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

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.

Quantification of Minimal Disease by Digital PCR in ALK-Positive Anaplastic Large Cell Lymphoma: A Step towards Risk Stratification in International Trials?

“…Measurement of qualitative MDD in BM and PB has evolved to a routine staging procedure for patients with ALK-positive ALCL [ 13 , 14 ]. MRD assessment in PB after one course of chemotherapy as well as further during therapy in positive patients belongs to routine restaging, as well [ 14 , 15 ].…”

“…Measurement of qualitative MDD in BM and PB has evolved to a routine staging procedure for patients with ALK-positive ALCL [ 13 , 14 ]. MRD assessment in PB after one course of chemotherapy as well as further during therapy in positive patients belongs to routine restaging, as well [ 14 , 15 ]. These parameters are now used as inclusion criteria or for patient stratification in clinical trials (ALCL-VBL EudraCT: 2017-002935-40, Briga-Ped: NCT04925609).…”

Pediatric Anaplastic Large Cell Lymphoma with Concomitant Involvement of Spine and Central Nervous System: A Case Report and Review of Literature

“…Furthermore, MRD at the end of treatment could identify high-risk patients for whom consolidation therapy could be added to prevent relapse and increase the chances of survival in children who are at a very high risk of relapse [44]. Next-generation sequencingbased methods may represent new opportunities for minimal disease evaluation in childhood ALCL and other lymphoma subtypes [45]. Up to now, MRD has not been studied to evaluate if it can replace bioptic procedures or post-therapy radiological disease monitoring.…”

Clinical Perspectives for 18F-FDG PET Imaging in Pediatric Oncology: Μetabolic Tumor Volume and Radiomics

“…Thus, MDD assessment in bone marrow or peripheral blood, by FISH (fluorescence in situ hybridization) or PCR (polymerase chain reaction) analysis, is reported as additional information in the revised international pediatric NHL staging system (IPNHLSS) [ 77 ]. Although stage-dependent, MDD is considered an additional tool for the prognosis and evaluation of response to treatment [ 118 ]. Both PET/CT imaging and molecular techniques (FISH and PCR) for the assessment of minimal residual disease (MRD) are included in the international response criteria for pediatric NHL [ 119 ].…”