D2.489 - B-Cell Subset Reconstitution After Rituximab-Containing Chemotherapy in Children and Adolescents With Non-Hodgkin Lymphoma: A Single-Center Experience

B-cell aplasia, potentially followed by secondary hypogammaglobulinemia, represents a recognized on-target off-treatment effect of B-cell–targeted-immunotherapy in B-cell lymphoid malignancies. However, data on the incidence of hypogammaglobulinemia and the kinetics of B-cell subset reconstitution in children and adolescents with B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab (RTX) containing protocols remain limited.

A single-center retrospective study was performed to evaluate the impact of single versus multiple RTX-containing treatment  B-NHL protocols on immunoglobulin levels and B-cell subset reconstitution in pediatric and adolescent patients on the first 800 days of follow-up (FU) after the end-of-treatment(EoT).

B-cell subsets were defined according to surface marker expression as follows: transitional CD24++CD38++, naïve CD27-IgM+, marginal zone CD27+IgM+, isotype-switched memory CD27+IgM-, plasmablasts CD24+CD38++, CD21low- CD21lowCD38low B cells. Serum immunoglobulin concentrations (IgG, IgA, and IgM) were determined using a standardized nephelometric assay.

Twenty-four patients were included in the analysis. Nineteen patients (15 with Burkitt lymphoma BL-NHL, 3 with diffuse large B-cell lymphoma DLBCL, and 1 with marginal zone B-cell lymphoma) received a single-dose rituximab (RTX)–containing protocol. Two patients (1 DLBCL, 1 follicular B-NHL) were treated with multi-dose RTX protocols. Three patients with Nijmegen breakage syndrome (NBS)-2 DLBCL, 1 BL-NHL received either single- or multiple-dose RTX-containing protocols.

In the single-dose-RTX group, the median of B-cell reconstitution was the third month of FU. The reconstitution followed the pattern of early B-cell ontogeny. Initial predominance of transitional and naïve B cells was present. The proportion of patients with IgG, IgA, and IgM hypogammaglobulinemia declined over the FU period.

In the multiple-dose RTX group, median B-cell repopulation occurred at the fifth month of FU and demonstrated a similar reconstitution pattern to that of the single-RTX group. One patient experienced a transient decrease in IgG and IgM levels following B-cell recovery.

Patients with NBS exhibited prolonged B-cell repopulation, with persistent predominance of naïve and marginal zone B cells with markedly elevated CD21low B cells. IgG levels were not evaluated due to ongoing immunoglobulin replacement therapy (IgRT).

Neither single nor multiple-RTX-containing chemotherapeutic regimens resulted in clinically manifested antibody deficiency requiring IgRT.  

RTX-containing chemotherapy predominantly induces transitional CD20+ B-cell aplasia. Post-treatment monitoring of humoral and cellular immunity is essential. In cases of prolonged or atypical B-cell recovery with clinically significant profound hypogammaglobulinemia, genetic evaluation should be considered.