Circulating Tumor DNA in Pediatric Mature B-Cell Non-Hodgkin Lymphoma for Genotyping and Minimal Disease Monitoring

Early detection of treatment failure in pediatric patients with mature B-cell non-Hodgkin lymphoma (NHL) could improve treatment stratification. Analysis of circulating tumor DNA (ctDNA) has been established as a biomarker in adult patients with mature B-cell NHL (B-NHL); however, data on ctDNA in pediatric mature B-NHL are lacking.

We investigated genotyping and disease monitoring in initial plasma cell-free DNA (cfDNA) by targeted, normal-matched sequencing in 19 pediatric patients with mature B-NHL, 16 of whom had Burkitt lymphoma or leukemia. Matching lymphoma DNA was available in 18 patients.

Concentrations of cfDNA were 2.6-36 × 10³ haploid genome equivalents/mL plasma (median, 7.8 × 10³). In 10 patients with high-risk disease (risk groups R3 and R4), 60% of somatic short variants were detected in both plasma and lymphoma samples using a tumor-agnostic approach, whereas 26% and 14% were identified in DNA from lymphoma or plasma samples only. In 4/10 patients with high-risk disease, eight non-silent variants were identified only in the plasma samples. In patients with low-risk disease, 27% of mutations were shared in plasma and tumor; 65% and 8% were detected in DNA from lymphoma or plasma samples only. In a tumor-informed approach, ctDNA was detectable in 16/18 plasma samples with a proportion of 0.045%-55%, demonstrating its potential for minimal disease monitoring.

Non-invasive genotyping from a plasma sample is feasible in high-risk pediatric mature B-cell lymphoma patients. Our findings provide the basis for investigating the clinical utility of non-invasive lymphoma genotyping and disease monitoring in pediatric mature B-NHL.