Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, China.
Leukemia. 2024 Apr;38(4):803-809. doi: 10.1038/s41375-024-02174-1. Epub 2024 Feb 22.
Langerhans cell histiocytosis (LCH) lacks a standardized first-line therapy. This single-center, phase 2 prospective study (NCT04121819) enrolled 61 newly diagnosed adult LCH patients with multisystem or multifocal single system disease from October 2019 to June 2022. Subcutaneous cytarabine (100 mg/m2 for 5 days) was administered in 35-day cycles for 12 total cycles. The primary endpoint was event-free survival (EFS). The median age was 33 years (range 18-66). Twelve patients (19.7%) had liver involvement, of which 2 also had spleen involvement. Among 43 patients undergoing next-generation sequencing, BRAF alterations (44.2%) were most frequent, followed by TP53 (16.3%), MAP2K1 (14.0%) and IDH2 (11.6%). MAPK pathway alterations occurred in 28 patients (65.1%). The overall response rate was 93.4%, with 20 (32.7%) achieving complete response and 37 (60.7%) partial response. After a median 30 months follow-up, 21 (34.4%) relapsed without deaths. Estimated 3-year OS and EFS were 100.0% and 58.5%, respectively. Multivariate analysis identified ≥3 involved organs (P = 0.007; HR 3.937, 95% CI: 1.456-9.804) and baseline lung involvement (P = 0.028; HR 2.976, 95% CI: 1.126-7.874) as poor prognostic factors for EFS. The most common grade 3-4 toxicities were neutropenia (27.9%), thrombocytopenia (1.6%), and nausea (1.6%). In conclusion, cytarabine monotherapy is an effective and safe regimen for newly diagnosed adults, while baseline lung or ≥3 involved organs confers poor prognosis.
朗格汉斯细胞组织细胞增生症（LCH）缺乏标准化的一线治疗方法。这项单中心、2 期前瞻性研究（NCT04121819）纳入了 2019 年 10 月至 2022 年 6 月期间 61 例新诊断的成人多系统或多灶性单系统疾病的 LCH 患者。在 35 天的周期中，给予皮下阿糖胞苷（100mg/m2，连用 5 天），总共 12 个周期。主要终点是无事件生存（EFS）。中位年龄为 33 岁（范围 18-66 岁）。12 例（19.7%）有肝脏受累，其中 2 例还伴有脾脏受累。在 43 例接受下一代测序的患者中，BRAF 改变（44.2%）最为常见，其次是 TP53（16.3%）、MAP2K1（14.0%）和 IDH2（11.6%）。MAPK 通路改变发生在 28 例患者（65.1%）中。总缓解率为 93.4%，20 例（32.7%）达到完全缓解，37 例（60.7%）达到部分缓解。中位随访 30 个月后，21 例（34.4%）复发，无死亡病例。估计 3 年 OS 和 EFS 分别为 100.0%和 58.5%。多变量分析确定≥3 个受累器官（P=0.007；HR 3.937，95%CI：1.456-9.804）和基线肺部受累（P=0.028；HR 2.976，95%CI：1.126-7.874）是 EFS 的不良预后因素。最常见的 3-4 级毒性是中性粒细胞减少（27.9%）、血小板减少（1.6%）和恶心（1.6%）。总之，阿糖胞苷单药治疗是新诊断成人的一种有效且安全的治疗方案，而基线肺部受累或≥3 个受累器官预示预后不良。
