Hematological involvement (HI) is one of the life-threatening risk organs (ROs) in Langerhans cell histiocytosis (LCH). Lahey criteria have defined HI since 1975 as hemoglobin <10 g/dL, platelets <100 G/L, leukopenia (white blood cell count <4 G/L), and/or neutrophils <1.5 G/L. Among the 2313 patients aged <18 years enrolled in the French National Histiocytosis Registry (1983-2023), 331 developed HI (median age at diagnosis, 1 year); median follow-up lasted 8.1 years. Bone marrow aspirate smears and biopsies may show reactive histiocytes, hemophagocytosis, or myelofibrosis but never confirm the diagnosis. Fifty-eight patients (17%) developed macrophage-activation syndrome, sometimes related to acute Epstein-Barr virus or cytomegalovirus infection, sometimes months before typical LCH manifestations appeared. Hemoglobin and platelet thresholds for initiating transfusion(s) appear to accurately distinguish 2 groups: mild HI (MHI; >7 g/dL and >20 G/L, respectively) and severe HI (SHI; ≤7 g/dL and ≤20 G/L). Each entity has different organ involvements, laboratory parameters, mutational status, blood BRAFV600E loads, drug sensitivities, and outcomes (MHI and SHI 10-year survival rates, 98% and 73%, respectively). Since 1998, mortality first declined with combination cladribine-cytarabine therapy and then with MAPK inhibitors since 2014. Forty-one patients (12%) developed neurodegenerative complications that have emerged as a risk for long-term survivors. These results suggest limiting the HI-RO definition to SHI, because it encompasses almost all medical complications of LCH. Future clinical trials might demonstrate that targeted therapy approaches would be better adapted for these patients, whereas MHI can be managed with classic therapies.

中文翻译：

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儿童朗格汉斯细胞组织细胞增多症血液学受累：与BRAFV600E负荷相关的严重程度


血液学受累 （HI） 是朗格汉斯细胞组织细胞增生症 （LCH） 中危及生命的风险器官 （RO） 之一。自 1975 年以来，Lahey 标准将 HI 定义为血红蛋白 <10 g/dL、血小板 <100 G/L、白细胞减少症（白细胞计数 <4 G/L）和/或中性粒细胞 <1.5 G/L。在法国国家组织细胞增多症登记处 （1983-2023） 登记的 2313 名年龄为 <18 岁的患者中，331 名患者发生 HI （诊断时的中位年龄为 1 岁）;中位随访持续 8.1 年。骨髓穿刺涂片和活检可能显示反应性组织细胞、噬血细胞增多或骨髓纤维化，但无法确诊。58 例患者 （17%） 发生巨噬细胞活化综合征，有时与急性 EB 病毒或巨细胞病毒感染有关，有时在典型 LCH 表现出现前数月出现。开始输血的血红蛋白和血小板阈值似乎可以准确区分两组：轻度 HI （MHI;分别为 >7 g/dL 和 >20 G/L）和重度 HI （SHI;≤7 g/dL 和 ≤20 g/L）。每个实体具有不同的器官受累、实验室参数、突变状态、血BRAFV600E载量、药物敏感性和结局 （MHI 和 SHI 10 年生存率分别为 98% 和 73%）。自 1998 年以来，克拉屈滨-阿糖胞苷联合治疗首先降低死亡率，然后自 2014 年以来使用 MAPK 抑制剂降低。41 名患者 （12%） 出现神经退行性并发症，这些并发症已成为长期幸存者的风险。这些结果表明将 HI-RO 定义限制为 SHI，因为它几乎涵盖了 LCH 的所有医学并发症。未来的临床试验可能会表明，靶向治疗方法更适合这些患者，而 MHI 可以通过经典疗法进行管理。