Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.

We determined whether quantifying neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory neuroblastoma. mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in bone marrow and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold, Δ, for the geometric mean of genes from the TaqMan Low Density Array NB5 assay) and morphologically defined tumor cell percentage in bone marrow, I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined. Time-dependent covariate Cox regression was used to analyze the relationship between Δ and progression-free survival (PFS). NB-mRNA was detectable in 83% of bone marrow (185/223) and 63% (89/142) of blood specimens, and their Δ values were correlated (Spearman = 0.67, < 0.0001), although bone marrow was 7.9 ± 0.5 stronger than blood When bone marrow morphology, MIBG, or CT/MRI were positive, NB-mRNA was detected in 99% (99/100), 88% (100/113), and 81% (82/101) of bone marrow samples. When all three were negative, NB-mRNA was detected in 55% (11/20) of bone marrow samples. Bone marrow NB-mRNA correlated with bone marrow morphology or MIBG positivity ( < 0.0001 and = 0.007). Bone marrow and blood Δ values correlated with PFS ( < 0.001; = 0.001) even when bone marrow was morphologically negative ( = 0.001; = 0.014). Multivariate analysis showed that bone marrow and blood Δ values were associated with PFS independently of clinical disease and gene status ( < 0.001; = 0.055). This five-gene NB5 assay for NB-mRNA improves definition of disease status and correlates independently with PFS in relapsed/refractory neuroblastoma. .