Thalhammer Julian, Jeziorski Eric, Marec-Bérard Perrine, Barkaoui Mohamed Aziz, Pagnier Anne, Rohrlich Pierre-Simon, Chevallier Aurore, Carausu Liana, Aladjidi Nathalie, Rigaud Charlotte, Leruste Amaury, Azarnoush Saba, Lauvray Thomas, Le Louet Solenne, Gandemer Virginie, Treguier Pauline, Mansuy Ludovic, Pasquet Marlene, Olivier Laura, Rome Angélique, Saultier Paul, Isfan Fiorentina, Renard Cécile, Li Thiao Te Valerie, Salmon Alexandra, Blanc Laurence, Abou Chahla Wadih, Lambilliotte Anne, Stephan Jean-Louis, Geissmann Frederic, Lejeune Julien, Mallebranche Coralie, Reguerre Yves, Grain Audrey, Thomas Caroline, Hélias-Rodzewicz Zofia, Moshous Despina, Fenneteau Odile, Coulomb-L'Hermine Aurore, Lapillonne Hélène, de Saint-Basile Geneviève, Emile Jean-François, Héritier Sébastien, Donadieu Jean
Institute of Hematology and Pediatric Oncology, Centre Leon-Berard, Lyon, France.
Department of Pediatric Hematology, Centre Hospitalo-Universitaire (CHU) de Lille, Lille, France.
Blood. 2025 Mar 6;145(10):1061-1073. doi: 10.1182/blood.2024025625.
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 × 109/L, leukopenia (white blood cell count <4 × 109/L), and/or neutrophils <1.5 × 109/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 × 109/L, respectively) and severe HI (SHI; ≤7 g/dL and/or ≤20 × 109/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.
血液系统受累（HI）是朗格汉斯细胞组织细胞增多症（LCH）中危及生命的风险器官之一。自1975年以来，Lahey标准将HI定义为血红蛋白<10 g/dL、血小板<100×10⁹/L、白细胞减少（白细胞计数<4×10⁹/L）和/或中性粒细胞<1.5×10⁹/L。在法国国家组织细胞增多症登记处登记的2313例18岁以下患者中（1983 - 2023年），331例发生了HI（诊断时的中位年龄为1岁）；中位随访时间为8.1年。骨髓穿刺涂片和活检可能显示反应性组织细胞、噬血细胞现象或骨髓纤维化，但从未确诊。58例患者（17%）发生了巨噬细胞活化综合征，有时与急性爱泼斯坦-巴尔病毒或巨细胞病毒感染有关，有时在典型LCH表现出现前数月发生。启动输血的血红蛋白和血小板阈值似乎能准确区分两组：轻度HI（MHI；分别>7 g/dL和>20×10⁹/L）和重度HI（SHI；≤7 g/dL和/或≤20×10⁹/L）。每个实体具有不同的器官受累情况、实验室参数、突变状态、血液BRAFV600E负荷、药物敏感性和结局（MHI和SHI的10年生存率分别为98%和73%）。自1998年以来，死亡率首先随着克拉屈滨 - 阿糖胞苷联合治疗下降，然后自2014年以来随着丝裂原活化蛋白激酶（MAPK）抑制剂下降。41例患者（12%）发生了神经退行性并发症，已成为长期幸存者的一个风险。这些结果表明将HI - 风险器官的定义限制为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证明靶向治疗方法对这些患者更适用，而MHI可以用经典疗法治疗。
