儿童颅面骨受累的朗格罕细胞组织细胞增生症临床分析

Clinical analysis of pediatric Langerhans cell histiocytosis with craniofacial bone involvement

目的了解儿童颅面骨受累的朗格罕细胞组织细胞增生症(LCH)的临床特点及预后。方法回顾性分析2007年1月至2013年7月首都医科大学附属北京儿童医院血液肿瘤中心收治的145例颅面骨受累的LCH患儿的临床资料。将颅面骨受累的LCH患儿分为中枢神经系统风险(CNS-RISK)颅面骨受累组和非CNS-RISK颅骨受累组。患儿于化疗5周、11周、25周、52周及停药3个月、6个月、1年、3年进行疾病状态评估,分析尿崩症、疾病复发的危险因素。结果145例颅面部受累的LCH患儿占同期232例LCH患儿的62.5%。中位年龄29个月,中位随访31个月。顶骨受累最常见(78例,53.8%),其次为颞骨(59例,40.7%)、额骨(57例,39.3%)。CNS-RISK颅面骨受累组患儿103例,非CNS-RISK颅骨受累组患儿42例,前者中位发病年龄(26个月)显著低于后者(54个月),前者多系统危险器官受累患儿(72/103例,69.9%)比例显著多于后者(15/42例,35.7%),差异均有统计学意义(Z=-2.777,χ^2=16.908,均P<0.05)。患儿总体复发率为35.9%(52/145例),CNS-RISK颅面骨受累组(45/103例,43.7%)明显高于非CNS-RISK颅面骨受累组(7/42例,16.7%),且前者3年无复发生存率明显低于后者[(66.9±5.7)%比(88.2±7.8)%],差异均有统计学意义(χ^2=9.427,Z=2.205,均P<0.05)。同期232例LCH患儿,尿崩症发生率13.7%,颅面骨受累患儿尿崩症发生率(27/145例,18.6%)明显高于非颅面骨受累患儿(5/87例,5.7%),差异有统计学意义(χ^2=7.579,P=0.006);CNS-RISK颅面骨受累组与非CNS-RISK颅面骨受累组尿崩症发生率比较差异无统计学意义(21.3%比11.9%,χ^2=1.760,P=0.185)。单系统CNS-RISK颅面骨受累患儿未出现尿崩症。至随诊截止时间,仅1例患儿死亡。3.4%(5/145例)单发的CNS-RISK颅面骨受累患儿均接受系统化疗,无尿崩症及死亡病例,1例复发。多因素分析提示,累及顶骨、额骨、上下颌骨是尿崩症发生的独立风险因素(HR=2.697、3.487、5.425,均P<0.05),累及颞骨、上下颌骨是复发的独立风险因素(HR=3.712、3.380,均P<0.05)。结论顶骨是LCH患儿最常见受累的颅面骨,CNS-RISK颅面骨受累的LCH患儿发病年龄低、并多系统危险器官比例高、复发率高、3年无复发生存率低。单系统CNS-RISK颅面骨受累患儿尿崩症发生率低。顶骨、额骨、上下颌骨受累的患儿易发生尿崩症,颞骨、上下颌骨受累的患儿易复发。

Objective To investigate the clinical characteristics and outcomes of pediatric Langerhans cell histiocytosis (LCH) with craniofacial bone involvement. Methods A retrospective analysis was performed on 145 pediatric LCH patients with craniofacial bone involvement registered at Beijing Children′s Hospital Affiliated to Capital Medical University from January 2007 to July 2013.The patients were divided into 2 groups: central nervous system risk craniofacial bone involvement group(CNS-RISK) and non-central nervous system risk craniofacial bone involvement group(non-CNS-RISK). All patients were assessed at 5 weeks, 11 weeks, 25 weeks and 52 weeks respectively after chemotherapy started, and 3 months, 6 months, 1 year and 3 years after chemotherapy withdrawal.Statistics and related risk analysis was performed respectively. Results A total of 145 craniofacial bone involved LCH cases were included, which was composed of 62.5% of 232 LCH cases hospitalized during the same period.The median age of these patients was 29 months, and median follow-up time period was 31 months.The most commonly involved craniofacial bone was parietal bone(78 cases, 53.8%), followed by temporal bone(59 cases, 40.7%) and frontal bone(57 cases, 39.3%). The onset age was significantly different (26 months vs.54 months, Z=-2.777, P<0.05) between CNS-RISK group (103 cases) and non-CNS-RISK group (42 cases). Moreover, compared with non-CNS-RISK group, CNS-RISK group showed higher ratio of patients classified as multisystem involvement of risk organs (72/103 cases, 69.9%)vs.(15/42 cases, 35.7%)(χ^2=16.908, P<0.05), and a higher rate of overall relapse rate (45/103 cases, 43.7%) vs.(7/42 cases, 16.7%)(χ2=9.427, P<0.05), a lower survival rate of 3-year relapse-free survival rate [(66.9±5.7)% vs.(88.2±7.8)%, Z=2.205, P<0.05]. The incidence of diabetes insipidus was 13.7% in 232 LCH patients.Compared with patients without craniofacial bone involvement, patients with craniofacial bone involvement demonstrated a higher rate of diabetes insipidus [(27/145 cases, 18.6%) vs.(5/87 cases, 5.7%),χ^2=7.579, P=0.006]. But the incidence of diabetes insipidus showed no statistical difference between CNS-RISK group and non-CNS-RISK group (21.3% and 11.9%,χ^2=1.760, P=0.185). Diabetes insipidus was not found in single system LCH with Single-Bone CNS-RISK lesions.Till the end of follow-up, 1 out of 145 patients died.Among 145 patients, 5 cases had a single-bone CNS-RISK lesion.They received systemic chemotherapy.One showed reactivation, and none of them died.Multivariate analysis of variance showed that all the independent factors indicating diabetes insipidus included parietal bone, frontal bone, maxilla and mandible involvement(HR=2.697, 3.487, 5.425, all P<0.05), while independent factors indicating relapse included temporal bone, maxilla and mandible involvement(HR=3.712, 3.380, all P<0.05). Conclusions Among involved craniofacial bones, the parietal bone is most commonly involved.LCH occurs averagely at an earlier age in CNS-RISK group, along with lower 3-year relapse-free survival rate, high relapse rate, and more patients classified as multisystem LCH involvement of risk organs.The incidence of diabetes insipidus in children with craniofacial bone involvement with single system CNS-RISK is low.Patients with the parietal bone, frontal bone, maxilla and mandible involvement at diagnosis are at a increasing risk a significantly to develop DI during the course of disease.