28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures

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 (o0.001) 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 (o0.0001), as well as a better quality of remission status before HDT/SCT (Po0.0001), with the use of peripheral stem cells (P ¼ 0.014), autologous SCT (P ¼ 0.031) and busulphan/melphalan HDT (Po0.001). Busulphan/melphalan HDT/SCT in first remission achieves an OS of 48%, while it is only 35% with other regimens (Po0.001), 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.

Not too little, not too much—just right! (Better ways to give high dose melphalan)

“…Modern, cisplatin-based chemotherapy provided for relatively poor long-term survival in neuroblastoma, 58 but this result was improved significantly with the addition of a single high-dose of melphalan and HCT. 59 Attempts to intensify the melphalan were associated with what was a high TRM, when this was a 'kill or cure' strategy (Lodenstein et al 60 Figure 1), but a subsequent randomised controlled trial confirmed the value of a melphalan-based combination including TBI, when compared to three courses of intensive multiagent chemotherapy. 61 This study also confirmed the benefit of the randomised addition of retinoid therapy post transplant, confirmed with much longer follow-up.…”

“…63 Figure 1. 100-day TRM and year of high-dose procedure for neuroblastoma (with permission, from Ladenstein et al 60 ).…”

“…Although this approach may appear quite restrictive, these criteria are fulfilled when high-dose melphalan is used in the context of autologous HCT for plasma cell myeloma. Indeed, melphalan, which has been in use for 60 years, has been used in this way for 30 years. One might think we would know all there is to know about the use of this agent for this indication.…”

Hematopoetic stem cell transplantation in children

“…The European Group for Blood and Marrow Transplantation data have shown that transplantation prolongs the course in pediatric cases of neuroblastoma and Ewing tumor (24,58,59). In other solid tumors, the patients may benefit from autologous transplantation in presence of the following special conditions (24): …”

Non-Infectious Early Complications of Allogeneic Stem Cell Transplantations

“…The platelet engraftment is described as the platelet count of 20 x 10 9 / L and above without the support at least for 7 consecutive days. [1][2][3][4] Hemoglobin (Hb) level of more than 8 g / dl without support is regarded as the threshold for red cell engraftment. Graft failure is defined as no evidence of hematopoietic cell engraftment or hematologic recovery following an allo-HSCT.…”