Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore, Singapore.
Department of Paediatric Haematology Oncology, KK Women's and Children's Hospital, Singapore, Singapore.
Pediatr Blood Cancer. 2023 Mar;70(3):e30122. doi: 10.1002/pbc.30122. Epub 2022 Dec 29.
Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine overall mortality of critically ill children with HLH, and describes etiologies, treatment, and pediatric intensive care unit (PICU) support employed.
PubMed, Embase, Web of Science, CINAHL, and Cochrane Library from inception until February 28, 2022.
Observational studies and randomized controlled trials reporting children aged 18 years or below, diagnosed with HLH and admitted to the PICU.
Etiologies, treatment modalities, PICU therapies, and mortality outcomes were summarized. Random-effects meta-analysis was performed.
Total 36 studies (total patients = 493, mean age: 49.5 months [95% confidence interval (CI): 30.9-79.5]) were included. Pooled mortality rate was 32.6% (95% CI: 23.4-42.4). The most frequent etiologies for HLH were infections (53.3%) and primary HLH (12.8%), while the remaining cases were due to other causes of secondary HLH, including autoimmune diseases, malignancy, and drug-induced and idiopathic HLH. Pooled mortality rate was higher in primary than secondary HLH (72.2%, 95% CI: 57.8-84.5 vs. 23.9%, 95% CI: 14.4-35.02; p < .01). Univariate analysis found that treatment with etoposide was associated with higher mortality, while intravenous immunoglobulins (IVIGs) were associated with lower mortality. Conversely, multivariable analysis adjusted for etiology demonstrated no association between etoposide and IVIG use, and mortality. Twenty-one studies (total patients = 278) had detailed information on PICU therapies. Mechanical ventilation (MV), continuous renal replacement therapy, and inotropes were used in 107 (38.5%), 66 (23.7%), and 51 patients (18.3%), respectively. Need for MV was associated with increased risk of mortality (mean difference = 28%, 95% CI: 9-47).
Critically ill children with HLH have high mortality rates and require substantial PICU support. Collaborative work between multiple centers with standardized data collection can potentially provide more robust data.
噬血细胞性淋巴组织细胞增生症（HLH）危重症患儿的死亡危险因素尚未得到充分描述。本系统评价旨在确定危重症 HLH 患儿的总体死亡率，并描述病因、治疗方法以及儿科重症监护病房（PICU）的支持措施。
从建库至 2022 年 2 月 28 日，PubMed、Embase、Web of Science、CINAHL 和 Cochrane Library。
观察性研究和随机对照试验，纳入年龄在 18 岁及以下、诊断为 HLH 并入住 PICU 的患儿。
总结病因、治疗方式、PICU 治疗和死亡率结局。采用随机效应荟萃分析。
共纳入 36 项研究（总患者=493 例，平均年龄：49.5 个月[95%置信区间（CI）：30.9-79.5]）。汇总死亡率为 32.6%（95%CI：23.4-42.4）。HLH 最常见的病因是感染（53.3%）和原发性 HLH（12.8%），其余病例则由继发性 HLH 的其他病因引起，包括自身免疫性疾病、恶性肿瘤、药物诱导和特发性 HLH。原发性 HLH 的死亡率高于继发性 HLH（72.2%，95%CI：57.8-84.5 比 23.9%，95%CI：14.4-35.02；p<0.01）。单因素分析发现依托泊苷治疗与死亡率升高相关，而静脉注射免疫球蛋白（IVIG）与死亡率降低相关。相反，多变量分析调整病因后，依托泊苷和 IVIG 的使用与死亡率之间无关联。21 项研究（总患者=278 例）详细记录了 PICU 治疗信息。107 例（38.5%）、66 例（23.7%）和 51 例（18.3%）患儿分别接受了机械通气（MV）、连续肾脏替代治疗和正性肌力药物治疗。需要 MV 与死亡率升高相关（平均差异=28%，95%CI：9-47）。
危重症 HLH 患儿死亡率较高，需要大量 PICU 支持。多中心间开展协作并进行标准化数据收集，可能会提供更可靠的数据。
