Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome that may complicate hematologic malignancies (HMs). The appropriateness of current criteria for diagnosing HLH in the context of HMs is unknown because they were developed for children with familial HLH (HLH-2004) or derived from adult patient cohorts in which HMs were underrepresented (HScore). Moreover, many features of these criteria may directly reflect the underlying HM rather than an abnormal inflammatory state. To improve and potentially simplify HLH diagnosis in patients with HMs, we studied an international cohort of 225 adult patients with various HMs both with and without HLH and for whom HLH-2004 criteria were available. Classification and regression tree and receiver-operating curve analyses were used to identify the most useful diagnostic and prognostic parameters and to optimize laboratory cutoff values. Combined elevation of soluble CD25 (>3900 U/mL) and ferritin (>1000 ng/mL) best identified HLH-2004-defining features (sensitivity, 84%; specificity, 81%). Moreover, this combination, which we term the optimized HLH inflammatory (OHI) index, was highly predictive of mortality (hazard ratio, 4.3; 95% confidence interval, 3.0-6.2) across diverse HMs. Furthermore, the OHI index identified a large group of patients with high mortality risk who were not defined as having HLH according to HLH-2004/HScore. Finally, the OHI index shows diagnostic and prognostic value when used for routine surveillance of patients with newly diagnosed HMs as well as those with clinically suspected HLH. Thus, we conclude that the OHI index identifies patients with HM and an inflammatory state associated with a high mortality risk and warrants further prospective validation.

中文翻译：

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恶性肿瘤相关噬血细胞性淋巴组织细胞增多症诊断和死亡率预测的改进指数。

噬血细胞性淋巴组织细胞增多症 (HLH) 是一种危及生命的炎症综合征，可能使血液系统恶性肿瘤 (HMs) 复杂化。目前在 HM 背景下诊断 HLH 的标准是否合适尚不清楚，因为这些标准是针对家族性 HLH 儿童 (HLH-2004) 制定的，或者源自 HM 代表性不足的成年患者队列 (HScore)。此外，这些标准的许多特征可能直接反映潜在的 HM，而不是异常的炎症状态。为了改善并可能简化 HM 患者的 HLH 诊断，我们研究了一个由 225 名患有各种 HM 的成人患者组成的国际队列，这些患者有或没有 HLH，并且可以使用 HLH-2004 标准。分类和回归树以及受试者工作曲线分析用于确定最有用的诊断和预后参数并优化实验室截止值。可溶性 CD25 (>3900 U/mL) 和铁蛋白 (>1000 ng/mL) 的联合升高最能确定 HLH-2004 定义特征（敏感性，84%；特异性，81%）。此外，这种组合，我们称之为优化的 HLH 炎症 (OHI) 指数，可以高度预测不同 HM 的死亡率（风险比，4.3；95% 置信区间，3.0-6.2）。此外，OHI 指数确定了一大群具有高死亡风险的患者，根据 HLH-2004/HScore，这些患者未被定义为患有 HLH。最后，OHI 指数在用于新诊断 HM 患者以及临床疑似 HLH 患者的常规监测时显示出诊断和预后价值。因此，我们得出结论，OHI 指数可识别 HM 和与高死亡风险相关的炎症状态患者，并值得进一步前瞻性验证。