Kinetics of hematogones in bone marrow samples from patients with non-Hodgkin lymphomas treated with rituximab-containing regimens: a flow cytometric study

Abstract

Treatment with rituximab, either alone or in combination with antiblastic drugs, causes significant depletion of circulating B-lymphocytes and modifications of B cell maturation in the bone marrow. In the present study, we analyzed the kinetics of hematogones in bone marrow samples from 55 patients suffering from non-Hodgkin lymphomas and treated with rituximab-containing regimens. Maturation arrest at the level of stage 2 hematogones, along with complete depletion of naïve, mature B-lymphocytes, was observed as short-term effects (2 months after completion of chemo-immunotherapy). Further bone marrow samples, obtained 12 months after the last rituximab infusion in 21 patients undergoing long-term follow-up and treated with rituximab maintenance therapy, showed complete normalization of B-lymphocyte ontogeny. Hypogammaglobulinemia developed in 26 patients, and was still observed in nine of the 21 patients undergoing long-term follow-up. Our study provides novel data on hematogone kinetics in the setting of patients with non-Hodgkin lymphomas treated with chemo-immunotherapy containing rituximab and with rituximab maintenance. Our observations show that hypogammaglobulinemia can persist in a significant percentage of patients, despite complete recovery of B-lymphocyte ontogeny.

Abnormal B-cell maturation in the bone marrow of patients with germline mutations in PIK3CD

“…Flow cytometric immunophenotyping of BM was performed in 7 patients, and the results were compared to 6 age-matched BM controls (see Methods in Online Repository and Table E1) using the Mann-Whitney test. B-cell maturation was assessed using immunophenotypic criteria for B-cell developmental stages previously described 7, 8 . A p value of <0.05 was considered significant.…”

“…However, in addition to the maturation block, B-ALL commonly shows expression of aberrant markers or phenotypic asynchrony 7 which was not seen in PIK3CD GOF marrows. Other benign conditions, which can demonstrate transient overlapping features include immune reconstitution following BM transplantation, chemotherapy, or treatment with rituximab 7, 8 .…”

Baseline immunoglobulin G and immune function in non-Hodgkin lymphoma: a retrospective analysis

“…Of patients who received anti-CD20 antibody, 45.2% developed low IgG. Hypogammaglobulinema has been associated with cumulative dose of anti-CD20 antibodies ( 17 , 23 ); the proposed mechanism through permanent damage of B-cell maturation and blocking of plasma cell differentiation ( 18 ). Previous studies have linked prolonged antibody-induced hypogammaglobulinemia with low baseline serum immunoglobulin level with OR 4.2 (95% CI 1.26-14.1) ( 24 , 25 ).…”

Flow cytometric assessment for minimal/measurable residual disease in B lymphoblastic leukemia/lymphoma in the era of immunotherapy

“…As CD20 targeting monoclonal antibodies have been in clinical use for over 30 years, there is significant data regarding the impact of anti‐CD20 mAbs on antigen expression. In patients with non‐Hodgkin lymphomas treated with anti‐CD20 mAb rituximab, B cell maturation arrest occurs at the early stage 2 hematogone and is accompanied by complete depletion of naïve, mature B cells (Carulli et al, 2015) (Figure 2). These changes were reported as short‐term effects, with complete normalization of B cell ontogeny 12 months after the last rituximab infusion (Carulli et al, 2015).…”

“…In patients with non‐Hodgkin lymphomas treated with anti‐CD20 mAb rituximab, B cell maturation arrest occurs at the early stage 2 hematogone and is accompanied by complete depletion of naïve, mature B cells (Carulli et al, 2015) (Figure 2). These changes were reported as short‐term effects, with complete normalization of B cell ontogeny 12 months after the last rituximab infusion (Carulli et al, 2015). Anti‐CD20 therapy may also lead to reduction of CD19 expression (Jones et al, 2012), and in practice, reduced intensity of CD19 may be seen on B cells persisting post anti‐CD20 therapy, a variable which can complicate use of CD19 as a B cell gating reagent.…”