Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China.
Cancer Med. 2019 Sep;8(12):5459-5467. doi: 10.1002/cam4.2422. Epub 2019 Jul 30.
Acute myeloid leukemia (AML) with t(8;21) is a heterogeneous disease. Although the detection of minimal residual disease (MRD), which is indicated by RUNX1-RUNX1T1 transcript levels, plays a key role in directing treatment, risk stratification needs to be improved, and other markers need to be assessed. A total of 66 t(8;21) AML patients were tested for aldehyde dehydrogenase (ALDH) activity by flow cytometry at diagnosis, and 52 patients were followed up for a median of 20 (1-34) months. The median percentage of CD34+ALDH+, CD34+CD38-ALDH+, and CD34+CD38+ALDH+ cells among nucleated cells were 0.028%, 0.012%, and 0.0070%, respectively. The CD34+ALDH+-H, CD34+CD38-ALDH+-H, and CD34+CD38+ALDH+-H statuses (the percentage of cells that were higher than the individual cutoffs) were all significantly associated with a lower 2-year relapse-free survival (RFS) rate in both the whole cohort and adult patients (P = .015, .016, and .049; P = .014, .018, and .032). Patients with < 3-log reduction in the RUNX1-RUNX1T1 transcript level after the second consolidation therapy (defined as MRD-H) had a significantly lower 2-year RFS rate than patients with ≥ 3-log reduction (MRD-L) (P = .017). The CD34+ALDH+ status at diagnosis was then combined with the MRD status. CD34+ALDH+-L/MRD-H patients had similar 2-year RFS rates to both CD34+ALDH+-L/MRD-L and CD34+ALDH+-H/MRD-L patients (P = .50 and 1.0); and CD34+ALDH+-H/MRD-H patients had significantly lower 2-year RFS rate compared with CD34+ALDH+-L and/or MRD-L patients (P < .0001). Multivariate analysis showed that CD34+ALDH+-H/MRD-H was an independent adverse prognostic factor for relapse. In conclusion, ALDH status at diagnosis may improve MRD-based risk stratification in t(8;21) AML, and concurrent high levels of CD34+ALDH+ at diagnosis and MRD predict relapse.
急性髓系白血病伴 t(8;21) 是一种异质性疾病。尽管检测最小残留疾病（MRD），其由 RUNX1-RUNX1T1 转录水平表示，在指导治疗中起着关键作用，但需要进行风险分层，还需要评估其他标志物。在诊断时，通过流式细胞术对 66 例 t(8;21) 急性髓系白血病患者的醛脱氢酶（ALDH）活性进行了检测，52 例患者接受了中位数为 20（1-34）个月的随访。核细胞中 CD34+ALDH+、CD34+CD38-ALDH+和 CD34+CD38+ALDH+细胞的中位数百分比分别为 0.028%、0.012%和 0.0070%。CD34+ALDH+-H、CD34+CD38-ALDH+-H 和 CD34+CD38+ALDH+-H 状态（高于个体截止值的细胞百分比）在整个队列和成年患者中均与较低的 2 年无复发生存率（RFS）显著相关（P=.015，.016 和.049；P=.014，.018 和.032）。第二次巩固治疗后 RUNX1-RUNX1T1 转录水平降低 3 个对数级以上（定义为 MRD-H）的患者与降低 3 个对数级以上（MRD-L）的患者相比，2 年 RFS 率显著降低（P=.017）。然后将诊断时的 CD34+ALDH+状态与 MRD 状态相结合。与 CD34+ALDH+-L/MRD-H 患者相比，CD34+ALDH+-L/MRD-L 和/或 CD34+ALDH+-H/MRD-L 患者的 2 年 RFS 率相似（P=.50 和 1.0）；而 CD34+ALDH+-H/MRD-H 患者的 2 年 RFS 率明显低于 CD34+ALDH+-L 和/或 MRD-L 患者（P<.0001）。多变量分析表明，CD34+ALDH+-H/MRD-H 是复发的独立不良预后因素。总之，诊断时的 ALDH 状态可能会改善 t(8;21) 急性髓系白血病中基于 MRD 的风险分层，同时高水平的 CD34+ALDH+在诊断时和 MRD 预测复发。
