Objective: To analyze the clinical characteristics and long-term outcome of Langerhans cell histiocytosis with multisystem involvement (MS-LCH) in children, and to evaluate the efficacy of modified DAL-HX83/90 protocol. Methods: This retrospective study included 53 patients with MS-LCH admitted to the Department of Pediatric Hematology and Oncology, First Affiliated Hospital of Zhengzhou University from January 2011 to May 2019. Modified DAL-HX83/90 protocol was used in all patients as an initial treatment. The patients were divided into the group with (RO+) or without (RO-) risk organ involvement. The RO+group was further divided into two groups, as RO+Ⅰ group (lung involvement only) and RO+Ⅱ group (extra-pulmonary, with or without lung involvement). The clinical characteristics and the long-term outcome were summarized. Event-free survival (EFS) and overall survival (OS) curves were analyzed with Kaplan-Meier method. Univariate and multivariate analysis of prognostic factors including age, sex, risk organ involvement and response to 6-week induction were analyzed with Log-Rank test and Cox proportional hazards models. Results: Among the 53 children with MS-LCH, 34 were male and 19 were female. The age of onset was 21 months (3 months-13 years). There 22 were in RO+group, with 12 in RO+Ⅰ group and 10 in RO+Ⅱ group, and 31 in RO-group. The follow-up period was 51 (12-144) months. The overall response rate of 6-week induction was 89% (47/53), and the recurrence rate was 30% (16/53). The 5-year EFS and OS were (67±6) % and (83±5) %, respectively. Univariate analysis showed that the 5-year EFS and OS of patients who responded well to 6-week induction chemotherapy were significantly higher than those who had no response ((76±6) % vs. 0, (88±4) % vs. (41±22) %, χ2 = 34.743, 10.608, both P<0.05). The 5-year EFS and OS of RO-group were significantly higher than that of RO+group ((80±7) % vs. (49±10) %, (93±4) % vs. (70±10) %, χ2=6.022, 4.793, both P<0.05). And the 5-year EFS of RO+Ⅰ group was significantly higher than that of RO+Ⅱ group ((83±10) % vs. (10±9) %, χ2=9.501, P=0.002). While age and sex were not significantly associated with 5-year EFS and OS (all P>0.05). Cox proportional hazard regression model showed that response to 6-week induction chemotherapy was the independent risk factor for EFS (HR=13.114, 95%CI 3.759-45.742, P<0.01) and OS (HR=7.748, 95%CI 1.542-38.920, P=0.013). Conclusions: Most of the children without risk organ involvement treated with modified DAL-HX83/90 protocol could achieve long-term survival. However, the children involved liver, spleen, or hematopoietic system had a high risk of disease progression and recurrence.
目的： 分析多系统受累朗格罕细胞组织细胞增生症（MS-LCH）患儿的临床特征及远期预后，评价改良DAL-HX83/90方案对MS-LCH患儿的疗效。 方法： 回顾性病例分析。研究对象为2011年1月至2019年5月郑州大学第一附属医院儿童医院血液肿瘤科收治的53例MS-LCH患儿，初始化疗采用改良DAL-HX83/90方案，按是否累及危险器官分为无危险器官受累（RO-）组和累及危险器官（RO+）组，RO+组再分为Ⅰ组（仅肺受累）、Ⅱ组（肺外，伴或不伴肺受累），总结临床特征和随访结果，Kaplan-Meier生存分析法计算生存率，Log-Rank检验及Cox比例风险回归模型对年龄、性别、危险器官受累、6周诱导化疗反应进行单因素及多因素预后分析。 结果： 53例MS-LCH患儿中男34例、女19例，发病年龄21月龄（3月龄至13岁），RO-组31例，RO+组22例，其中Ⅰ组12例、Ⅱ组10例。随访时间51（12~144）个月，6周诱导化疗有效率89%（47/53），进展复发率30%（16/53），5年无事件生存率（EFS）为（67±6）%，5年总生存率（OS）为（83±5）%。单因素分析发现6周诱导化疗有效者5年EFS、OS明显高于无效者［（76±6）%比0，（88±4）%比（41±22）%］，差异均有统计学意义（χ²=34.743、10.608，均P<0.05）。RO-组5年EFS、OS明显高于RO+组［（80±7）%比（49±10）%，（93±4）%比（70±10）%］，差异均有统计学意义（χ²=6.022、4.793，均P<0.05）。Ⅰ组5年EFS明显高于Ⅱ组［（83±10）%比（10±9）%］，差异有统计学意义（χ²=9.501，P=0.002），年龄、性别与EFS、OS无明显相关性（均P>0.05）。Cox比例风险回归模型分析发现6周诱导化疗反应是影响EFS（HR=13.114，95%CI 3.759~45.742，P<0.01）、OS（HR=7.748，95%CI 1.542~38.920，P=0.013）的独立危险因素。 结论： 采用改良DAL-HX83/90方案治疗无危险器官受累MS-LCH，患儿多数可获长期生存。但累及肝、脾或造血系统的MS-LCH患儿疾病进展和复发率较高。.
Keywords: Child; Histiocytosis; Langerhans cells; Prognosis.