Background: The HR-NBL-1/SIOPEN trial for patients with high-risk neuroblastoma includes consolidation with high-dose chemotherapy (HDC) for patients achieving an adequate response to induction chemotherapy. Bone marrow reconstitution after HDC is with reinfusion of autologous peripheral blood stem cells (PBSCs) or, less commonly, bone marrow-derived cells (BMSCs). Data relating to engraftment have not previously been reported in detail, but are important to establish a baseline for quality assurance of autografts performed at individual centres and to correlate with outcome.
Methods: Data were obtained from the SIOPEN-R-NET trial database. Only patients who received BuMel MAT were included. Neutrophil engraftment was determined as the time to ANC>0.5x109/L (irrespective of G-CSF administration) and platelet recovery to >20 or >50x109/L (transfusion independent). Kaplan-Meier estimates of event-free and overall survival were calculated from day of cell reinfusion and curves compared using log-rank test.
Results: Data were available for 1226 patients. Overall median time to ANC recovery was 12 days, and 20 or 35 days for platelets >20x109/L or >50x109/L respectively. 1164 (95%) patients had ANC recovery by day 30. 17 (1.4%) died within 150 days without ANC engraftment. ANC and platelet engraftment did not vary depending on year of procedure, route of busulfan administration (oral/IV), or body weight (12kg cut-off). Engraftment was significantly delayed in patients in whom fewer than 3x106/kg PBSC/BMSC had been harvested (D30 ANC engraftment in 90±3% of patients vs 96±1%, p=0.005). Patients without ANC engraftment by D30 (n=59, 5%) had poorer 5-year survival (EFS 38±7% vs 44±2%, p=0.042; OS 42±7% vs 52±2%, p=0.006), with a significantly increased risk of early non-relapse mortality (5-year NRM 10±4% vs 3±1%, p<0.0001). These effects will be further explored in a multivariable analysis.
Conclusion: These data confirm a clear baseline for successful engraftment post-BuMel HDC. Delayed engraftment is associated with poorer survival emphasising the importance of ongoing quality assurance of autograft programmes and cautioning against proceeding with HDC with inadequate PBSC/BMSC harvest.