Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

J Allergy Clin Immunol Pract. 2020 Jan;8(1):273-282. doi: 10.1016/j.jaip.2019.07.032. Epub 2019 Aug 2.

Abstract

Background: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known.

Objective: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use.

Methods: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded.

Results: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID.

Conclusions: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients.

Keywords: Autoimmunity; Cytopenia; Hypogammaglobulinemia; Primary immunodeficiency; Rituximab.

MeSH terms

  • Agammaglobulinemia* / drug therapy
  • Agammaglobulinemia* / epidemiology
  • Anemia, Hemolytic, Autoimmune* / drug therapy
  • Anemia, Hemolytic, Autoimmune* / epidemiology
  • Child
  • Humans
  • Purpura, Thrombocytopenic, Idiopathic* / drug therapy
  • Purpura, Thrombocytopenic, Idiopathic* / epidemiology
  • Rituximab / therapeutic use
  • Thrombocytopenia*
  • Treatment Outcome

Substances

  • Rituximab