伴有染色体1p36缺失的高危神经母细胞瘤自体造血干细胞移植巩固治疗的近期疗效分析

目的总结和分析伴有染色体1p36缺失的高危神经母细胞瘤(HR-NB)的临床特征,分析这些患儿经过自体造血干细胞移植巩固治疗后的近期疗效,为进一步提高HR-NB生存率提供参考依据。方法回顾性分析2014年4月-2016年4月,北京儿童医院血液肿瘤中心收治的HR-NB患儿的临床资料。HR-NB诊断标准、临床分期、治疗方案和疗效标准均根据北京儿童医院HR-NB方案(BCH-HR-NB-2007),入组患儿为同时伴有染色体1 p36缺失,且均经过系统治疗和随访的HR-NB。随访至2016年12月31日。结果入组患儿共11例(男4例,女7例),平均年龄43个月,临床分期均为INSS-Ⅳ。肿瘤原发于后纵隔3例,腹膜后或肾上腺8例。骨髓转移11例,骨骼转移10例,均为多发骨转移,远处淋巴结转移6例,肝脏等内脏转移5例,中枢转移2例。伴有N-myc基因扩增4例。全部患儿术前化疗4~5个疗程,回输干细胞计数为(2.62~10.68)×10~6/kg,中位随访时间14.9(9~32)个月。4例患儿复发或进展,其中1例停维甲酸3个月后骨髓复发,放弃治疗后死亡;另3例分别于干细胞回输后第3、5和6个月,维持治疗中肿瘤进展,2例放弃后死亡,1例仍在治疗中。余7例患儿处于肿瘤稳定状态。结论伴有染色体1 p36缺失的HR-NB患儿,骨髓和骨骼转移率极高,约1/3同时伴有N-myc基因扩增。自体造血干细胞移植巩固治疗后3~6个月内,仍然容易出现肿瘤进展。提示肿瘤恶性程度高,很容易进展或复发,在干细胞移植巩固治疗后维持治疗期间仍需要增加全身治疗的强度。

Clinical effects of high risk neuroblastoma with chromosome 1p36 deletion post autologous hematopoietic stem cell transplantation

Objective By describing the clinical features of post autologous hematopoietic stem cell transplantation high risk Neuroblastoma (HR-NB) patients with 1 p36 deletion and their clinical outcomes,the goal was to make further progress in better survival rate and life quality.Methods A retrospective study of all HR-NB patients with lp36 deletion,who attended the pediatric hematology oncology centre from April 2014 to April 2016 and received systematic treatment and follow-up care,were performed.Clinical stage,risk group classification,treatment and assessment were according to NB-2007-protocol of the centre.The end of follow-up was Dec 31st,2016.Results A total of 11 HR-NB patients with 1 p36 deletion,all INSS-Ⅳ,were included in the study (4 male and 7 female).The average age was 43 months.Primary tumor sites of 3 cases were in the posterior mediastinum,and the test 8 cases were in retroperitoneal or adrenal gland.There were 11 cases with bone marrow metastasis and 10 cases with multiple bone metastasis.There were 6 cases with distant lymph node metastasis,5 cases with visceral metastasis,such as in liver.N-myc gene amplification was detected in 4 patients.All the patients were treated with 4-5 courses of chemotherapy before the operation.The amount of infused stem cells was (2.62-10.68) × 106/kg,and the median follow-up time was 14.9 (9-32) months.4 patients relapsed or progressed,1 of whom relapsed after 3 months of stopping retinoic acid and died after giving up treatment.3 cases occurred tumor progression in 3,5 and 6 months after the infusion respectively.2 patients died after abandonment,and 1 patient was still under treatment.All the 7 patients in have stable disease.Conclusions HR-NB patients with 1 p36 deletion had a high risk of developing bone marrow and bone metastases,and 1/3 of them were associated with N-myc gene amplification.However,in 3-6 months after reinfusion and during retinoic acid maintenance therapy,tumor progression may happen and lead to poor prognosis,suggesting the strength of systemic treatment of these patients is not quite enough.