Detection of clonotypic DNA in the cerebrospinal fluid as a marker of central nervous system invasion in lymphoma.
Detection of clonotypic DNA in the cerebrospinal fluid as a marker of central nervous system invasion in lymphoma.
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DOI：
10.1182/bloodadvances.2021004512
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发表时间：
2021-12-28
期刊：
影响因子：
7.5
通讯作者：
Dubielecka PM
中科院分区：
文献类型：
--
作者：
Olszewski AJ;Chorzalska AD;Petersen M;Ollila TA;Zayac A;Kurt H;Treaba DO;Reagan JL;Hsu A;Egan PC;Butera J;Niroula R;Vatkevich J;Robison J;Sahin I;Jacob AP;Mullins CD;Dubielecka PM
NGS-MRD 检测在患有实质中枢神经系统受累的淋巴瘤患者的 100% 脑脊液样本中检测到克隆型 DNA。 36% 的新诊断侵袭性淋巴瘤中存在脑脊液中的克隆型 DNA，并且与 29% 的中枢神经系统复发风险相关。实质中枢神经系统（CNS）侵犯的诊断和未来中枢神经系统复发风险的预测是侵袭性淋巴瘤治疗的主要挑战，需要准确的生物标志物来补充临床风险预测因子。为此，我们研究了基于下一代测序 (NGS) 的检测结果，该检测可检测淋巴瘤患者脑脊液 (CSF) 中肿瘤来源 DNA 的克隆型免疫球蛋白基因重排。作为诊断工具，NGS-微小残留病 (NGS-MRD) 检测在 13 名已知 CNS 受累患者的 CSF 样本中 100% 检测到了克隆型 DNA。他们包括 7 名仅患有脑实质疾病的患者，其脑脊液经标准细胞学和流式细胞术检测呈阴性，以及 6 份历史 DNA 等份，中位时间为入组前 39 个月，但使用标准聚合酶链反应未能显示克隆重排。为了进行风险预测，我们前瞻性地收集了 22 名新诊断的 B 细胞淋巴瘤患者的脑脊液，这些患者具有 CNS 复发的高临床风险，其中 8 名患者 (36%) 的脑脊液中可检测到克隆型 DNA。尽管进行了鞘内预防，CSF 阳性检测与诊断后 12 个月内 CNS 复发累积风险为 29% 相关，而 CSF 阴性患者的风险为 0% (P = .045)。这些观察结果表明，克隆型 DNA 的检测有助于诊断侵袭性淋巴瘤中疑似脑实质复发的情况。此外，NGS-MRD 检测可以增强新诊断淋巴瘤患者中枢神经系统复发的临床风险评估，并帮助选择那些可能从中枢神经系统定向预防新方法中获益最多的患者。
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. 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.
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50.5
作者：
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Wu, Y. L.
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Hatton, Chris S. R.