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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
Author(s) -
Xiao Wenbin,
Salem Dalia,
McCoy Catharine S.,
Lee Daniel,
Shah Nirali N.,
StetlerStevenson Maryalice,
Yuan Constance M.
Publication year - 2018
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.21591
Subject(s) - minimal residual disease , b cell , cd38 , cd19 , cd20 , immunophenotyping , cd34 , flow cytometry , antigen , microbiology and biotechnology , bone marrow , immunology , cancer research , antibody , biology , medicine , stem cell
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