Labrosse Roxane, Barmettler Sara, Derfalvi Beata, Blincoe Annaliesse, Cros Guilhem, Lacombe-Barrios Jonathan, Barsalou Julie, Yang Nancy, Alrumayyan Nora, Sinclair Jan, Ong Mei-Sing, Camargo Carlos A, Walter Jolan, Haddad Elie
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.
Allergy and Clinical Immunology Unit, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass.
J Allergy Clin Immunol. 2021 Aug;148(2):523-532.e8. doi: 10.1016/j.jaci.2021.03.041. Epub 2021 Apr 20.
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.
This study sought to determine the prevalence, risk factors, and clinical significance of hypogammaglobulinemia following rituximab therapy in children.
This was a multicenter, retrospective cohort study that extracted clinical and immunological data from pediatric patients who received rituximab.
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.
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.
利妥昔单抗是一种用于治疗B细胞恶性肿瘤和自身免疫性疾病的B细胞清除剂。一部分成年患者在接受利妥昔单抗治疗后可能会出现持续且有症状的低丙种球蛋白血症。然而，这一现象在儿科人群中尚未得到充分描述。
本研究旨在确定儿童接受利妥昔单抗治疗后低丙种球蛋白血症的患病率、危险因素及临床意义。
这是一项多中心回顾性队列研究，从接受利妥昔单抗治疗的儿科患者中提取临床和免疫学数据。
该队列包括207例患者（中位年龄12.0岁）。与基线值相比，利妥昔单抗治疗后低丙种球蛋白血症显著增加，低IgG血症患病率升高（28.7%-42.6%；P = 0.009），低IgA血症患病率升高（11.1%-20.4%；P = 0.02），低IgM血症患病率升高（20.0%-62.0%；P < 0.0001）。此外，利妥昔单抗治疗后任何时间的低IgG水平都与严重感染风险较高相关（34.4%对18.9%；比值比，2.3；95% CI，1.1-4.8；P = 0.03）。在101例可评估患者中有27例（26.7%）观察到持续性IgG低丙种球蛋白血症。持续性IgG低丙种球蛋白血症的显著危险因素包括利妥昔单抗治疗前的低IgG和IgA水平。该研究中有9例患者（4.3%）随后被诊断为原发性免疫缺陷，其中7例因自身免疫性血细胞减少接受利妥昔单抗治疗。
利妥昔单抗治疗后低丙种球蛋白血症在儿科人群中经常被诊断出来。低IgG水平与严重感染显著增加相关，并且潜在的原发性免疫缺陷在接受利妥昔单抗治疗的儿童中相对常见，因此突出了利妥昔单抗治疗前后免疫监测的重要性。
