Persistent hypogammaglobulinemia after rituximab therapy in pediatric patients, prevalence and clinical outcomes

Abstract

Hypogammaglobulinemia is a known side effect of rituximab (RTX) in adults, but its prevalence and persistence in children remain underexplored. This retrospective cohort study at a tertiary care center examines the prevalence and clinical outcomes of hypogammaglobulinemia in pediatric patients after RTX therapy. Patients aged ≤ 18 years treated with RTX for various indications between 2000 and 2020 were included. Patients were classified as having hypogammaglobulinemia when (1) IgG levels were <-2SD below reference for age, or (2) when they received immunoglobulin replacement therapy (IGRT) for the indication hypogammaglobulinemia. Hypogammaglobulinemia after RTX treatment was observed in 74/134 patients (55.2 %). Persistent hypogammaglobulinemia (>6 months) was observed in 46/91 patients (50.5 %), of whom 9 patients remained hypogammaglobulinemic >5 years. Low baseline IgG and IgM levels were significantly associated with persistent hypogammaglobulinemia, while patients receiving RTX therapy for autoimmune diseases were less frequently affected. CD19⁺ B cells reconstituted in a median of 11 months (IQR=[7.3–18.0]), while CD19⁺CD27⁺IgG⁺ switched memory B cells took significantly longer, with a median of 1.8 years (IQR=[1.0–2.9]). Three patients developed class-switch recombination-deficiencies and never recovered. Recurrent infections, of which two fatal, were recorded in 18 patients and were significantly more prevalent in those with persistent hypogammaglobulinemia. In conclusion, over half of children had low IgG levels and/or required IGRT for hypogammaglobulinemia following RTX therapy. Persistent hypogammaglobulinemia was associated with low pre-RTX IgG and/or IgM levels. Children with hypogammaglobulinemia after RTX are often IGRT-dependent, experience recurrent (and sometimes fatal) infections, and may develop secondary immunoglobulin class-switch defects.