Detection of clonotypic DNA in the cerebrospinal fluid as a marker of central nervous system invasion in lymphoma
| Autor: | Andrew R. Hsu, Pamela C Egan, Diana O. Treaba, Max Petersen, James N. Butera, Rabin Niroula, Adam J. Olszewski, Anna Chorzalska, Patrycja M. Dubielecka, John L. Reagan, Thomas A Ollila, Adam Zayac, John Vatkevich, Jordan Robison, Ilyas Sahin, Chelsea D. Mullins, Habibe Kurt, Allison P. Jacob |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Central Nervous System
Pathology medicine.medical_specialty Lymphoma B-Cell Clinical Trials and Observations Central nervous system Aggressive lymphoma Flow cytometry law.invention chemistry.chemical_compound Cerebrospinal fluid law Cytology hemic and lymphatic diseases Medicine Humans Polymerase chain reaction medicine.diagnostic_test business.industry Lymphoma Non-Hodgkin Hematology DNA medicine.disease Lymphoma medicine.anatomical_structure chemistry business Biomarkers |
| Zdroj: | Blood Advances |
| ISSN: | 2473-9537 2473-9529 |
| Popis: | Key Points The NGS-MRD assay detected clonotypic DNA in 100% of CSF samples from patients who had lymphoma with parenchymal CNS involvement.Clonotypic DNA in CSF was present in 36% of newly diagnosed aggressive lymphomas and was associated with a 29% risk of CNS recurrence. Visual Abstract The diagnosis of parenchymal central nervous system (CNS) invasion and prediction of risk for future CNS recurrence are major challenges in the management of aggressive lymphomas, and accurate biomarkers are needed to supplement clinical risk predictors. For this purpose, we studied the results of a next-generation sequencing (NGS)–based assay that detects tumor-derived DNA for clonotypic immunoglobulin gene rearrangements in the cerebrospinal fluid (CSF) of patients with lymphomas. Used as a diagnostic tool, the NGS-minimal residual disease (NGS-MRD) assay detected clonotypic DNA in 100% of CSF samples from 13 patients with known CNS involvement. They included 7 patients with parenchymal brain disease only, whose CSF tested negative by standard cytology and flow cytometry, and 6 historical DNA aliquots collected from patients at a median of 39 months before accession, which had failed to show clonal rearrangements using standard polymerase chain reaction. For risk prognostication, we prospectively collected CSF from 22 patients with newly diagnosed B-cell lymphomas at high clinical risk of CNS recurrence, of whom 8 (36%) had detectable clonotypic DNA in the CSF. Despite intrathecal prophylaxis, a positive assay of CSF was associated with a 29% cumulative risk of CNS recurrence within 12 months of diagnosis, in contrast with a 0% risk among patients with negative CSF (P = .045). These observations suggest that detection of clonotypic DNA can aid in the diagnosis of suspected parenchymal brain recurrence in aggressive lymphoma. Furthermore, the NGS-MRD assay may enhance clinical risk assessment for CNS recurrence among patients with newly diagnosed lymphomas and help select those who may benefit most from novel approaches to CNS-directed prophylaxis. |
| Databáze: | OpenAIRE |
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