JT, Crawford, JC, et al. Engineering naturally occurring CD7- T cells for the immunotherapy of hematological malignancies. Blood 2022; 140: 2684–2696.CrossRefGoogle ScholarPubMed
Gupta, S, Kohorst, M, Alkhateeb, HB. Determinants of outcomes and advances in CD19-directed chimeric antigen receptor therapy for B-cell acute lymphoblastic leukemia. Eur J Haematol 2024; 112: 51–63.CrossRefGoogle ScholarPubMed
Fry, TJ, Shah, NN, Orentas, RJ, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med 2018; 24: 20–28.CrossRefGoogle ScholarPubMed
Mikhailova, E, Semchenkova, A, Illarionova, O, et al. 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. Br J Haematol 2021; 193: 602–612.CrossRefGoogle ScholarPubMed
Cherian, S, Miller, V, McCullouch, V, Dougherty, K, Fromm, JR, Wood, BL. A novel flow cytometric assay for detection of residual disease in patients with B-lymphoblastic leukemia/lymphoma post anti-CD19 therapy. Cytometry B Clin Cytom 2018; 94: 112–120.CrossRefGoogle ScholarPubMed
Sperlazza, J, Galeotti, J, Hucks, G, Alexander, TB. Multiple lineage switches in KMT2A rearranged infant leukemia, responsive to combination therapy with CPX-351 and inotuzumab. Pediatr Blood Cancer 2023; 70: e30645.CrossRefGoogle ScholarPubMed
Tirtakusuma, R, Szoltysek, K, Milne, P, et al. Epigenetic regulator genes direct lineage switching in MLL/AF4 leukemia. Blood 2022; 140: 1875–1890.CrossRefGoogle ScholarPubMed
Lamble, AJ, Myers, RM, Taraseviciute, A, et al. Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells. Blood Adv 2023; 7: 575–585.CrossRefGoogle ScholarPubMed
Coorens, THH, Collord, G, Treger, TD, et al. Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy. Nat Cancer 2023; 4: 1095–1101.CrossRefGoogle ScholarPubMed
Suematsu, M, Yagyu, S, Yoshida, H, et al. Targeting FLT3-specific chimeric antigen receptor T cells for acute lymphoblastic leukemia with KMT2A rearrangement. Cancer Immunol Immunother 2023; 72: 957–968.CrossRefGoogle ScholarPubMed
Slamova, L, Starkova, J, Fronkova, E, et al. CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage. Leukemia 2014; 28: 609–620.CrossRefGoogle Scholar
Buldini, B, Varotto, E, Maurer-Granofszky, M, et al. CD371+ pediatric B-cell acute lymphoblastic leukemia: propensity to lineage switch and slow early response to treatment. Blood 2024 Apr 25;143(17):1738-1751. blood.2023021952. PMID: 38215390.CrossRefGoogle Scholar
Shaffer, LG, McGowan-Jordan, J, Schmid, M (Eds). ISCN 2013 – An International System for Human Cytogenetic Nomenclature (Karger, Basel, 2013).Google Scholar

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