28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures.
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.
St Anna Kinderspital, Kinderspitalgasse, Vienna, Austria. ruth.ladenstein@stanna.at
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Ladenstein
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Pötschger
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Hartman
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Pearson
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Klingebiel
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Castel
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Yaniv
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Demirer
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Dini
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005060:Europe / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009447:Neuroblastoma / Q000188:drug therapy / Q000628:therapy*; D012042:Registries; D012074:Remission Induction / Q000379:methods; D014182:Transplantation, Autologous