Early recovery of circulating immature B cells in B-lymphoblastic leukemia patients after CD19 targeted CAR T cell therapy: A pitfall for minimal residual disease detection.

Autor: Xiao W; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.; Present address: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York., Salem D; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.; Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt., McCoy CS; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Lee D; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, Virginia., Shah NN; Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Stetler-Stevenson M; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Yuan CM; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Jazyk: angličtina
Zdroj: Cytometry. Part B, Clinical cytometry [Cytometry B Clin Cytom] 2018 May; Vol. 94 (3), pp. 434-443. Date of Electronic Publication: 2017 Oct 31.
DOI: 10.1002/cyto.b.21591
Abstrakt: Background: CD19-targeted chimeric-antigen receptor-modified T-cells (CAR-T) are promising in the treatment of refractory B-lymphoblastic leukemia (B-ALL). Minimal residual disease (MRD) detection by multicolor flow cytometry (FCM) is critical to distinguish B-ALL MRD from regenerating, non-neoplastic B-cell populations.
Methods: FCM was performed on samples from 9 patients with B-ALL treated with CAR-T.
Results: All 9 patients showed response to CAR-T. Additionally, FCM revealed circulating CD10 + B cells, potentially mimicking MRD. Circulating CD10+ B-cells were detected in blood from 3 days to 3 months after CAR-T, comprising 73% (median) of B-cells (52-83%, 95%CI). They expressed CD19, CD10, CD20, bright CD9, CD22, CD24, moderate CD38 and dim CD58, but were CD34 (-), with bright CD45 and polyclonal surface light chain immunoglobulin (sIg) expression. A similar CD10 + B-cell subpopulation was detected by marrow FCM, amidst abundant B-cell precursors.
Conclusions: These circulating CD10 + B-cells are compatible with immature B-cells, and are a reflection of B-cell recovery within the marrow. They are immunophenotypically distinguishable from residual B-ALL. Expression of light chain sIg and key surface antigens characterizing regenerating B-cell precursors can distinguish immature B-cells from B-ALL MRD and prevent misdiagnosis. © 2017 International Clinical Cytometry Society.
(© 2017 International Clinical Cytometry Society.)
Databáze: MEDLINE
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