成人朗格汉斯细胞组织细胞增多症 (LCH) 的最佳治疗策略仍不清楚。我们之前的研究表明，甲氨蝶呤和阿糖胞苷 (Ara-C) [MA] 联合治疗对新诊断为 LCH 的患者具有显着疗效，中位随访时间为 2 年。本文报告了 2014 年 1 月至 2020 年 12 月期间进行的单臂、单中心、前瞻性 2 期临床试验 (NCT02389400) 的中位 78 个月（6.5 年）的长期随访数据。 95患有多系统疾病或多灶性单系统受累的新诊断 LCH 的成人每 35 天接受一次 MA 治疗，持续六个周期。第一天通过24小时输注给予甲氨蝶呤(1g/m2)，并通过24小时输注给予AraC(0.1g/m2)，持续5天。主要终点是无事件生存期（EFS）。患者中位年龄为 32 岁（范围 18-65 岁）。总体答复率为89.5%。该队列中有 7 名患者死亡，38 名患者出现疾病复发。没有观察到退行性中枢神经系统疾病。估计的 6 年总生存率 (OS) 和 EFS 率分别为 93.2% 和 55.2%。多变量分析显示，基线时风险器官 (RO) 受累（风险比 [HR] 6.135 [95% 置信区间 (CI) 1.185-32.259]；p = 0.031），诊断时年龄 >40 岁（HR 7.299 [95% CI]） 1.056-21.277]；p = 0.042）与较差的 OS 相关。基线时 RO（HR 2.604 [95% CI 1.418-4.762]；p = 0.002）和皮肤（HR 2.232 [95% CI 1.171-4.255]；p = 0.015）受累是 EFS 的不良预后因素。关于不良事件，四名患者出现了第二原发恶性肿瘤。总之，MA 方案对于新诊断为 LCH 的成年患者来说是一种有效且安全的治疗方法。© 2024 英国血液学会和 John Wiley

The optimal treatment strategy for adult Langerhans cell histiocytosis (LCH) remains unclear. Our previous study demonstrated the remarkable efficacy of combined methotrexate and cytarabine (Ara-C) [MA] therapy in patients newly diagnosed with LCH, with a median follow-up of 2 years. The present article reports long-term follow-up data spanning a median of 78 months (6.5 years) from a single-arm, single-centre, prospective phase 2 clinical trial (NCT02389400) conducted between January 2014 and December 2020. Ninety-five adults with newly diagnosed LCH exhibiting multisystem disease or multifocal single-system involvement underwent MA therapy every 35 days for six cycles. Methotrexate (1 g/m2) was administered by 24 h infusion on day 1 and AraC (0.1 g/m2) by 24 h infusion for 5 days. The primary end-point was event-free survival (EFS). The median patient age was 32 years (range 18-65 years). The overall response rate was 89.5%. Seven patients in this cohort died, and 38 experienced disease reactivation. No degenerative central nervous system diseases were observed. The estimated 6-year overall survival (OS) and EFS rates were 93.2% and 55.2% respectively. Multivariate analysis revealed that risk organ (RO) involvement at baseline (hazard ratio [HR] 6.135 [95% confidence interval (CI) 1.185-32.259]; p = 0.031) and age >40 years at diagnosis (HR 7.299 [95% CI 1.056-21.277]; p = 0.042) were associated with inferior OS. RO (HR 2.604 [95% CI 1.418-4.762]; p = 0.002) and skin (HR 2.232 [95% CI 1.171-4.255]; p = 0.015) involvement at baseline were poor prognostic factors for EFS. Regarding adverse events, four patients developed a second primary malignancy. In conclusion, the MA regimen was a valid and safe therapeutic approach for adult patients newly diagnosed with LCH.© 2024 British Society for Haematology and John Wiley & Sons Ltd.