可测量的残留疾病，作为成年AML同差后日后复发的预测因子
Measurable residual disease as predictor of post-day +100 relapses after allografting in adult AML
影响因子:7.10000
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
摘要
在同种异体造血细胞移植（HCT）之前，通过多参数流式细胞术（MFC）可测量的残留疾病（MRD）确定了急性骨髓性白血病（AML）复发的高风险，通常发生在同疗后早期。为了检查MFC MRD测试在预测后期复发中的作用，我们检查了935名患有AML或骨髓增生性肿瘤/AML的成年人，在第一或第二次形态学缓解中移植了，他们在HCT和HCT之间进行了第70和100天之间的骨髓恢复研究，并且在HCT之后，并在+100 +100 +100天还活着，没有复发。在935名成年人中，有136名（15％）在HCT之前拥有MRD，而11（1％）的MRD在第+70至+100之前。在第+100天的地标分析中，前HCT和+70至+100 MFC MRD都与复发有关（P <.001），无复发的生存率（RFS; P <.001）的总生存期（OS; P <.001），均为P <.001），并且对于HCT MRD MRD，NORD MRD，NORD，NORDERLAPSE，NOTRELAPSE MUTER（p = .001），后者是多次调整后的。重要的是，尽管HCT前的126/136例患者（92％）在+70至+100的HCT之前测试了MRD阴性，但他们的预后不如HCT之前没有MRD的患者，在HCT之前没有MRD，在+70至+100的情况下，3年复发风险为40％，40％vs 15％（P <.001）（P <.001），3年vs 72％（p <。 76％（p <.001），而3年的非归因死亡率估计值相似（p = .53）。因此，尽管MRD转化率很高，但预后MRD阳性/MRD阴性（MRDNEG）患者均低于MRDNEG/MRDNEG患者的患者，这表明所有HCT MRD患者均应考虑所有患有前HCT MRD的患者。
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.