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.

Autor: Mikhailova E; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Semchenkova A; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Illarionova O; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Kashpor S; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Brilliantova V; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Zakharova E; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Zerkalenkova E; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Zangrando A; Maternal and Child Health Department, University of Padua, Padua, Italy.; Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy., Bocharova N; BD Biosciences, Moscow, Russian Federation., Shelikhova L; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Diakonova Y; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Zhogov V; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Khismatullina R; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Molostova O; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Buldini B; Maternal and Child Health Department, University of Padua, Padua, Italy., Raykina E; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Larin S; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Olshanskaya Y; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Miakova N; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Novichkova G; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Maschan M; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation., Popov AM; National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2021 May; Vol. 193 (3), pp. 602-612. Date of Electronic Publication: 2021 Mar 14.
DOI: 10.1111/bjh.17382
Abstrakt: 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.
(© 2021 British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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