Acute Toxicities and Early Outcomes of Tandem Autologous Stem Cell Transplantation in Pediatric High-Risk Neuroblastoma: A Multicenter Study

High-dose chemotherapy with tandem autologous stem cell transplantation (ASCT) is a standard approach for pediatric high-risk neuroblastoma (HR-NB); however, data on acute regimen-related toxicities are limited. This study evaluated treatment-related toxicities and day +180 outcomes following tandem ASCT in children with HR-NB. We conducted a multi-institutional (n = 13) retrospective review including pediatric patients with HR-NB scheduled for tandem ASCT between January 2014 and June 2021. Descriptive analyses were performed to evaluate organ toxicities and transplantation-related outcomes, focusing on endothelial injury. A total of 255 patients underwent ASCT 1 with thiotepa/cyclophosphamide (TT/Cy). Fourteen patients were unable to proceed to ASCT 2, owing to death in 9, with underlying disease relapse the cause of death in 7 of these 9 (78%). Severe endothelial toxicities, including veno-occlusive disease (VOD) and transplantation-associated thrombotic microangiopathy (TA-TMA) in 3 patients, prevented progression to tandem ASCT. The remaining 241 patients (94.5%) completed tandem ASCT with TT/Cy and carboplatin/etoposide/melphalan. Post-ASCT 2 complications included bloodstream infections (17%), intensive care unit admission (20%), respiratory failure requiring intubation (12%), pulmonary hypertension (4%), and acute kidney injury (18%), with 5% requiring dialysis. VOD occurred in 9% of patients, and TA-TMA occurred in 16% of patients completing tandem ASCT. Six-month survival was 94% for the tandem ASCT recipients. This study highlights the impact of regimen-related toxicities in pediatric HR-NB patients undergoing tandem ASCT. Despite a modest 6-month mortality rate, the burden of endotheliopathies contributed to morbidity and mortality post-ASCT 2. Improved screening and early intervention strategies may help mitigate transplantation-related morbidity.