OBJECTIVE To assess the benefit of the recombinant human interleukin-1 receptor antagonist anakinra in treating pediatric patients with secondary hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) associated with rheumatic and nonrheumatic conditions. METHODS A retrospective chart review of all anakinra-treated patients with secondary HLH/MAS was performed at Children's of Alabama from January 2008 through December 2016. Demographic, clinical, laboratory, and genetic characteristics, outcomes data, and information on concurrent treatments were collected from the records and analyzed using appropriate univariate statistical approaches to assess changes following treatment and associations between patient variables and outcomes. RESULTS Forty-four patients with secondary HLH/MAS being treated with anakinra were identified in the electronic medical records. The median duration of hospitalization was 15 days. The mean pretreatment serum ferritin level was 33,316 ng/ml and dropped to 14,435 ng/ml (57% decrease) within 15 days of the start of anakinra treatment. The overall mortality rate in the cohort was 27%. Earlier initiation of anakinra (within 5 days of hospitalization) was associated with reduced mortality (P = 0.046), whereas thrombocytopenia (platelet count <100,000/μl) and STXBP2 mutations were both associated with increased mortality (P = 0.008 and P = 0.012, respectively). In considering patients according to their underlying diagnosis, those with systemic juvenile idiopathic arthritis (JIA) had the lowest mortality rate, with no deaths among the 13 systemic JIA patients included in the study (P = 0.006). In contrast, those with an underlying hematologic malignancy had the highest mortality rate, at 100% (n = 3). CONCLUSION These findings suggest that anakinra appears to be effective in treating pediatric patients with non-malignancy-associated secondary HLH/MAS, especially when it is given early in the disease course and when administered to patients who have an underlying rheumatic disease.

中文翻译：

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Anakinra在治疗小儿继发性吞噬性淋巴细胞增多症中的作用。

目的评估重组人白细胞介素1受体拮抗剂阿那卡那在治疗风湿病和非风湿病性继发性吞噬性淋巴细胞组织细胞增生症（HLH）/巨噬细胞活化综合征（MAS）的儿科患者中的益处。方法从2008年1月至2016年12月，在阿拉巴马州儿童医院对所有接受anakinra治疗的继发性HLH / MAS患者进行回顾性图表回顾。记录并使用适当的单变量统计方法进行分析，以评估治疗后的变化以及患者变量与结果之间的关联。结果在电子病历中确定了44例接受过类似烟碱治疗的继发性HLH / MAS患者。中位住院时间为15天。anakinra治疗开始后的15天内，平均血清铁蛋白预处理水平为33,316 ng / ml，降至14435 ng / ml（下降57％）。该队列的总死亡率为27％。anakinra的早期发作（住院5天之内）与死亡率降低相关（P = 0.046），而血小板减少症（血小板计数<100,000 /μl）和STXBP2突变均与死亡率升高相关（P = 0.008和P = 0.012，分别）。在根据潜在诊断考虑患者时，患有系统性幼年特发性关节炎（JIA）的患者死亡率最低，研究纳入的13例系统性JIA患者中无死亡（P = 0.006）。相反，具有潜在血液学恶性肿瘤的患者死亡率最高，为100％（n = 3）。结论这些发现表明，anakinra似乎可有效治疗非恶性肿瘤相关性继发性HLH / MAS患儿，特别是在疾病过程的早期给予和对有潜在风湿病的患者给药时。