Monitoring of bone marrow minimal residual disease combined with genetic analysis identifies different risk groups in stage M neuroblastoma patients

Background:

Disseminated tumor cells (DTCs) are frequently found at diagnosis in the bone marrow (BM) of stage M neuroblastoma (NB) patients (pts) and evaluation at different time points during therapy is considered an excellent tool for disease monitoring. We hypothesized that highly sensitive/specific DTC detection/quantification plus genomic information can identify a prognostic/predictive impact.

Methods:

DTC content of BM samples from stage M NB pts (obs. cohort: n = 43; val. cohort: n = 100) was quantified using an automated scanning/analysis device (GD₂ immunofluorescence + FISH) with a sensitivity of detecting 1 DTC among 10⁶ mononuclear cells (MNCs).

Results:

Complete BM clearing after induction phase correlated with a significantly better 5-year EFS (obs. cohort: 80 ± 13% vs. 36 ± 13% [p = 0.025]; val. cohort: 60 ± 11% vs. 20 ± 6% [p < 0.001]). Even small infiltration rates (e.g. < 25 DTCs per million MNCs), were identified as being prognostically relevant. ATRX ^del, TERT ^aberr, 1q^aberr, 4 p^del and 17 p^del and 19q^del negatively influenced outcome, superimposing clearing status.

Conclusion:

Our results depict the importance of molecular MRD monitoring combined with genomic data in stage M NB pts resulting in well separated subgroups.

 

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No conflict of interest has been declared by the author(s).