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鉴定急性髓系白血病中基于白血病相关免疫表型的个体化微小残留病及其预后意义。

Identifying leukemia-associated immunophenotype-based individualized minimal residual disease in acute myeloid leukemia and its prognostic significance.

机构信息

State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, 197 Rui Jin Road II, Shanghai, China.

出版信息

Am J Hematol. 2019 May;94(5):528-538. doi: 10.1002/ajh.25431. Epub 2019 Feb 21.

DOI:10.1002/ajh.25431
PMID:30734356
Abstract

Based on the leukemia-associated immunophenotypes (LAIPs), minimal residual disease (MRD) related to the outcome can be detected by multiparameter flow cytometry in acute myeloid leukemia (AML) patients. Although 0.1% was commonly used as a cutoff value, measurable MRD or MRD level below 0.1% has also been associated with prognostic significance and more sensitive thresholds (<0.1%) are required for improving AML prognosis prediction. In this study, 292 adult patients diagnosed with AML (non-M3) were enrolled, 36 kinds of LAIPs were identified, and the baseline expression levels in normal or regenerating bone marrows of each kind of LAIP were established, which ranged from <2.00 × 10 to 5.71 × 10 . The baseline level of each LAIP was considered as the individual threshold for MRD assessment. MRD statuses stratified by 0.1% and individual threshold were termed as 0.1%-MRD and individual-MRD, respectively. The patients of individual-MRD showed significantly better survival compared with those of 0.1%-MRD /individual-MRD or 0.1%-MRD . Multivariate analysis showed that when time points of complete remission, post the first and second consolidation courses, were considered, only individual-MRD post second consolidation presented independent prognostic value. Notably, in patients of cytogenetic/molecular low-risk (LR) or intermediate-risk (IR), the individual-MRD status could identify the patients with significantly different outcomes, while 0.1%-MRD status could not. Furthermore, among the patients of the LR or IR group which received chemotherapy only, those with individual-MRD status presented favorable survival, which was comparable with that of the patients accepted allogeneic hematopoietic stem cell transplantation (ASCT). This approach is useful in the selection of an ASCT strategy for clinical practice.

摘要

基于白血病相关免疫表型 (LAIPs),通过多参数流式细胞术可在急性髓系白血病 (AML) 患者中检测到与预后相关的微小残留病 (MRD)。尽管通常将 0.1%用作截止值,但可测量的 MRD 或 MRD 水平低于 0.1%也与预后意义相关,并且需要更敏感的阈值 (<0.1%) 来提高 AML 预后预测的准确性。在这项研究中,共纳入了 292 名成人 AML(非 M3)患者,鉴定了 36 种 LAIP,并建立了每种 LAIP 在正常或再生骨髓中的基线表达水平,范围从 <2.00 × 10 到 5.71 × 10 。每种 LAIP 的基线水平被认为是 MRD 评估的个体阈值。根据 0.1%和个体阈值分层的 MRD 状态分别称为 0.1%-MRD 和个体-MRD。与 0.1%-MRD/个体-MRD 或 0.1%-MRD 相比,个体-MRD 的患者生存情况明显更好。多变量分析显示,当考虑完全缓解时间点、第一次巩固治疗后和第二次巩固治疗后时,仅第二次巩固治疗后的个体-MRD 具有独立的预后价值。值得注意的是,在细胞遗传学/分子学低风险 (LR) 或中风险 (IR) 的患者中,个体-MRD 状态可以识别出具有明显不同结局的患者,而 0.1%-MRD 状态则不能。此外,在仅接受化疗的 LR 或 IR 组患者中,具有个体-MRD 状态的患者具有良好的生存情况,与接受异基因造血干细胞移植 (ASCT) 的患者相当。这种方法有助于在临床实践中选择 ASCT 策略。

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