TY - JOUR
T1 - Persistent hypogammaglobulinemia after rituximab therapy in pediatric patients, prevalence and clinical outcomes
T2 - Hypogammaglobulinemia After Rituximab in Children
AU - Höppener, Susanna P.C.
AU - Veldkamp, Saskia R.
AU - de Groot, Mark C.H.
AU - Haitjema, Saskia
AU - Drylewicz, Julia
AU - Boelens, Jaap Jan
AU - Lindemans, Caroline A.
AU - van Montfrans, Joris
AU - van Royen-Kerkhof, Annet
AU - Jansen, Marc H.A.
N1 - Publisher Copyright:
© 2025
PY - 2025/6
Y1 - 2025/6
N2 - 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.
AB - 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.
KW - B cell reconstitution
KW - Hypogammaglobulinemia
KW - Pediatric
KW - Rituximab
UR - https://www.scopus.com/pages/publications/105004888015
U2 - 10.1016/j.clicom.2025.04.001
DO - 10.1016/j.clicom.2025.04.001
M3 - Article
AN - SCOPUS:105004888015
SN - 2772-6134
VL - 7
SP - 55
EP - 63
JO - Clinical Immunology Communications
JF - Clinical Immunology Communications
ER -