Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Pediatr Blood Cancer. 2010 Jul 15;55(1):55-9. doi: 10.1002/pbc.22504.
We previously reported promising pilot results treating patients with stage 4a metastatic retinoblastoma with combined intensive conventional chemotherapy, high-dose chemotherapy with autologous hematopoietic stem cell rescue, and radiation therapy and now present an expanded and updated series.
Fifteen patients with bone marrow (n = 14), bone (n = 10), orbit (n = 9), and/or liver (n = 4) disease were treated. Induction chemotherapy usually consisted of vincristine, cyclophosphamide, cisplatin, and etoposide. The high-dose chemotherapy regimen included carboplatin and thiotepa alone (n = 1) or with etoposide (n = 5) or topotecan (n = 7).
Bone marrow cleared at first post-initiation of chemotherapy examination in all patients and stem cells were harvested after a median of 3.5 cycles of chemotherapy (range 3-6 cycles). Two patients progressed prior to high-dose chemotherapy and died. Thirteen received high-dose chemotherapy at a median of 6 months post-diagnosis of metastases (range 4-8 months). Ten are retinoblastoma-free in first remission at a median follow-up of 103 months (range 34-202 months) while three recurred (two in the CNS, one in the mandible) 14-20 months post-diagnosis of metastases. Retinoblastoma-free and event-free survival at 5 years are 67% (95% confidence interval 38-85%) and 59% (95% confidence interval 31-79%). Six of the 10 survivors received radiation therapy. Three patients developed secondary osteosarcoma 14, 4, and 9 years after diagnosis of metastatic disease.
Intensive multimodality therapy including high-dose chemotherapy with autologous hematopoietic stem cell rescue was curative for the majority of patients with stage 4a metastatic retinoblastoma treated. The contribution of external beam radiation therapy is unclear.
我们之前报道了对 4a 期转移性视网膜母细胞瘤患者采用联合强化常规化疗、大剂量化疗联合自体造血干细胞挽救和放疗的有希望的初步结果，现报道扩大和更新的系列结果。
15 例患者有骨髓（n=14）、骨（n=10）、眼眶（n=9）和/或肝脏（n=4）疾病。诱导化疗通常包括长春新碱、环磷酰胺、顺铂和依托泊苷。大剂量化疗方案包括单独使用卡铂和噻替哌（n=1）或联合依托泊苷（n=5）或拓扑替康（n=7）。
所有患者在开始化疗检查后的第一次骨髓均清除，在中位数 3.5 个周期的化疗后采集干细胞（范围 3-6 个周期）。两名患者在接受高剂量化疗前进展并死亡。13 例患者在转移性疾病诊断后中位数 6 个月（范围 4-8 个月）时接受高剂量化疗。10 例患者在首次缓解时无视网膜母细胞瘤，在中位数 103 个月（范围 34-202 个月）的随访中无复发，而 3 例患者（2 例中枢神经系统，1 例下颌骨）在转移性疾病诊断后 14-20 个月复发。5 年无复发生存率和无事件生存率分别为 67%（95%置信区间 38-85%）和 59%（95%置信区间 31-79%）。10 例幸存者中有 6 例接受了放疗。3 例患者在诊断为转移性疾病后 14、4 和 9 年分别发生继发性骨肉瘤。
包括大剂量化疗联合自体造血干细胞挽救在内的强化多模式治疗对大多数接受治疗的 4a 期转移性视网膜母细胞瘤患者是治愈性的。外照射放疗的作用尚不清楚。
