Hypogammaglobulinemia and bacterial infections following pediatric post-transplant lymphoproliferative disorder in the rituximab era.

Abstract

Treatment of PTLD using immune-depleting agents such as RTX may be associated with increased risk of infections. The aim of this report was to describe the incidence of hypogammaglobulinemia and bacterial infections in children with PTLD after SOT at a single center since the introduction of RTX. A retrospective review was conducted over a study period of 2000-2016 in pediatric patients diagnosed with biopsy-proven PTLD based on the WHO histologic criteria. Hypogammaglobulinemia was defined by serum IgG <4g/L; CPBI was defined by clinically significant infection by an identified pathogenic bacteria isolated from a normally sterile body site. Twenty-eight patients were included, comprising 16 LTx and 12 ITx patients, and 17 patients received RTX therapy. Total of 31 episodes of CPBI occurred in 16 patients. Incidence of CPBI was 31.4 infections per 100 patient-years in RTX-treated patients, as compared to 8.4 infections per 100 patient-years in non-RTX-treated patients (P<0.001). Hypogammaglobulinemia was significantly more prevalent after 6months (P=0.001) and 2years (P=0.005) in RTX-treated patients, as compared to none in the group that did not receive RTX. Hypogammaglobulinemia (P=0.047), ITx (P=0.027), and monomorphic PTLD (P=0.024) were significantly associated with recurrent (≥2) CPBI and/or CPBI-related deaths within the first year post-PTLD. While RTX is an effective treatment for PTLD, hypogammaglobulinemia can persist for up to 2years following RTX therapy, which may be associated with the higher cumulative rates of CPBI observed in RTX-treated patients.