Measurable residual disease (MRD) surveillance in acute myeloid leukemia (AML) may identify patients destined for relapse and thus provide the option of pre-emptive therapy to improve their outcome. Whilst flow cytometric MRD (Flow-MRD) can be applied to high-risk AML/ myelodysplasia patients, its diagnostic performance for detecting impending relapse is unknown. We evaluated this in a cohort comprising 136 true positives (bone marrows preceding relapse by a median of 2.45 months) and 155 true negatives (bone marrows during sustained remission). At an optimal Flow-MRD threshold of 0.040%, clinical sensitivity and specificity for relapse was 74% and 87% respectively (51% and 98% for Flow-MRD ≥ 0.1%) by ‘different-from-normal’ analysis. Median relapse kinetics were 0.78 log₁₀/month but significantly higher at 0.92 log₁₀/month for FLT3-mutated AML. Computational (unsupervised) Flow-MRD (C-Flow-MRD) generated optimal MRD thresholds of 0.036% and 0.082% with equivalent clinical sensitivity to standard analysis. C-Flow-MRD-identified aberrancies in HLADRlow or CD34+CD38low (LSC-type) subpopulations contributed the greatest clinical accuracy (56% sensitivity, 90% specificity) and notably, by longitudinal profiling expanded rapidly within blasts in > 40% of 86 paired MRD and relapse samples. In conclusion, flow MRD surveillance can detect MRD relapse in high risk AML and its evaluation may be enhanced by computational analysis.

急性髓系白血病 (AML) 的可测量残留病灶 (MRD) 监测可以识别注定会复发的患者，从而提供先发制人的治疗选择，以改善其预后。虽然流式细胞术 MRD (Flow-MRD) 可应用于高危 AML/骨髓增生异常患者，但其检测即将复发的诊断性能尚不清楚。我们在一个队列中对此进行了评估，该队列包括 136 个真阳性（中位复发前的骨髓 2.45 个月）和 155 个真阴性（持续缓解期间的骨髓）。在最佳 Flow-MRD 阈值为 0.040% 时，通过“与正常不同”分析，复发的临床敏感性和特异性分别为 74% 和 87%（Flow-MRD ≥ 0.1% 时为 51% 和 98%）。 FLT3突变 AML 的中位复发动力学为 0.78 log ₁₀ /月，但显着较高，为 0.92 log ₁₀ /月。计算（无监督）Flow-MRD (C-Flow-MRD) 生成的最佳 MRD 阈值为 0.036% 和 0.082%，与标准分析具有同等的临床敏感性。 C-Flow-MRD 识别的 HLADRlow 或 CD34+CD38low（LSC 型）亚群中的异常贡献了最大的临床准确性（56% 敏感性，90% 特异性），值得注意的是，纵向分析在 86 例中的 40% 以上的原始细胞中迅速扩展配对的 MRD 和复发样本。总之，流式 MRD 监测可以检测高危 AML 中的 MRD 复发，并且可以通过计算分析来增强其评估。