BACKGROUND: Chemoimmunotherapy (ChIt) has been proven to be an effective treatment for patients with refractory high-risk neuroblastoma (HR-NBL). The objective was to assess the appearance of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after high-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) in patients previously treated with ChIt for refractory HR-NBL. METHODS: Nineteen patients were treated with ChIt based on dinutuximab beta for refractory NBL and underwent ASCT. Six patients underwent HDC with ASCT according to the SIOPEN protocol (Busulfan and Melphalan (BuMel)). Treosulfan and Melphalan (TreoMel) were used in 13 patients. The occurrence of VOD/SOS was analysed. The Mann-Whitney U test was used to analyse the correlation between VOD/SOS and potential risk factors. RESULTS: VOD/SOS developed in five out of six patients when BuMel was used after ChIt (3 pts, grade 4; 2 pts, grade 3), resulting in two deaths. No VOD/SOS was observed in patients receiving TreoMel. Other analysed factors had no influence of VOD/SOS occurrence and the only identified risk factor was BuMel administered after ChIt. CONCLUSIONS: Patients with refractory HR-NBL treated with ChIt and DB did not present life-threatening toxicities or severe liver toxicities during the ChIt cycles and continued to HDC with ASCT according to SIOPEN guidelines. The incidence of severe VOD/SOS after ChIt and subsequent BuMel was higher than expected, with severe course resulting in two deaths. Taking into account the possible increase in the risk of VOD/SOS after BuMel used after chemotherapy combined with DB, careful observation with early VOD/SOS treatment in patients after ChIt is recommended and TreoMel regimen may be considered as less toxic.

Background: Accurate evaluation of bone marrow involvement is important for staging and treatment monitoring in pediatric neuroblastoma. This study evaluated flow cytometry for detecting neuroblastoma cells in bone marrow aspirates. Methods: In this prospective exploratory correlative analysis, samples from 28 children were assessed through flow cytometry and cytomorphology; available histopathological and iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy results were compared. Neuroblastoma cells were identified as nucleated CD56⁺CD45⁻CD36⁻CD71⁻ events. Results: Flow cytometry detected neuroblastoma cell populations across a broad quantitative range, including low-level populations. Agreement between flow cytometry and cytomorphology was 90.0% (Cohen’s κ = 0.56). In 16 paired aspirate-level records with at least one positive result, flow cytometric and cytomorphological percentages showed a positive Pearson correlation (r = 0.878, p < 0.0001), although this association was sensitive to one high-value observation. Agreement with histopathology was 92.1–94.8% (κ = 0.59–0.64), whereas agreement with MIBG scintigraphy was slight to fair (κ = 0.12–0.23). Conclusions: Flow cytometry provided rapid, quantitative detection of neuroblastoma cell populations in bone marrow aspirates. It should be considered complementary to cytomorphology and histopathology, as repeated examinations, the limited panel, and the lack of an independent reference standard preclude definitive estimates of diagnostic performance.