The evaluation of minimal disseminated disease in the bone marrow of children with Burkitt lymphoma using next generation sequencing

Abstract

The effectiveness of treatment for children with B-cell non-Hodgkin lymphomas (B-NHL) has reached 85–90% after the introduction of modern risk-adapted treatment regimens that involve risk group stratification based on tumor stage. Bone marrow involvement is traditionally evaluated using quantitative morphological analysis of tumor cells which has, however, a lower sensitivity compared to molecular genetic methods. In our study, we used next generation sequencing (NGS) to identify tumor-specific V-(D)/J-rearrangements of immunoglobulin genes which can be used as a marker for the evaluation of minimal disseminated disease (MDD) in children with B-NHL. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Here we demonstrated that NGS allows detection of bone marrow involvement at a sensitivity of 10–6 in patients with Burkitt lymphoma, in whom standard morphological analysis failed to reveal the presence of tumor cells. The detection of molecular MDD can improve tumor staging and risk stratification in children with B-cell non-Hodgkin lymphomas.