Laboratory of Hematologic Diseases, Hematology Center, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56, Nanlishi Road, Xicheng District, Beijing, 100045, China.
Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
Ann Hematol. 2024 Jan;103(1):17-28. doi: 10.1007/s00277-023-05499-6. Epub 2023 Oct 18.
To analyze the genetic variation and prognosis of primary hemophagocytic lymphohistiocytosis (pHLH) in children and the clinical features of isolated central nervous system HLH (CNS-HLH). We retrospectively analyzed the clinical and genetic data of 480 HLH children admitted to our hospital from September 2017 to September 2022. There were 66 patients (13.75%) with pHLH, and the median age was 3.21 years (0.17-12.92 years). Variants in UNC13D (22/66, 33.33%), PRF1 (20/66, 30.30%) and XIAP (11/66, 16.67%) were the most common. More CNS involvement was observed in pHLH patients than in secondary hemophagocytic lymphohistiocytosis (sHLH) patients (50% vs. 25.3%, P = 0.001). Eight pHLH patients had isolated CNS-HLH at onset, which progressed to systemic HLH within 10-30 days to several years. Among them, five patients who underwent hematopoietic stem cell transplantation (HSCT) survived without CNS sequelae, and the three patients who did not undergo HSCT died of disease progression or recurrence. Determination of natural killer (NK) cell cytotoxicity and CD107a levels had low sensitivity and specificity in the diagnosis of pHLH, especially in patients with PRF1 and XIAP mutations. The 3-year overall survival (OS) was significantly lower in pHLH patients than in sHLH patients (74.5% ± 14.7% vs. 89.2% ± 3.53%, P = 0.021) and in patients with CNS involvement than in those without (53.8% ± 26.07% vs. 94.4% ± 10.58%, P = 0.012). There was a significant difference in OS among pHLH patients with different gene variants (P = 0.032); patients with PRF1 variants had poor 3-year OS, and patients with XIAP variants had good 3-year OS (50% ± 28.22% and 100%, respectively). pHLH patients with distinct variants have different prognoses. Isolated CNS-HLH patients are easily misdiagnosed, and HSCT may be beneficial for these patients. Determination of NK cell cytotoxicity and CD107a levels cannot precisely distinguish pHLH from sHLH.
分析儿童原发性噬血细胞性淋巴组织细胞增生症（pHLH）的遗传变异和预后，以及孤立性中枢神经系统噬血细胞性淋巴组织细胞增生症（CNS-HLH）的临床特征。方法：回顾性分析 2017 年 9 月至 2022 年 9 月我院收治的 480 例噬血细胞性淋巴组织细胞增生症患儿的临床和遗传资料。其中 66 例（13.75%）为 pHLH，中位年龄 3.21 岁（0.17-12.92 岁）。UNC13D（22/66，33.33%）、PRF1（20/66，30.30%）和 XIAP（11/66，16.67%）变异最为常见。与继发性噬血细胞性淋巴组织细胞增生症（sHLH）患者相比，pHLH 患者更易出现中枢神经系统受累（50% vs. 25.3%，P = 0.001）。8 例 pHLH 患者首发时为孤立性 CNS-HLH，在 10-30 天至数年时间内进展为全身 HLH。其中 5 例接受造血干细胞移植（HSCT）治疗的患者存活，无中枢神经系统后遗症，未行 HSCT 的 3 例患者因疾病进展或复发而死亡。NK 细胞细胞毒性和 CD107a 水平测定在 pHLH 的诊断中敏感性和特异性均较低，尤其是在 PRF1 和 XIAP 突变患者中。与 sHLH 患者（74.5%±14.7% vs. 89.2%±3.53%，P = 0.021）和无中枢神经系统受累患者（53.8%±26.07% vs. 94.4%±10.58%，P = 0.012）相比，pHLH 患者的 3 年总生存率（OS）明显较低。pHLH 患者不同基因变异的 OS 存在显著差异（P = 0.032）；PRF1 变异患者的 3 年 OS 较差，XIAP 变异患者的 3 年 OS 较好（分别为 50%±28.22%和 100%）。具有不同变异的 pHLH 患者具有不同的预后。孤立性 CNS-HLH 患者易误诊，HSCT 可能对这些患者有益。NK 细胞细胞毒性和 CD107a 水平测定不能准确区分 pHLH 与 sHLH。
