ALL-374 Mature B Cells, B-Cell Progenitors, and Plasma Cells in B-Cell Acute Lymphoblastic Leukemia Patients Enrolled in the RALL-2016 Study

Abstract

The numbers of normal, mature B cells (MBC), B-cell progenitors (BCP), and plasma cells (PC) in B-cell acute lymphoblastic leukemia (B-ALL) patients provide the possibility of an antigen-associated immune response. The aim of the study was to assess the amount of MBC, BCP, and PC in B-ALL patients enrolled in the RALL-2016 study at different stages of the protocol. This study included data from 2016 to 2020 from patients enrolled in the Russian multicenter study RALL-2016 (NCT03462095). The amounts of MBC, BCP, and PC and minimal residual disease (MRD) status were assessed in the bone marrow (BM) by flow cytometry. We assessed the MRD status and the numbers of MBC, BCP, and PC in 88 patients with B-ALL at all points of the protocol and maintenance therapy. Analysis of MRD status was performed by 6- or 10-color flow cytometry. To analyze the dynamics of changes in the number of B cells depending on the MRD status, on the 70th day of therapy, regression dependences were done. Differences between groups of patients and donors (n=5) were estimated with ANOVA. During therapy, the numbers of MBC (P<0.0001) and BCP (P<0.0001) significantly changed and did not depend on the MRD status (P>0.05) on the 70th day of therapy (P<0.0001). The counts of MBC and BCP were less in B-ALL patients than in donors at all stages of therapy. There was no change in the number of normal PC. The obtained results indicate that the cytostatic treatment used in the RALL-2016 protocol had a minimal effect on differentiated B cells. In this way, a stable number of the most differentiated B cells can contribute to the maintenance of humoral immunity. BCP were more sensitive to cytostatic effects and were not recovered for more than a year after the end of treatment. The absence of changes in PC count may indicate the resistance of this cell population to ongoing chemotherapy.