Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
Acta Paediatr. 2012 Mar;101(3):313-8. doi: 10.1111/j.1651-2227.2011.02501.x. Epub 2011 Nov 17.
Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening disturbance of immunoregulation. HLH comprises primary and acquired forms with different disease severity. A large proportion of deaths occur early into treatment. We investigated association with early death for laboratory and clinical parameters before the start of and 2 weeks into therapy.
A total of 232 children from Scandinavia, Germany or Italy, fulfilling diagnostic criteria and/or with familial disease and/or HLH-causing mutations, receiving HLH treatment 1994-2008 were included. The relation between clinical findings and early pre-transplant death was examined using the Cox proportional hazards model, with a 4-month right-truncation of the outcome. Patients were censored at last follow-up or transplant. Statistically significant predictors were adjusted for sex, age and each other.
The following features were significantly associated with adverse outcome: hyperbilirubinaemia (>50 μmol/L; adjusted hazard ratio (aHR) 3.2; 95% confidence interval 1.3-8.1, p = 0.011), hyperferritinaemia (>2000 μg/L; aHR 3.2; 1.2-8.6, p = 0.019), cerebrospinal fluid pleocytosis (>100 × 10(6) /L; aHR 5.1; 1.4-18.5, p = 0.012) at diagnosis, and thrombocytopenia (<40 × 10(9) /L; aHR 3.4; 1.1-10.7, p = 0.033), and hyperferritinaemia (>2000 μg/L; aHR 10.6; 1.2-96.4, p = 0.037) 2 weeks into therapy. Non-improvement of fever, anaemia and/or thrombocytopenia also had adverse impact.
There seem to be easily available clinical predictors of early mortality in HLH patients, which may help guide treatment decisions.
噬血细胞性淋巴组织细胞增生症（HLH）是一种危及生命的免疫调节紊乱。HLH 包括原发性和获得性两种形式，疾病严重程度不同。很大一部分死亡发生在治疗早期。我们研究了在开始治疗前和治疗 2 周时的实验室和临床参数与早期死亡的相关性。
共纳入 232 名来自斯堪的纳维亚、德国或意大利的儿童，符合诊断标准和/或家族性疾病和/或导致 HLH 的突变，于 1994 年至 2008 年接受 HLH 治疗。使用 Cox 比例风险模型检查临床发现与早期移植前死亡的关系，结果进行了 4 个月的右截断。患者在最后一次随访或移植时被删失。有统计学意义的预测因素在性别、年龄和彼此之间进行了调整。
以下特征与不良结局显著相关：高胆红素血症（>50 μmol/L；调整后的危险比[aHR]3.2；95%置信区间 1.3-8.1，p = 0.011）、高铁蛋白血症（>2000 μg/L；aHR 3.2；1.2-8.6，p = 0.019）、诊断时脑脊液白细胞增多（>100 × 10^6/L；aHR 5.1；1.4-18.5，p = 0.012），血小板减少症（<40 × 10^9/L；aHR 3.4；1.1-10.7，p = 0.033），以及治疗 2 周时高铁蛋白血症（>2000 μg/L；aHR 10.6；1.2-96.4，p = 0.037）。发热、贫血和/或血小板减少症无改善也有不良影响。
HLH 患者似乎有容易获得的早期死亡临床预测因素，这可能有助于指导治疗决策。
