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. Issue 3 (31st October 2017)

• Record Type: Journal Article
• Authors: Xiao, Wenbin; Salem, Dalia; McCoy, Catharine S.; Lee, Daniel; Shah, Nirali N.; Stetler‐Stevenson, Maryalice; Yuan, Constance M.
• Is Part Of: Cytometry. Volume 94:Issue 3(2018)
• Page Start: 434
• Page End: 443
• Publication Date: 2017-10-31
• Subjects: B‐lymphoblastic leukemia -- ALL -- CD19 -- CAR T cells -- chimeric antigen receptor -- flow cytometry -- minimal residual disease -- circulating CD10+ B cells -- transitional B cells -- immature B cells; Flow cytometry -- Diagnostic use -- Periodicals; Cytodiagnosis -- Periodicals; 616.07582
• DOI: 10.1002/cyto.b.21591
• Languages: English
• ISSNs: 1552-4949

Abstract

Abstract : 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