Minimal Residual Disease is a Prognostic Marker for Neuroblastoma With Bone Marrow Infiltration

Objective: This pilot study focused on whether flow cytometry (FCM) detection of minimal residual disease in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma (NB). Patients and Methods: Fifty-seven stage 4 NB patients with BM infiltration were enrolled in this study. All of them received NB-2001 protocol. BM samples were examined for tumor cell contamination by both morphology and FCM with CD45-FITC-/CD81-PE+/CD56-PECy5(+) monoclonal antibodies cocktail at diagnosis and after 4 courses of chemotherapy. Results: BM samples of all patients were positive at diagnosis by FCM, and samples from 30 patients became negative after 4 courses of chemotherapy, 10 patients relapsed (33.3%) in mean 45.5 months, range 7 to 69. Another 27 patients remained positive, and 20 of them relapsed (74.1%) in mean 24.2 months, range 8 to 48. There was a statistically significant difference in event-free survival between the 2 groups (P = 0.002). Conclusions: Persistence of minimal residual disease in BM may work as a chemotherapy response marker and predict the prognosis in advanced NB.