Persistent hypogammaglobulinemia after rituximab therapy in pediatric patients, prevalence and clinical outcomes: Hypogammaglobulinemia after rituximab in children Journal Article
| Authors: | Höppener, S. P. C.; Veldkamp, S. R.; de Groot, M. C. H.; Haitjema, S.; Drylewicz, J.; Boelens, J. J.; Lindemans, C. A.; van Montfrans, J.; van Royen-Kerkhof, A.; Jansen, M. H. A. |
| Article Title: | Persistent hypogammaglobulinemia after rituximab therapy in pediatric patients, prevalence and clinical outcomes: Hypogammaglobulinemia after rituximab in children |
| 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. © 2025 |
| Keywords: | child; controlled study; major clinical study; prednisone; methotrexate; rituximab; antineoplastic agent; multiple cycle treatment; protein kinase inhibitor; incidence; prevalence; cohort analysis; alkylating agent; cyclophosphamide; dexamethasone; immunoglobulin; recurrent infection; hematopoietic stem cell transplantation; retrospective study; pediatric; b lymphocyte; drug fatality; hematologic malignancy; immunoglobulin g; graft versus host reaction; disease duration; azathioprine; immunomodulating agent; hydrocortisone; immunoglobulin class switching; immune deficiency; corticosteroid; autoimmune disease; tacrolimus; immunoglobulin blood level; antineoplastic antimetabolite; bacterial infection; immunoglobulin deficiency; everolimus; enteropathy; sirolimus; cyclosporine; nephrotic syndrome; immunosuppressive agent; longitudinal study; thymocyte antibody; abatacept; immunoglobulin m; triamcinolone; immune reconstitution; clinical outcome; infliximab; mycophenolic acid; adalimumab; tocilizumab; leflunomide; hypogammaglobulinemia; human; male; female; article; tertiary care center; substitution therapy; disease modifying antirheumatic drug; memory b lymphocyte; sinopulmonary infection; b cell reconstitution; cd19+ b lymphocyte; cd19+ cd27+ immunoglobulin g+ switched memory b lymphocyte; persistent hypogammaglobulinemia |
| Journal Title: | Clinical Immunology Communications |
| Volume: | 7 |
| ISSN: | 2772-6134 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-06-01 |
| Start Page: | 55 |
| End Page: | 63 |
| Language: | English |
| DOI: | 10.1016/j.clicom.2025.04.001 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
