Roxane Labrosse1, Sara Barmettler2, Beata Derfalvi3, Annaliesse Blincoe4, Guilhem Cros5, Jonathan Lacombe-Barrios6, Julie Barsalou6, Nancy Yang2, Nora Alrumayyan3, Jan Sinclair4, Mei-Sing Ong7, Carlos A Camargo8, Jolan Walter9, Elie Haddad10. 1. Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada; Division of Hematology-Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, Mass. 2. Allergy and Clinical Immunology Unit, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass. 3. Division of Immunology, Department of Pediatrics, IWK Health Center, Dalhousie University, Halifax, Nova Scotia, Canada. 4. Department of Paediatric Immunology and Allergy, Starship Children's Hospital, Auckland, New Zealand. 5. Centre Hospitalier de l'Universite de Montreal, University of Montreal, Montreal, Quebec, Canada. 6. Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada. 7. Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care, Boston, Mass. 8. Allergy and Clinical Immunology Unit, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass; Department of Emergency Medicine, Massachusetts General Hospital, Boston, Mass. 9. Department of Pediatrics, University of South Florida at Johns Hopkins All Children's Hospital, Tampa, Fla; Pediatric Allergy and Immunology, Massachusetts General Hospital, Boston, Mass. 10. Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada; Department of Microbiology, Infectiology and Immunology, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada. Electronic address: elie.haddad@umontreal.ca.
Abstract
BACKGROUND: Rituximab is a B-cell depleting agent used in B-cell malignancies and autoimmune diseases. A subset of adult patients may develop prolonged and symptomatic hypogammaglobulinemia following rituximab treatment. However, this phenomenon has not been well delineated in the pediatric population. OBJECTIVES: This study sought to determine the prevalence, risk factors, and clinical significance of hypogammaglobulinemia following rituximab therapy in children. METHODS: This was a multicenter, retrospective cohort study that extracted clinical and immunological data from pediatric patients who received rituximab. RESULTS: The cohort comprised 207 patients (median age, 12.0 years). Compared to baseline values, there was a significant increase in hypogammaglobulinemia post-rituximab therapy, with an increase in prevalence of hypo-IgG (28.7%-42.6%; P = .009), hypo-IgA (11.1%-20.4%; P = .02), and hypo-IgM (20.0%-62.0%; P < .0001). Additionally, low IgG levels at any time post-rituximab therapy were associated with a higher risk of serious infections (34.4% vs 18.9%; odds ratio, 2.3; 95% CI, 1.1-4.8; P = .03). Persistent IgG hypogammaglobulinemia was observed in 27 of 101 evaluable patients (26.7%). Significant risk factors for persistent IgG hypogammaglobulinemia included low IgG and IgA levels pre-rituximab therapy. Nine patients (4.3%) within the study were subsequently diagnosed with a primary immunodeficiency, 7 of which received rituximab for autoimmune cytopenias. CONCLUSIONS: Hypogammaglobulinemia post-rituximab treatment is frequently diagnosed within the pediatric population. Low IgG levels are associated with a significant increase in serious infections, and underlying primary immunodeficiencies are relatively common in children receiving rituximab, thus highlighting the importance of immunologic monitoring both before and after rituximab therapy.
BACKGROUND:Rituximab is a B-cell depleting agent used in B-cell malignancies and autoimmune diseases. A subset of adult patients may develop prolonged and symptomatic hypogammaglobulinemia following rituximab treatment. However, this phenomenon has not been well delineated in the pediatric population. OBJECTIVES: This study sought to determine the prevalence, risk factors, and clinical significance of hypogammaglobulinemia following rituximab therapy in children. METHODS: This was a multicenter, retrospective cohort study that extracted clinical and immunological data from pediatric patients who received rituximab. RESULTS: The cohort comprised 207 patients (median age, 12.0 years). Compared to baseline values, there was a significant increase in hypogammaglobulinemia post-rituximab therapy, with an increase in prevalence of hypo-IgG (28.7%-42.6%; P = .009), hypo-IgA (11.1%-20.4%; P = .02), and hypo-IgM (20.0%-62.0%; P < .0001). Additionally, low IgG levels at any time post-rituximab therapy were associated with a higher risk of serious infections (34.4% vs 18.9%; odds ratio, 2.3; 95% CI, 1.1-4.8; P = .03). Persistent IgG hypogammaglobulinemia was observed in 27 of 101 evaluable patients (26.7%). Significant risk factors for persistent IgG hypogammaglobulinemia included low IgG and IgA levels pre-rituximab therapy. Nine patients (4.3%) within the study were subsequently diagnosed with a primary immunodeficiency, 7 of which received rituximab for autoimmune cytopenias. CONCLUSIONS:Hypogammaglobulinemia post-rituximab treatment is frequently diagnosed within the pediatric population. Low IgG levels are associated with a significant increase in serious infections, and underlying primary immunodeficiencies are relatively common in children receiving rituximab, thus highlighting the importance of immunologic monitoring both before and after rituximab therapy.
Authors: Clara Franco-Jarava; Irene Valenzuela; Jacques G Riviere; Marina Garcia-Prat; Mónica Martínez-Gallo; Romina Dieli-Crimi; Neus Castells; Laura Batlle-Masó; Pere Soler-Palacin; Roger Colobran Journal: Front Immunol Date: 2022-06-17 Impact factor: 8.786