Abstract：
BACKGROUND: Multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS) can both be used to identify a neoplastic clonotype by targeting CDR3 and assessing rearrangements in IgH, IgK, IgL, TCR-β, and TCR-gamma loci. The clonotypic sequence can be robustly used to track minimal residual disease (MRD). The ability to track MRD by NGS in mixed phenotype acute leukemia (MPAL) is unknown and warrants investigation.
METHODS: Institutional Review Board (IRB) approval was obtained. Central Moffitt Cancer Center (MCC) database was searched to locate any patients with MPAL from over 600,000 entries. Patient charts were manually curated to identify those with clonoSEQ data, and clinical data was procured from the electronic medical record (EMR).
RESULTS: Twenty-nine patients with MPAL were identified. Only 2 patients with clonoSEQ testing were found. Both demonstrated a B/myeloid phenotype, and both were bilineal. NGS (clonoSEQ) identified 4 dominant (IGH) (patient A; 8/2019) and 2 dominant sequences (patient B; 10/2019), respectively. In both patients, clonoSEQ testing successfully tracked minimal residual disease and mirrored clinical disease burden.
CONCLUSIONS: This report is the first to confirm the utility of NGS-based MRD tracking in patients with MPAL and shows increased sensitivity of NGS over MRD flow cytometry.
METHODS: Institutional Review Board (IRB) approval was obtained. Central Moffitt Cancer Center (MCC) database was searched to locate any patients with MPAL from over 600,000 entries. Patient charts were manually curated to identify those with clonoSEQ data, and clinical data was procured from the electronic medical record (EMR).
RESULTS: Twenty-nine patients with MPAL were identified. Only 2 patients with clonoSEQ testing were found. Both demonstrated a B/myeloid phenotype, and both were bilineal. NGS (clonoSEQ) identified 4 dominant (IGH) (patient A; 8/2019) and 2 dominant sequences (patient B; 10/2019), respectively. In both patients, clonoSEQ testing successfully tracked minimal residual disease and mirrored clinical disease burden.
CONCLUSIONS: This report is the first to confirm the utility of NGS-based MRD tracking in patients with MPAL and shows increased sensitivity of NGS over MRD flow cytometry.
摘要：
背景：多重聚合酶链反应（PCR）和下一代测序（NGS）均可用于通过靶向CDR3和评估IgH中的重排来鉴定肿瘤克隆型，IgK,IgL,TCR-β,和TCR-γ基因座。克隆型序列可以稳健地用于追踪微小残留病(MRD)。在混合表型急性白血病（MPAL）中通过NGS跟踪MRD的能力未知，值得研究。
方法：获得机构审查委员会（IRB）批准。搜索中央Moffitt癌症中心（MCC）数据库，以从超过600,000个条目中找到任何患有MPAL的患者。手动策划患者图表，以识别具有clonoSEQ数据的患者，临床数据来自电子病历(EMR).
结果：确认了29例MPAL患者。仅发现2名接受clonoSEQ测试的患者。两者都表现出B/髓系表型，而且都是双簧管.NGS（clonoSEQ）确定了4个显性序列（IGH）（患者A;8/2019）和2个显性序列（患者B;10/2019），分别。在这两个病人中，clonoSEQ测试成功追踪了微小残留疾病并反映了临床疾病负担。
结论：该报告首次证实了基于NGS的MRD追踪在MPAL患者中的实用性，并显示NGS比MRD流式细胞术的敏感性更高。
方法：获得机构审查委员会（IRB）批准。搜索中央Moffitt癌症中心（MCC）数据库，以从超过600,000个条目中找到任何患有MPAL的患者。手动策划患者图表，以识别具有clonoSEQ数据的患者，临床数据来自电子病历(EMR).
结果：确认了29例MPAL患者。仅发现2名接受clonoSEQ测试的患者。两者都表现出B/髓系表型，而且都是双簧管.NGS（clonoSEQ）确定了4个显性序列（IGH）（患者A;8/2019）和2个显性序列（患者B;10/2019），分别。在这两个病人中，clonoSEQ测试成功追踪了微小残留疾病并反映了临床疾病负担。
结论：该报告首次证实了基于NGS的MRD追踪在MPAL患者中的实用性，并显示NGS比MRD流式细胞术的敏感性更高。
