多中心72例噬血细胞综合征诊疗分析

目的 提高对噬血细胞综合征(HPS)的认识和诊断水平,探索对该病的有效治疗手段.方法 对多中心72例HPS患者的病因、临床表现、实验室检查指标、治疗方案及临床转归进行回顾性分析.结果 72例患者原发病以病毒感染和T细胞淋巴瘤居多.主要临床表现以持续高热(100%)、脾肿大(83.3%)最为多见.发热(100%)、外周血两系及以上血细胞减低(97.2%)、血清可溶性IL-2受体(Scd25)水平升高(93.1%)以及NK细胞活性降低(94.4%)在诊断中的灵敏度较高.实验室检查发现HPS患者组血清糖化铁蛋白百分比为(17.4±16.0)%.明显低于正常对照的(53.6±13.3)%.而血清TNF-α水平为(143.2±64.8) μg/L,明显高于正常对照的(66.9±19.4) μg/L.多数HPS患者存在肝功能损害(83.6%),以AST升高及低白蛋白血症为主.47例经治HPS患者15周总体生存率为46.8%,其中27例氟达拉滨联合大剂量激素治疗HPS患者总体生存率达63.0%.死亡组患者的血小板计数和纤维蛋白原水平明显低于存活组(P＜0.01).结论 HPS可由多种病因所致,临床表现多样.发热、外周血两系及以上血细胞减低、血清Scd25水平升高以及NK细胞活性降低在诊断中的灵敏度较高.糖化铁蛋白百分比、血清TNF-α水平的变化有助于诊断HPS.氟达拉滨联合大剂量激素是有效的治疗方案.血小板计数和纤维蛋白原水平降低是疾病的不良预后因素.

A multicenter retrospective analysis of diagnosis and treatment of 72 hemophagocytic syndrome patients

Objective To explore early diagnosis of hemophagocytic syndrome (HPS) and effective treatment. Methods A multicenter retrospective study was carried out to analyze the causes, clinical features , laboratory findings, treatment and clinical outcomes of 72 patients with HPS. Results Among the 72 patients, EBV infection and T lymphoma were the most common initiating diseases. The most common clinical features were persistent fever (100% ) and splenomegaly (83. 3% ). The diagnostic sensitivity was persistent fever (100% ), peripheral cytopenia in two or more lineages (97.2% ) , high concentration of serum soluble CD25 (93.1% ) and low NK cell activity (94. 4% ). The median percentage of serum glycosylated ferritin was significantly lower in patients in HPS group [(17.4 ± 16. 0)%] than in control group [ (53. 6 ± 13.3)%] (P＜0. 01). And the median level of serum TNF-α was significantly higher in patients group [(143.2 ± 64.8) μg/L] than in controls [(66.9 ±19.4) μg/L] (P＜0.01). Hepatic dysfunction was seen in most patients (83.6% ) mainly manifested as elevated liver enzymes and hypoalbuminemia. The 15-week total survival rate was 46. 8% in 47 treated patients, and was 63% in 27 treated with fludarabine in combination with high dose methylprednisolone. The platelet count and fibrinogen level were significantly lower in death group than in survival group. Conclusions The diagnostic sensitivities of presistent fever, peripheral cytopenia in two or more lineages, high concentration of serum soluble CD25 and low NK cell activity are relatively high and lacking hemophagocytosis does not exclude the diagnosis. Low percentage of glycosylated ferritin and high concentration of TNF-α would be helpful to the diagnosis. High dose methylprednisolone combined with fludarabine is an effective therapy. Platelet count and fibrinogen level are poor prognostic factors for HPS.