Objective: To analyze the clinical characteristics of newly treated high-risk group neuroblastoma (NB) patients with bone marrow metastasis and to explore the prognostic factors. Methods: The clinical features (sex, age, stage, risk group, pathological type, metastatic site, etc.) of 203 newly treated high-risk NB patients with bone marrow metastasis admitted to Hematology Oncology Center, Beijing Children's Hospital from January 2007 to December 2016 were analyzed retrospectively. There were 118 males (58.1%) and 85 females (41.9%). Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. Results: The age at onset of the 203 patients was 41 months (9-147 months). The metastatic sites at diagnosis were as follows: bone in 195 cases (96.1%), distant lymph nodes in 104 cases (51.2%), skull and endomeninx in 61 cases (30.0%), orbit in 30 cases (14.8%), pleura in 16 cases (7.9%), liver in 13 cases(6.4%), canalis spinalis in 13 cases (6.4%), other sites in 11 cases (5.4%) and skin and soft tissue in 10 cases (4.9%). In all, 194 cases were enrolled for prognostic analysis. The follow-up time was 36 months (1 day-138 months) , and the 5-years event free survival (EFS) and overall survival (OS) were 36.1% and 39.7%, respectively. A total of 118 patients (60.8%) had events (first relapse or death) with the time to event occurrence was 15 months (1 day-72 months), whereas 112 patients (57.7%) died with the event occurrence to death time was 3 months (1 day-21 months). There was no significant difference in 5-years OS between radiotherapy group and non-radiotherapy group (42.3% vs. 38.3%, χ(2)=3.671, P=0.055). The 5-years OS in transplantation group was significantly better than the non-transplantation group (44.3% vs. 35.5%, χ(2)=8.878, P=0.003), and the radiotherapy combined transplantation group also had a better 5-years OS rate than the non-radiotherapy combined transplantation group (45.8% vs. 37.3%, χ(2)=5.945, P=0.015). Univariate survival analysis showed lactate dehydrogenase ≥ 1 500 U/L, the amplification of MYCN, the metastatic sites of orbit, canalis spinalis and pleura were associated with poor prognosis of newly diagnosed high-risk NB patients (χ(2)=21.064, 13.601, 3.998, 6.183, 15.307, all P<0.05). The amplification of MYCN and the metastatic sites of pleura were risk factors for prognosis of newly diagnosed high-risk NB patients by Cox regression models (HR=1.896,1.100, 95%CI: 1.113-3.231, 1.020-1.187, both P<0.05). Conclusions: The prognosis is unfavorable in high-risk group NB patients with BM metastasis. Radiotherapy combined with transplantation can further improve the prognosis of these patients. The amplification of MYCN and the metastatic sites of pleura were the poor prognostic factors for high-risk NB patients with bone marrow metastasis.
目的： 分析初治伴骨髓转移的高危神经母细胞瘤（NB）患儿的临床特征，探讨其预后影响因素。 方法： 回顾性分析2007年1月至2016年12月北京儿童医院血液肿瘤中心收治的203例初治伴骨髓转移高危NB患儿资料，其中男118例（58.1%），女85例（41.9%）。对患儿临床特征（包括性别、年龄、分期、危险度分组、病理类型、转移瘤灶部位等）进行分析，采用Kaplan-Meier方法进行生存分析，使用Cox模型进行预后因素分析。 结果： 203例患儿发病年龄41（9~147）月龄。转移部位依次为骨骼195例（96.1%），远处淋巴结104例（51.2%），颅骨及脑膜61例（30.0%），眼眶30例（14.8%），胸膜16例（7.9%），肝脏13例（6.4%），椎管内13例（6.4%），其他部位11例（5.4%），皮肤及软组织10例（4.9%）。194例患儿纳入预后分析，随访时间36个月（1 d~138个月），5年无事件生存率（EFS）和总生存率（OS）分别为36.1%和39.7%。118例（60.8%）患儿发生事件（第一次进展或死亡），事件发生时间15个月（1 d~72个月），112例（57.7%）患儿死亡，事件发生至死亡时间3个月（1 d~21个月）。放疗组5年OS与未放疗组差异无统计学意义（42.3%比38.3%，χ(2)=3.671，P=0.055）；移植组5年OS明显优于未移植组（44.3%比35.5%，χ(2)=8.878，P=0.003）；放疗联合移植组5年OS明显优于非放疗联合移植组（45.8%比37.3%，χ(2)=5.945，P=0.015）。单因素分析显示初诊时乳酸脱氢酶≥1 500 U/L、MYCN扩增、眼眶转移、椎管内转移及胸膜转移的患儿预后不良（χ(2)=21.064、13.601、3.998、6.183、15.307，P均<0.05）。Cox多因素分析显示MYCN扩增和胸膜转移为影响伴骨髓转移NB患儿预后的危险因素（HR=1.896、1.100，95%CI：1.113~3.231、1.020~1.187，P均<0.05）。 结论： 伴骨髓转移高危NB患儿预后较差，放疗联合移植可进一步提高该组患儿的预后，诊断时MYCN扩增及胸膜转移是影响伴骨髓转移高危NB患儿预后的不良因素。.
Keywords: Bone marrow; Child; Neuroblastoma; Prognosis.