Su Y, Ma X L, Wang H M, Qin H, Qin M Q, Zhang F Q, Jin M, Zhang D W, Chen C H, Zeng Q, He L J, Ni X
Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Beijing 100045, China.
Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Zhonghua Er Ke Za Zhi. 2020 Oct 2;58(10):796-801. doi: 10.3760/cma.j.cn112140-20200525-00540.
To summarize the clinical characteristics of high-risk neuroblastoma (HR-NB) in a single center, analyze the prognostic factors of HR-NB. The clinical data of children with HR-NB who were treated and followed up at the hematology-oncology center of Beijing Children's Hospital from February 1, 2007 to June 30, 2018 were analyzed retrospectively. The clinical features were summarized. Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. The last follow-up time was June 30, 2019. A total of 458 children with HR-NB were enrolled in this study, including 265 males (57.9%) and 193 females (42.1%), the age at diagnosis was 40.0 months (4.5-148.0 months), the follow-up time was 22.0 months (0.2-138.0 months) and the time of tumor progression or recurrence was 15 months (1-72 months). The 5-year event-free survival (EFS) rate was (31.2±2.6)% and the 5-year overall survival (OS) rate was (43.9±3.2)%. The 5-year EFS rate and 5-year OS rate in 142 hematopoietic stem cell transplantation (HSCT) patients with bone marrow metastases were better than that in 196 non-transplantation cases with bone marrow metastases ((26.5±4.5)% . (25.1±3.6)%, χ²=13.773, 0.001; (38.1±5.5)% . (35.7±4.7)%, χ²=9.235, 0.002); 128 transplantation patients with bone metastases had higher 5-year EFS rate and 5-year OS rate than 188 non-transplantation cases with bone metastases ((28.5±5.0)% . (26.7±3.8)%, χ²=10.222, 0.001; (37.1±6.0)% . (36.2±4.8)%, χ²=7.843, 0.005). The 5-year EFS rate was higher in 37 HSCT patients with MYCN amplification than in 49 non-transplantation cases with MYCN amplification ((26.8±8.0) % . (20.5±6.4) %, χ²=5.732, 0.017). No significant difference was found in 5-years OS rate between transplantation group with MYCN amplification and non-transplantation group with MYCN amplification ((31.4±8.6) % . (26.2±7.4) %, χ²=3.230, 0.072). Univariate survival analysis showed that lactate dehydrogenase (LDH)≥1 500 U/L was associated with poor prognosis of patients with MYCN amplification (χ²=6.960, 0.008). Multivariate Cox analysis showed bone marrow metastasis and LDH≥1 500 U/L were independent risk factors for poor prognosis of patients with non-MYCN amplification (=2.427, 1.618;95：1.427-4.126, 1.275-2.054, 0.05) for both comparisons. LDH≥1 500 U/L was the poor prognostic factor for patients with MYCN amplification. The bone marrow metastasis and LDH≥1 500 U/L were the poor prognostic factors for HR-NB patients with non-MYCN amplification. HSCT can improve the prognosis of patients with bone or bone marrow metastasis. It can also retard the time of progression or recurrence for patients with MYCN amplification.
总结单中心高危神经母细胞瘤（HR-NB）的临床特征，分析HR-NB的预后因素。回顾性分析2007年2月1日至2018年6月30日在北京儿童医院血液肿瘤科接受治疗及随访的HR-NB患儿的临床资料。总结临床特征。采用Kaplan-Meier法进行生存分析，Cox回归分析预后因素。末次随访时间为2019年6月30日。本研究共纳入458例HR-NB患儿，其中男性265例（57.9%），女性193例（42.1%），诊断时年龄为40.0个月（4.5 - 148.0个月），随访时间为22.0个月（0.2 - 138.0个月），肿瘤进展或复发时间为15个月（1 - 72个月）。5年无事件生存率（EFS）为（31.2±2.6）%，5年总生存率（OS）为（43.9±3.2）%。142例发生骨髓转移的造血干细胞移植（HSCT）患者的5年EFS率和5年OS率优于196例未移植的骨髓转移患者（（26.5±4.5）% 对（25.1±3.6）%，χ² = 13.773，P = 0.001；（38.1±5.5）% 对（35.7±4.7）%，χ² = 9.235，P = 0.002）；128例发生骨转移的移植患者的5年EFS率和5年OS率高于188例未移植的骨转移患者（（28.5±5.0）% 对（26.7±3.8）%，χ² = 10.222，P = 0.001；（37.1±6.0）% 对（36.2±4.8）%，χ² = 7.843，P = 0.005）。37例MYCN扩增的HSCT患者的5年EFS率高于49例未移植的MYCN扩增患者（（26.8±8.0）% 对（20.5±6.4）%，χ² = 5.732，P = 0.017）。MYCN扩增的移植组与未移植组的5年OS率差异无统计学意义（（31.4±8.6）% 对（26.2±7.4）%，χ² = 3.230，P = 0.072）。单因素生存分析显示，乳酸脱氢酶（LDH）≥1500 U/L与MYCN扩增患者的预后不良相关（χ² = 6.960，P = 0.008）。多因素Cox分析显示，骨髓转移和LDH≥1500 U/L是未发生MYCN扩增患者预后不良的独立危险因素（两组比较，HR = 2.427，1.618；95%CI：1.427 - 4.126，1.275 - 2.054，P = 0.05）。LDH≥1500 U/L是MYCN扩增患者的不良预后因素。骨髓转移和LDH≥1500 U/L是未发生MYCN扩增的HR-NB患者的不良预后因素。HSCT可改善发生骨或骨髓转移患者的预后，也可延缓MYCN扩增患者的进展或复发时间。
