背景:评估可测量的残留病(MRD)是B淋巴细胞白血病(B-ALL)的重要预后工具。在这项研究中,我们评估了基于下一代测序(NGS)的MRD评估在实际临床实践中的实用性.
方法:该研究包括2017年1月至2022年6月在我们机构接受治疗的93例B-ALL儿科患者。在诊断时获得的大多数骨髓样本(91/93,97.8%)中鉴定出IGH或IGK重排的克隆性。
结果:在421个监测样本中,NGS和多参数流式细胞术之间的一致性为74.8%,NGS和逆转录PCR之间的一致性为70.7%。单独的IGH克隆数量升高(P<0.001;危险比[HR],22.2;95%置信区间[CI],7.1-69.1),单独IGK(P=0.011;HR,5.8;95%CI,1.5-22.5),和IGH或IGK(P<0.001;HR,7.2;95%CI,2.6-20.0)与复发风险增加相关。在NGS中检测到新克隆也与无复发生存率低相关(P<0.001;HR,18.1;95%CI,3.0-108.6)。多变量分析证实了诊断时的年龄,BCR::ABL1样突变,TCF3::PBX1突变,以及在监测期间IGH或IGK克隆的数量增加是不利因素。
结论:结论:本研究强调了基于NGS的MRD作为儿童B-ALL患者预后的常规评估工具的实用性.
BACKGROUND: Assessment of measurable residual disease (MRD) is an essential prognostic tool for B-lymphoblastic leukaemia (B-ALL). In this study, we evaluated the utility of next-generation sequencing (NGS)-based MRD assessment in real-world clinical practice.
METHODS: The study included 93 paediatric patients with B-ALL treated at our institution between January 2017 and June 2022. Clonality for IGH or IGK rearrangements was identified in most bone marrow samples (91/93, 97.8%) obtained at diagnosis.
RESULTS: In 421 monitoring samples, concordance was 74.8% between NGS and multiparameter flow cytometry and 70.7% between NGS and reverse transcription-PCR. Elevated quantities of clones of IGH alone (P < 0.001; hazard ratio [HR], 22.2; 95% confidence interval [CI], 7.1-69.1), IGK alone (P = 0.011; HR, 5.8; 95% CI, 1.5-22.5), and IGH or IGK (P < 0.001; HR, 7.2; 95% CI, 2.6-20.0) were associated with an increased risk of relapse. Detection of new clone(s) in NGS was also associated with inferior relapse-free survival (P < 0.001; HR, 18.1; 95% CI, 3.0-108.6). Multivariable analysis confirmed age at diagnosis, BCR::ABL1-like mutation, TCF3::PBX1 mutation, and increased quantity of IGH or IGK clones during monitoring as unfavourable factors.
CONCLUSIONS: In conclusion, this study highlights the usefulness of NGS-based MRD as a routine assessment tool for prognostication of paediatric patients with B-ALL.