Ottaviano Giorgio, Marinoni Maddalena, Graziani Simona, Sibson Keith, Barzaghi Federica, Bertolini Patrizia, Chini Loredana, Corti Paola, Cancrini Caterina, D'Alba Irene, Gabelli Maria, Gallo Vera, Giancotta Carmela, Giordano Paola, Lassandro Giuseppe, Martire Baldassare, Angarano Rosa, Mastrodicasa Elena, Bava Cecilia, Miano Maurizio, Naviglio Samuele, Verzegnassi Federico, Saracco Paola, Trizzino Antonino, Biondi Andrea, Pignata Claudio, Moschese Viviana
Paediatric Haematology, Milano-Bicocca University, Monza, Italy.
Paediatric Department, ASST-Sette Laghi, "F. Del Ponte" Hospital, Varese, Italy.
J Allergy Clin Immunol Pract. 2020 Jan;8(1):273-282. doi: 10.1016/j.jaip.2019.07.032. Epub 2019 Aug 2.
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.
To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use.
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.
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.
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.
利妥昔单抗（RTX；抗CD20单克隆抗体）是治疗难治性免疫性血小板减少症、自身免疫性溶血性贫血（AHA）和伊文氏综合征（ES）患儿的一种治疗选择。这些患者中RTX诱导的低丙种球蛋白血症的患病率和临床病程鲜为人知。
评估RTX使用后持续性低丙种球蛋白血症（PH）的患病率和危险因素。
从16个意大利中心和1个英国中心收集接受RTX治疗免疫性血小板减少症、AHA和ES患儿的临床和免疫学数据，时间点为RTX治疗前（0）、+6个月以及每年一次，直至RTX治疗后4年。排除先前诊断为恶性肿瘤或原发性免疫缺陷（PID）的患者。
我们分析了53例接受RTX治疗的免疫性血小板减少症患儿（n = 36）、AHA患儿（n = 13）和ES患儿（n = 4）。中位随访时间为30个月（范围12 - 48个月）。32%（53例中的17例）的患者出现PH，定义为末次随访时（RTX治疗后>12个月）IgG水平低于年龄相关的2个标准差。出现PH的患儿观察到B细胞恢复明显延迟（风险比，0.55；P <.05），17例患者中有6例（35%）在末次随访时仍有未解决的B细胞淋巴细胞减少。PH与IgA和IgM缺乏、RTX使用时年龄较小（51个月对116个月；P <.01）、AHA/ES诊断以及对RTX反应较好有关。9例PH患者（17例中的9例[53%]）最终被诊断为PID。
RTX治疗后PH在自身免疫性血细胞减少症患儿中很常见；相当一部分RTX治疗后PH患者最终被诊断为PID。因此，建议对这些患者进行PID的深入调查。
