Minimal Residual Disease Detection in Peripheral Blood of Patients With High-Risk Neuroblastoma Correlates With Outcome in the International GPOH-DCOG Prospective Validation Study
Year: 2025
Type: article
Abstract: PURPOSE About 60% of patients with high-risk neuroblastoma relapse. Specific mRNA detection in bone marrow (BM) by reverse transcriptase quantitative PCR (RT-qPCR) is associated with survival outcomes. Peripheral blood (PB) sampling is less invasive. Therefore, we prospectively validated an RT-qPCR panel of neuroblastoma mRNA in PB of patients with high-risk neuroblastoma, treated in NB2004-HR (GPOH) and NBL2009 (DCOG). METHODS From 312 patients, 634 PB samples were prospectively collected (2009-2017) at diagnosis, after two cycles and end-of-induction therapy. RT-qPCR was performed using our panel of neuroblastoma mRNA markers: PHOX2B , TH , DDC , CHRNA3 , and DBH . Results were compared with paired BM samples. The association between neuroblastoma detection and event-free survival (EFS) and overall survival (OS) was estimated using Kaplan-Meier's methodology and multivariable Cox regression model. RESULTS Clear correlation between calculated infiltration by neuroblastoma mRNA expression in PB and BM was seen at diagnosis ( r s 0.70 [95% CI, 0.62 to 0.76]), and heterogeneity was seen after two cycles (0.37 [95% CI, 0.12 to 0.58]) and end of induction (0.61 [95% CI, 0.10 to 0.87]). mRNA expression was significantly lower in PB compared with BM. At diagnosis, PB infiltration ≥1% was a prognostic factor for survival: adjusted hazard ratio (HR) was 2.37 [95% CI, 1.56 to 3.60] for EFS and 2.60 [1.65-4.08] for OS. At the end of induction, PHOX2B positivity in PB samples (n = 11) was associated with poor outcomes: HR 3.06 [1.51-6.20] for EFS and 2.88 [1.36-6.11] for OS. In patients with ≥10% BM infiltration at diagnosis, detection of the mRNA panel in PB samples could significantly distinguish between survival groups; the adjusted HR of PB infiltration ≥1% was 2.09 [1.01-4.30] for OS. CONCLUSION PB infiltration is associated with EFS and OS at diagnosis; it is also significantly associated with survival outcomes of patients with ≥10% BM infiltration at diagnosis. During follow-up, neuroblastoma mRNA detection in PB can be of added value, when BM analysis is not possible.
Source: JCO Precision Oncology
DOI: 10.1200/po-25-00235
Authors: Nina U. Gelineau, Lieke M.J. van Zogchel, Boris De Carolis, Esther M. van Wezel, Lily Zappeij‐Kannegieter, Ahmad Javadi, Roswitha Schumacher‐Kuckelkorn, Thorsten Simon, Frank Berthold, Max M. van Noesel, Marta Fiocco, Janine Stutterheim, C. Ellen van der Schoot, Barbara Hero, Godelieve A.M. Tytgat
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4417475308