成年AML患者异基因造血干细胞移植后第+100天及之后复发的可测残留病（MRD）预测价值

Measurable residual disease as predictor of post-day +100 relapses after allografting in adult AML

Blood Advances

影响因子:7.1

分区:医学1区 Top / 血液学2区

发表日期:2025 Feb 11

作者: Naveed Ali, Megan Othus, Eduardo Rodríguez-Arbolí, Corentin Orvain, Filippo Milano, Brenda M Sandmaier, Chris Davis, Ryan S Basom, Frederick R Appelbaum, Roland B Walter

DOI: 10.1182/bloodadvances.2024013214

摘要

多参数流式细胞术（MFC）检测的可测残留病（MRD）在异基因造血干细胞移植（HCT）前能识别高风险AML复发患者，这些复发常在移植后早期发生。为评估MFC MRD检测预测后续复发的作用，我们分析了935例AML或骨髓发育不良性疾病/AML患者，这些患者在首次或第二次形态学缓解状态下接受HCT，并在HCT后第70至100天之间进行骨髓复查，且在第+100天仍存活且未复发。其中136例（15%）在HCT前检测到MRD，只有11例（1%）在第+70至+100天检测到MRD。在第+100天的标志性分析中，HCT前和第+70至+100天的MFC MRD均与复发（均P<0.001）、无进展生存期（PFS；均P<0.001）、总生存期（OS；均P<0.001）以及移植后非复发死亡（P=0.001）相关。值得注意的是，尽管有92%的患者（126/136）在HCT前检测到MRD，但在第+70至+100天时多已转为MRD阴性，其预后仍低于HCT前和第+70至+100天均无MRD的患者，3年复发风险为40%对比15%（P<0.001），3年无进展生存率为50%对比72%（P<0.001），3年总生存率为56%对比76%（P<0.001），但非复发死亡率无显著差异（P=0.53）。因此，尽管MRD转换率较高，但MRD阳性转阴的患者预后仍差于MRD阴性患者，提示所有在HCT前检测到MRD的患者都应考虑进行预防性治疗。

Abstract

Measurable residual disease (MRD) by multiparametric flow cytometry (MFC) before allogeneic hematopoietic cell transplantation (HCT) identifies patients at high risk of acute myeloid leukemia (AML) relapse, often occurring early after allografting. To examine the role of MFC MRD testing to predict later relapses, we examined 935 adults with AML or myelodysplastic neoplasm/AML transplanted in first or second morphologic remission who underwent bone marrow restaging studies between day 70 and 100 after HCT and were alive and without relapse by day +100. Of 935 adults, 136 (15%) had MRD before HCT, whereas only 11 (1%) had MRD at day +70 to +100. In day +100 landmark analyses, pre-HCT and day +70 to +100 MFC MRD were both associated with relapse (both P < .001), relapse-free survival (RFS; both P < .001) overall survival (OS; both P < .001), and, for post-HCT MRD, nonrelapse mortality (P = .001) after multivariable adjustment. Importantly, although 126/136 patients (92%) with MRD before HCT tested negative for MRD at day +70 to +100, their outcomes were inferior to those without MRD before HCT and at day +70 to +100, with 3-year relapse risk of 40% vs 15% (P < .001), 3-year RFS of 50% vs 72% (P < .001), and 3-year OS of 56% vs 76% (P < .001), whereas 3-year nonrelapse mortality estimates were similar (P = .53). Thus, despite high MRD conversion rates, outcomes MRD positive/MRD negative (MRDneg) patients are inferior to those of MRDneg/MRDneg patients, suggesting all patients with pre-HCT MRD should be considered for preemptive therapies after allografting.