Rituximab-induced Hypogammaglobulinemia and Infection Risk in Pediatric Patients.

BACKGROUND Rituximab (RTX) 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 RTX. However, this phenomenon has not been well delineated in the pediatric population. OBJECTIVE To determine the prevalence, risk factors and clinical significance of hypogammaglobulinemia following RTX therapy in children. METHODS We conducted a multi-center, retrospective cohort study and extracted clinical and immunological data from pediatric patients who received RTX. RESULTS The cohort was comprised of 207 patients (median age 12.0 years). Compared to baseline values, there was a significant increase in hypogammaglobulinemia post-RTX, with an increase in prevalence of hypo-IgG (28.7% to 42.6%, p=0.009), hypo-IgA (11.1% to 20.4%, p=0.02) and hypo-IgM (20.0% to 62.0%, p<0.0001). Additionally, low IgG levels at any time post-RTX were associated with a higher risk of serious infections (34.4% vs 18.9%; OR 2.3, 95% CI 1.1-4.8, p=0.03). Persistent IgG hypogammaglobulinemia (PH-IgG) was observed in 27 (26.7%) of 101 evaluable patients. Significant risk factors for PH-IgG included low IgG and IgA levels pre-RTX. Nine patients (4.3%) within the study were subsequently diagnosed with a primary immunodeficiency (PID), seven of which received RTX for autoimmune cytopenias. CONCLUSION Hypogammaglobulinemia post-RTX is frequently diagnosed within the pediatric population. Low IgG levels are associated with a significant increase in serious infections, and underlying PIDs are relatively common in children receiving RTX, thus highlighting the importance of immunologic monitoring both before and after RTX therapy.