Feasibility of IG and TCR rearrangements quantification in ctDNA for monitoring clinical response in pediatric lymphomas

Introduction Lymphomas are malignancies of the lymphatic system characterized by clonal rearrangements of immunoglobulin (Ig) and T-cell receptor (TCR) genes. While diagnosis relies on tissue biopsy, circulating tumor DNA (ctDNA) analysis offers a minimally invasive approach for real-time disease monitoring. This study evaluated next-generation sequencing (NGS) for the detection and quantification of Ig and TCR rearrangements in ctDNA from pediatric lymphoma patients. Methods Forty cases (21 Hodgkin and 19 non-Hodgkin lymphomas) were analyzed using NGS with BIOMED-2 and EuroClonality primers. Results Clonal rearrangements were identified in tumor DNA from 23 patients, yielding 54 rearrangements. For 19 patients, paired tumor (gDNA) and plasma (cfDNA) at diagnosis samples were analyzed. Most of the rearrangements identified in these tumor samples (n = 48) were found in the corresponding diagnostic cfDNA (n = 43, 89.6%). Patients who relapsed showed significantly higher cfDNA levels at diagnosis, and in one case, ctDNA increase preceded clinical or radiological relapse. Discussion These findings support liquid biopsy as a feasible tool for monitoring disease dynamics and early relapse detection in pediatric lymphoma.