| Title: |
Circulating Tumor DNA in Pediatric Mature B‐Cell Non‐Hodgkin Lymphoma for Genotyping and Minimal Disease Monitoring |
| Authors: |
Werner, Jana; Damm‐Welk, Christine; Rohde, Marius; Hundsdörfer, Patrick; Vieth, Simon; Karow, Axel; Barnbrock, Anke; Klapper, Wolfram; Richter, Julia; Koslowski, Carla; Kruppa, Luisa; Alawi, Malik; Alfert, Amelie; Burkhardt, Birgit; Wößmann, Wilhelm; Knörr, Fabian |
| Contributors: |
José Carreras Leukämie-Stiftung; Deutsche Kinderkrebsstiftung; Damp Stiftung |
| Source: |
Pediatric Blood & Cancer ; volume 72, issue 10 ; ISSN 1545-5009 1545-5017 |
| Publisher Information: |
Wiley |
| Publication Year: |
2025 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background 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. Methods 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. Results Concentrations of cfDNA were 2.6–36 × 10 3 haploid genome equivalents/mL plasma (median, 7.8 × 10 3 ). 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. Conclusions 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/pbc.31895 |
| Availability: |
https://doi.org/10.1002/pbc.31895; https://onlinelibrary.wiley.com/doi/pdf/10.1002/pbc.31895 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.5A8B5B8B |
| Database: |
BASE |