1. ¹St Anna Kinderspital, Kinderspitalgasse, Vienna, Austria
2. ²Unit for Studies and Statistics of Integrated Research and Projects, Children's Cancer Research Institute—St Anna Kinderkrebsforschung, Kinderspitalgasse, Vienna, Austria
3. ³Institut Gustave Roussy, Rue Camille Desmoulins, Villejuif, France
4. ⁴Royal Marsden Hospital, The Institute of Cancer Research, Sutton, Surrey, UK
5. ⁵Klinikum der Johann-Wolfgang Goethe Universitaet, Klinik für Kinderheilkunde und Jugendmedizin, Frankfurt am Main, Germany
6. ⁶Hospital Universitario Infantil La Fe, Oncologia Pediatrica, Avenida de Campanar, Valencia, Spain
7. ⁷Schneider Children's Medical Center of Israel, Petach-Tikva, Israel
8. ⁸Ankara University Faculty of Medicine, Cebeci Campus Dirimevi, Ankara, Turkey
9. ⁹Istituto Giannina Gaslini, Largo G Gaslini, Genova, Italy

Correspondence: Professor R Ladenstein, Unit for Studies and Statistics of Integrated Research and Projects, Children's Cancer Research Institute—St Anna Kinderkrebsforschung, Kinderspitalgasse 6, Vienna A-1090, Austria. E-mail: ruth.ladenstein@stanna.at

Abstract

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.