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目的:目前采用常规化疗对Ⅳ期神经母细胞瘤患儿治疗效果欠佳,长期生存率低,本文对采用大剂量化疗结合自体外周血造血干细胞移植及免疫治疗的18例Ⅳ期神经母细胞瘤患儿疗效进行探讨。方法:选择2005年10月～2008年8月收治的Ⅳ期神经母细胞瘤患儿18例,移植时完全缓解(CR)8例,部分缓解(PR)6例,处于肿瘤进展期4例。年龄1.41～14.33岁,平均6.46±3.25岁,中位年龄6.415岁。原发部位:后腹膜5例,肾上腺9例,胸部3例,胸腹联合1例。强烈化疗4～18个疗程,平均9±3.96个疗程,期间进行外周血造血干细胞采集、手术切除,然后进行自体外周血造血干细胞移植,术后行白介素-2及维甲酸生物治疗,复发者行普通化疗及局部放疗,定期随访。结果:18例患儿自体外周血造血干细胞移植治疗结束后,1例进展期患儿于移植后5天因心肺功能衰竭死亡,17例顺利度过移植后骨髓抑制期,造血重建时间为15～19天,平均16.53±0.91天。术后随访3～34.9个月,平均15.89±10.37个月,中位随访时间为13.8个月,完全缓解期8例获得完全缓解,2例术后1年原发灶复发再行普通化疗及局部放疗仍敏感,带瘤生存;部分缓解期3例获得完全缓解,3例获得部分缓解,移植后8个月2例部分缓解期患儿因颅内转移死亡,1例部分缓解期患儿带瘤生存;进展期3例移植重建后稍缓解,分别于移植后3、4、6个月复发、重要脏器转移死亡。完全缓解期13.8个月无病生存率75%;部分缓解期13.8个月,无病生存率50%;进展期13.8个月,生存率为0。3组自体干细胞移植术后13.8个月,无病生存率有差别(P<0.05)。3组13.8个月总无病生存率50%,生存率66.7%。结论:大剂量化疗、自体外周血造血干细胞移植及白介素-2、维甲酸生物治疗相结合治疗Ⅳ期神经母细胞瘤,在移植前达到完全缓解时可取得较好疗效,部分缓解期进行自体干细胞移植可提高缓解率,进展期患儿复发率高,远期治疗效果差。
OBJECTIVE: At present, the treatment effect of conventional chemotherapy on children with neuroblastoma of stage Ⅳ is poor and the long-term survival rate is low. In this paper, 18 cases of stage Ⅳ neuroblastoma with high-dose chemotherapy combined with autologous peripheral blood stem cell transplantation and immunotherapy Children efficacy to explore. Methods: 18 children with stage Ⅳ neuroblastoma who were admitted to our hospital from October 2005 to August 2008 were enrolled. Among them, 8 were completely relieved (CR) at transplantation, 6 were partially relieved (PR) and 4 were at advanced stage. Ages 1.41 to 14.33 years, mean 6.46 ± 3.25 years old, the median age of 6.415 years old. Primary site: 5 cases of retroperitoneal, 9 cases of adrenal, 3 cases of thoracic and thoracoabdominal in 1 case. Intensive chemotherapy 4 to 18 courses, an average of 9 ± 3.96 courses during which hematopoietic stem cell collection, surgical resection, and then autologous peripheral blood stem cell transplantation, postoperative interleukin-2 and retinoic acid biotherapy, recurrent line General chemotherapy and local radiotherapy, regular follow-up. Results: After 18 cases of autologous peripheral blood stem cell transplantation were completed, 1 case of advanced child died of cardiorespiratory failure 5 days after transplantation, 17 cases successfully passed bone marrow suppression after transplantation, and the time for hematopoietic reconstitution was 15 ~ 19 days, an average of 16.53 ± 0.91 days. The patients were followed up for 3 to 34.9 months, with an average of 15.89 ± 10.37 months. The median follow-up time was 13.8 months. Complete remission was achieved in 8 of the 8 cases. Complete remission was achieved in 2 cases of recurrent primary tumor at 1 year after surgery. Radiotherapy was still sensitive, with tumor survival; partial remission in 3 patients achieved complete remission, 3 patients were partially relieved, 8 months after transplantation in 2 patients with partial remission of death due to intracranial metastases, 1 patients with partial remission of tumor Survival; 3 cases of advanced reconstruction after transplantation slightly relieved, respectively, 3,4,6 months after transplantation recurrence, transfer of vital organs and death. The complete remission of 13.8 months disease-free survival rate of 75%; part of the remission of 13.8 months, disease-free survival rate of 50%; progress of 13.8 months, the survival rate was 0.3 group of autologous stem cell transplantation 13.8 months, no Disease survival rates were different (P <0.05). The total disease-free survival rate was 50% in 13.8 months and 66.7% in 3 groups. Conclusion: High-dose chemotherapy, autologous peripheral blood stem cell transplantation and interleukin-2, retinoic acid combined with biotherapy of stage IV neuroblastoma, achieved complete remission before transplantation can achieve good effect, part of the remission of autologous stem cells Transplantation can improve remission rate, high recurrence rate in children with advanced, poor long-term treatment.