儿童神经母细胞瘤早期死亡病例的原因分析

Analysis of early death in children with neuroblastoma

目的总结儿童神经母细胞瘤(NB)诊断初期严重的急危重症及早期死亡原因。分析可能引起NB患儿早期死亡的相关危险因素,以期提高认识,尽早识别和干预,减少早期死亡率。方法连续纳入2007年4月至2017年12月在北京儿童医院血液肿瘤中心初治的NB患儿,并对其中于诊断1个月内死亡的患儿进行回顾性分析。收集患儿的一般资料、直接死亡原因、并发症、死亡发生距诊断相隔时间及是否接受化疗。结果共纳入系统诊治并随访的NB患儿654例,其中31例早期死亡,占同期收治总人数的4.7%。早期死亡患儿主要并发症为肺部感染(18例,58.1%),化疗后骨髓抑制(17例,54.8%),肿瘤破裂出血(16例,51.6%),多脏器功能衰竭(8例,25.8%)。单因素分析:危险度分组(P=0.0066)、骨髓是否侵犯(P=0.0207)、原发肿瘤部位(P=0.0167)、年龄(P=0.0033)、乳酸脱氢酶(LDH)(P<0.0001)、神经元特异性烯醇化酶(NSE)(P<0.0001)、血清铁蛋白(P=0.0160)、D-二聚体(P<0.0001)、纤维蛋白原(P=0.0027)、肿瘤直径(P<0.0001)、血红蛋白(P<0.0001)、血小板(P<0.0001)、血清白蛋白(P<0.0001)在早期死亡患儿与非早期死亡患儿间差异有统计学意义。多因素分析:年龄<30个月,OR=2.824(95%CI:1.084~7.359),LDH>1004 IU/L,OR=6.991(95%CI:2.135~22.887),白蛋白<36 g/L,OR=65.237(95%CI:2.024~13.545),血红蛋白<92 g/L,OR=5.358(95%CI:2.024~13.545),血小板低于192×109/L,OR=3.554(95%CI:1.267~9.965)。结论患儿入院后加强生命体征检测,尽早识别肿瘤破裂等危及生命的急重症,并于有创操作后尽早适当镇静、积极输注血制品等对症干预治疗措施,必要时转重症监护室予呼吸支持等是避免早期死亡的重要手段。

Objective To summarize the causes of death and severe complication in the early diagnosis of children with neuroblastoma(NB),and to analyze the relative factors of early death of children with NB,so as to raise awareness and reduce early mortality by early detection and early intervention.Methods Patients with newly diagnosed NB in the Hematology Oncology Center of Beijing Children′s Hospital from April 2007 to December 2017 were included consecutively,and those died within 1 month after diagnosis were retrospectively analyzed.The general data of patients,immediate causes of death,complications,time elapsed between death and diagnosis,whether to receive chemotherapy and other information were collected.Results A total of 654 cases were included for diagnosis,treatment and follow-up,31 cases of which died in early stage,accounting for 4.7%of the total.The major complication were pulmonary infection in 18 cases(58.1%)and bone marrow suppression after chemotherapy in 17 cases(54.8%),tumor rupture hemorrhage in 16 cases(51.6%),multiple organ failure in 8 cases(25.8%).Risk factor analysis of the 31 early death cases with NB was conducted.Single factor analysis:there were statistical differences between early death group and non-early death group in risk grouping(P=0.0066),bone marrow invasion(P=0.0207),site of primary tumor(P=0.0167),age(P=0.0033),lactate dehydrogenase(LDH)level(P<0.0001),neuron-specific enolase(NSE)level(P<0.0001),serum ferritin level(P=0.0160),D dimer level(P<0.0001),fibrinogen level(P=0.0027),diameter of tumor(P<0.0001),hemoglobin(P<0.0001),platelet level(P<0.0001),serum albumin level(P<0.0001).Multiple-factor analysis:age younger than 30 months,OR=2.824(95%CI:1.084-7.359),LDH level greater than 1004 IU/L,OR=6.991(95%CI:2.135-22.887),albumin level less than 36 g/L,OR=65.237(95%CI:2.024-13.545),hemoglobin level less than 92 g/L,OR=5.358(95%CI:2.024-13.545),platelet level less than 192×109/L,OR=3.554(95%CI:1.267-9.965).Conclusions Strengthening vital signs detection after admission,identifying severe life-threatening complications such as rupture of tumors as early as possible,implementing symptomatic interventions such as appropriate sedation and active transfusion of blood products as early as possible after invasive operation,and transferring to intensive care unit for respiratory support when necessary are important means to avoid early death.