儿童多系统受累朗格罕细胞组织细胞增生症53例临床分析

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。

Clinical manifestations of Langerhans cell histiocytosis with multisystem involvement in 53 children

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+Ⅰgroup(lung involvement only)and RO+Ⅱgroup(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+Ⅰgroup and 10 in RO+Ⅱgroup,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+Ⅰgroup was significantly higher than that of RO+Ⅱgroup((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.