Ladenstein R, Pötschger U, Hartman O, Pearson A D J, Klingebiel T, Castel V, Yaniv I, Demirer T, Dini G
St Anna Kinderspital, Kinderspitalgasse, Vienna, Austria.
Bone Marrow Transplant. 2008 Jun;41 Suppl 2:S118-27. doi: 10.1038/bmt.2008.69.
Between 1978 and 2006, the European Group for Blood and Marrow Transplantation registered 4098 high-dose therapy (HDT) procedures followed by stem cell rescue (SCR) (3974 autologous/124 allogeneic) in patients with neuroblastoma. The 5-year rates for overall (OS) and event-free survival are 37 and 32%, respectively. The median age at diagnosis is 3.9 years (0.3-62 years) with 76 patients older than 18 years. Patients above 10 years carry a 2.5-fold higher risk. Younger patients cure significantly (<0.001) better with OS rates of 40 and 30% for age groups 2-4 years and 4-10 years, respectively. Their risks are about twofold higher than that of patients below 2 years with OS rates of 60%. The better the quality of remission status before HDT/SCT the better are the observed OS rates: 43% in CR1 (1199 patients) and 42% for CR2 (140 patients), and 36% for those in very good partial or partial remission (1413 patients) and 21% for those with sensitive relapse (134 patients). Patients reported with stable disease in first remission still had an OS rate of 30%. Multivariate analysis shows significantly better OS in the age group of less than 2 years (<0.0001), as well as a better quality of remission status before HDT/SCT (P<0.0001), with the use of peripheral stem cells (P=0.014), autologous SCT (P=0.031) and busulphan/melphalan HDT (P<0.001). Busulphan/melphalan HDT/SCT in first remission achieves an OS of 48%, while it is only 35% with other regimens (P<0.001), including melphalan alone, other melphalan-containing regimens, a variety of other drugs given as a single HDT as well as the addition of TBI or sequential HDT/SCT procedures. Further progress in the field may only be expected from large-scale international randomized trials.
1978年至2006年间，欧洲血液与骨髓移植组登记了4098例神经母细胞瘤患者接受大剂量治疗（HDT）后进行干细胞救援（SCR）的病例（3974例自体/124例异体）。总生存率（OS）和无事件生存率的5年率分别为37%和32%。诊断时的中位年龄为3.9岁（0.3 - 62岁），其中76例患者年龄超过18岁。10岁以上患者的风险高出2.5倍。年龄较小的患者治愈率显著更高（<0.001），2 - 4岁和4 - 10岁年龄组的OS率分别为40%和30%。他们的风险比2岁以下OS率为60%的患者高出约两倍。HDT/SCT前缓解状态质量越好，观察到的OS率越高：CR1期（1199例患者）为43%，CR2期（140例患者）为42%，非常好的部分缓解或部分缓解期（1413例患者）为36%，敏感复发患者（134例患者）为21%。首次缓解期病情稳定的患者OS率仍为30%。多因素分析显示，年龄小于2岁的年龄组OS显著更好（<0.0001），HDT/SCT前缓解状态质量更好（P<0.0001），使用外周血干细胞（P = 0.014）、自体SCT（P = 0.031）以及白消安/美法仑HDT（P<0.001）。首次缓解期采用白消安/美法仑HDT/SCT的OS为48%，而采用其他方案（P<0.001）时仅为35%，其他方案包括单独使用美法仑、其他含美法仑的方案、作为单一HDT使用的多种其他药物以及添加全身照射或序贯HDT/SCT程序。该领域的进一步进展可能只能通过大规模国际随机试验来实现。
