Minimal Disease Monitoring in Pediatric Non-Hodgkin’s Lymphoma: Current Clinical Application and Future Challenges

Abstract

Simple Summary Minimal residual disease (MRD) describes the detection of a few remaining malignant cells in blood or bone marrow with molecular methods or flow cytometry. The detection of MRD in patients with leukemia during therapy indicates the risk of relapse. Its use for treatment stratification is state of the art in all modern leukemia treatment protocols. In pediatric non-Hodgkin lymphoma patients, minimal amounts of tumor cells, so-called minimal disseminated disease (MDD), can often be detected in blood or bone marrow at diagnosis. In children with ALK-positive anaplastic large cell lymphoma, MDD and MRD detected in the blood or bone marrow is associated with high relapse risk. For patients with Burkitt lymphoma or -leukemia or lymphoblastic lymphoma, the meaning of MDD and MRD is less clear. This review summarizes the current knowledge, techniques, application, and challenges in minimal disease detection in pediatric non-Hodgkin lymphoma. Abstract Minimal residual disease (MRD) detection is established routine practice for treatment stratification in leukemia and used for treatment optimization in adult lymphomas. Minimal disease studies in childhood non-Hodgkin lymphomas are challenged by stratified treatment in different subtypes, high cure rates, low patient numbers, limited initial tumor material, and early progression. Current clinical applications differ between the subtypes. A prognostic value of minimal disseminated disease (MDD) could not yet be clearly established for lymphoblastic lymphoma using flow cytometry and PCR-based methods for T-cell receptor (TCR) or immunoglobulin (IG) rearrangements. MYC–IGH fusion sequences or IG rearrangements enable minimal disease detection in Burkitt lymphoma and -leukemia. An additional prognostic value of MDD in Burkitt lymphoma and early MRD in Burkitt leukemia is implicated by single studies with risk-adapted therapy. MDD and MRD determined by PCR for ALK-fusion transcripts are independent prognostic parameters for patients with ALK-positive anaplastic large cell lymphoma (ALCL). They are introduced in routine clinical practice and used for patient stratification in clinical studies. Early MRD might serve as an endpoint for clinical trials and for guiding individual therapy. Validation of MDD and MRD as prognostic parameters is required for all subtypes but ALCL. Next-generation sequencing-based methods may provide new options and applications for minimal disease evaluation in childhood lymphomas.