Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China.
Ann Med. 2021 Dec;53(1):1537-1546. doi: 10.1080/07853890.2021.1966085.
This study aimed to understand the clinical characteristics and outcomes of children with Langerhans cell histiocytosis (LCH) in China.
We conducted a retrospective study of 95 paediatric patients with LCH in West China Second University Hospital of Sichuan University between July 2013 and August 2020.
The onset age of multisystem LCH (MS-LCH) patients with risk organ (RO) involvement was younger than that of MS-LCH without RO involvement ( = .002) and single system LCH ( < .001) patients; bone was the most frequently involved organ, followed by the skin. Of all, the mutation was detected in 48 out of 84 patients who underwent gene analysis. Additionally, in our study, , , , and were known mutations in the mitogen-activated protein kinase () pathway. The genotype in the tissue and plasma prior to therapy were detected in 16 patients, and the concordance was only 37.5% (6/16). According to the modified LCH-III-based-protocol, JLSG-02 protocol chemotherapy, and vemurafenib, the estimated five-year overall survival, event-free survival (EFS) and cumulative reactivation rates of 95 patients were 98.8%, 74.6% and 24.5%, respectively. The EFS rate in good responders was better than that in poor responders at 12-week (HR = 0.022, 95%CI 0.002-0.231, = .002), and EFS was not affected by age, RO involvement or mutation. Regarding sequelae, nine patients had central diabetes insipidus and two had growth retardation.
In this study, LCH was a highly heterogeneous disease characterized molecularly by MAPK-pathway activating mutations. Vincristine, prednisone and cytarabine-based chemotherapy combined with vemurafenib improved the prognosis of childhood LCH. In future, prospective clinical trials and novel therapeutic strategies should be developed to improve outcomes in paediatric patients with LCH.KEY MESSAGEChildren with Langerhans cell histiocytosis in China present highly heterogeneous clinical characteristics, with up to 60% of cases harbouring mutations in pathway.Treatment response at 12-week is associated with EFS in our study.Vincristine, prednisone and cytarabine-based chemotherapy combined with vemurafenib improved the prognosis of Chinese childhood LCH, but the reactivation rate is still high.
本研究旨在了解中国朗格汉斯细胞组织细胞增生症（LCH）患儿的临床特征和结局。
我们对 2013 年 7 月至 2020 年 8 月在四川大学华西第二医院就诊的 95 例儿童 LCH 患者进行了回顾性研究。
伴有风险器官（RO）受累的多系统 LCH（MS-LCH）患者的发病年龄小于无 RO 受累的 MS-LCH（ = .002）和单系统 LCH（ < .001）患者；骨骼是最常受累的器官，其次是皮肤。在接受基因分析的 84 例患者中，检测到 48 例存在 突变。此外，在本研究中，已知在丝裂原活化蛋白激酶（MAPK）通路中存在 、 、 、 、 突变。16 例患者在治疗前检测了组织和血浆中的 基因型，其一致性仅为 37.5%（6/16）。根据改良的基于 LCH-III 方案、JLSG-02 方案化疗和 vemurafenib，95 例患者的 5 年总生存率、无事件生存率（EFS）和累积再激活率分别为 98.8%、74.6%和 24.5%。12 周时，良好反应者的 EFS 率优于不良反应者（HR=0.022，95%CI 0.002-0.231， = .002），EFS 不受年龄、RO 受累或 突变的影响。关于后遗症，9 例患者出现中枢性尿崩症，2 例患者出现生长迟缓。
在本研究中，LCH 是一种具有高度异质性的疾病，分子特征为 MAPK 通路激活突变。依托泊苷、泼尼松和阿糖胞苷为基础的化疗联合 vemurafenib 改善了儿童 LCH 的预后。未来应开展前瞻性临床试验和新的治疗策略，以改善儿童 LCH 患者的预后。
中国朗格汉斯细胞组织细胞增生症患儿临床表现高度异质，多达 60%的病例存在 通路突变。本研究中，治疗 12 周时的反应与 EFS 相关。依托泊苷、泼尼松和阿糖胞苷为基础的化疗联合 vemurafenib 改善了中国儿童 LCH 的预后，但再激活率仍较高。
