Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party
Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party
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DOI：
10.1111/ejh.12399
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Seo, Jong Jin
中科院分区：
文献类型：
--
作者：
Koh, Kyung-Nam;Im, Ho Joon;Seo, Jong Jin
背景我们分析了韩国全国范围内的儿童噬血细胞性淋巴组织细胞增生症（HLH）患者的登记资料，以评估儿童HLH的临床和遗传特征以及治疗结果。MethodsThe Korea Histiocytosis Working Party回顾性分析了1996年至2011年间诊断为HLH的251例儿童患者的数据。64例推测患有继发性HLH，162例患有未具体说明的HLH。在217名可评估患者中，91名（42%）伴有EB病毒感染。在238例可评估的患者中，81例（34%）明显累及中枢神经系统（CNS），这在家族性组中更常见。基因检测显示，UNC 13 D突变占主导地位，两个复发性剪接突变（c.118- 308 C>T和c.754-1G>C）的发生率很高。5年总生存率为68%（家族性组为38%，假定继发性组为81%）。32例异基因造血干细胞移植患者的5年总生存率为64%。在多变量分析中，诊断时年龄较小、严重的转氨酶血症和凝血功能异常是生存的独立预后因素。在最初的治疗反应也是显着的指标outcome.ConclusionOur的研究表明，独特的优势UNC 13 D突变和脆弱性，爱泼斯坦-巴尔病毒感染的韩国儿童HLH，并强调年龄，肝功能障碍，在这种疾病的治疗反应的预后意义。一个多中心的前瞻性试验，建立在目前的结果是必要的，以确定亚组的患者预后不良，并确定最佳的治疗。
BackgroundWe analyzed a nationwide registry of pediatric patients with hemophagocytic lymphohistiocytosis (HLH) in Korea to assess the clinical and genetic features and treatment outcomes in pediatric HLH.MethodsThe Korea Histiocytosis Working Party retrospectively analyzed data on 251 pediatric patients diagnosed with HLH between 1996 and 2011.ResultsIn the study cohort, 25 cases were categorized with familial HLH, 64 with presumed secondary HLH, and 162 with unspecified HLH. Of 217 evaluable patients, 91 (42%) had concomitant Epstein-Barr virus infection. Of 238 evaluable patients, central nervous system (CNS) involvement, which was more frequent in the familial group, was evident in 81 cases (34%). Genetic tests revealed a predominant UNC13D mutation with a high incidence of two recurrent splicing mutations (c.118-308C>T and c.754-1G>C). The 5-yr overall survival rate was 68% (38% in the familial group and 81% in the presumed secondary group). The 5-yr overall survival rate among 32 patients who underwent allogeneic hematopoietic stem cell transplantation was 64%. In multivariate analysis, a younger age at diagnosis, severe transaminasemia, and a coagulation abnormality were independent prognostic factors for survival. Responses during initial treatments were also significant indicators of outcome.ConclusionOur study showed the unique predominance of a UNC13D mutation and vulnerability to Epstein-Barr virus infection in Korean children with HLH and emphasizes the prognostic significance of age, liver dysfunction, and treatment responses in this disease. A multicenter prospective trial that builds on the present results is warranted to identify subgroups of patients with a poor prognosis and identify optimal treatments.