Minimal Disease Detection by Immunoglobulin High-Throughput Sequencing in Pediatric Burkitt Lymphoma

To improve upon currently insufficient risk stratification criteria for refining risk-directed therapy for pediatric Burkitt lymphoma (BL), we tested the utility of high-throughput sequencing (HTS) of clonal immunoglobulin (Ig) gene rearrangements for detecting BL minimal marrow disease (MMD). We defined clonal Ig gene rearrangements in diagnostic BL tumor samples from 11 patients. Using Ig HTS of paired, pre-treatment bone marrow (BM) samples from 8 patients, we confirmed MMD detection in all 3 patients with confirmed or indeterminate clinically-defined BM involvement, as well as in 4 of 5 patients negative for clinically-defined BM involvement. These findings establish the feasibility of Ig HTS for sensitive detection of BL MMD and suggest a role for exploring its prognostic relevance.