大剂量化疗造血干细胞移植治疗IV期神经母细胞瘤的长期疗效研究

Long-term effect of high dose chemotherapy combined with stem cell transplantation on stage IV neuroblastoma in children

目的 目前Ⅳ期神经母细胞瘤患儿无论采用何种方法治疗均疗效差，长期生存率低，需要探索新的治疗途径。该文采用大剂量化疗、自体外周血造血干细胞移植及13-顺式维甲酸治疗等方法，试图提高Ⅳ期神经母细胞瘤的长期疗效。方法选择Ⅳ期神经母细胞瘤患儿28例，年龄2．1-11．5岁，平均3．3±1．9岁，发病时间1-7个月，平均3．1±0．7个月。原发部位：肾上腺23例，胸部3例，胸腹联合1例，骶骨1例。强烈化疗6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，术后行局部放疗及13-顺式维甲酸治疗，定期随访。结果28例患儿诱导化疗结束时13例取得完全缓解，11例取得部分缓解，4例化疗中病情进展。完全缓解及部分缓解的24例患儿完成治疗进入本研究。随访3．5±0．7年，两组4年无病生存率29．2％。完全缓解组中位无复发生存时间4．1±0．7年；部分缓解组中位无复发生存时间2．8±0．5年，两组中位无复发生存时间差异有显著性（t=3．9，P〈0．01）。结论大剂量化疗、自体外周血造血干细胞移植及13．顺式维甲酸治疗Ⅳ期神经母细胞瘤可取得较好疗效，4年无病生存率29．2％，移植前达到完全缓解时可取得更好疗效。

Objective Neuroblastoma is a highly malignant tumor. Stage IV neuroblastoma has a very poor long-term outcome by conventional chemotherapy and surgery and better therapies are essential. This study aimed to explore the long-term effect of high dose induction chemotherapy combined with autologous peripheral blood stem cell transplantation and 13-cis retinoid acid treatment on stage IV neuroblastoma in children. Methods Twenty-eight children with stage IV neuroblastoma, aged 2.1-11.5 years （ mean 3.3±1.9 years） , were employed for the study. Primary sites of the tumors included adrenal （ n = 23 ） , chest （ n = 3 ） , chest-abdomen （ n = 1 ） and sacrum （ n = 1 ）. Before autologous peripheral blood stem cell transplantation the patients received 6 courses of intensive induction chemotherapy. During chemotherapy the autologous peripheral blood stem cells were harvested and the tumor excision was done. After transplantation the local radiation and 13-cis retinoid acid therapy were administered. Results After 6 courses of induction chemotherapy 13 patients got complete remission （CR） , 11 got partial remission （PR） , and 4 had no response. The 24 patients who received CR or PR completed the full therapy. A 3.5±0.7 years follow-up showed that the 4-year event-free survival of the CR and PR patients was 29.2%. The median no-relapse survival time in CR patients was 4.1±0.7 years but 2.8± 0.5 years in PR patients （t = 3.9, P 〈 0.01 ）. Conclusions High dose chemotherapy combined with autologous peripheral stem cell transplantation and 13 cis-retinoid acid treatment can improve the long-term outcome of patients with stage IV neuroblastoma. The patients in CR before transplantation had better outcomes than those in PR.