Abstract
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.
Highlights
T(8;21) acute myeloid leukemia (AML) is considered to have a good prognosis, relapse occurs in up to 40% of patients treated with chemotherapy
CD34+aldehyde dehydrogenase (ALDH)+‐H/Minimal residual disease (MRD)‐H patients had a significantly lower 2‐year relapse‐free survival (RFS) rate compared to CD34+ALDH+‐L and/or MRD‐L patients (33.3% [95% CI 4.6%‐67.6%] vs 90.3% [95% CI 64.2%‐97.7%], P < .0001, Figure 3C)
The results showed that CD34+ALDH+‐H/MRD‐H status was the only independent adverse prognostic factor for relapse (HR 27.5 [95% CI 3.1‐246.4], P = .0030)
Summary
T(8;21) acute myeloid leukemia (AML) is considered to have a good prognosis, relapse occurs in up to 40% of patients treated with chemotherapy. stratification is needed in order to guide appropriate treatment. Minimal residual disease (MRD) levels indicated by RUNX1‐ RUNX1T1 transcript levels as well as c‐KIT mutations have been demonstrated to be strong prognostic factors in t(8;21) AML.4-9 Their risk predictions are not perfect, and other markers have yet to be evaluated. CD34+CD38‐ is a putative immunophenotype of LSCs with the ability to generate leukemia in immunodeficient mice.11-13 This immunophenotype has been challenged because some studies have demonstrated that LSCs might exist in CD34+CD38+ and CD34‐ cells.. A clinical cohort study in intermediate and high cytogenetic risk AML showed that patients with a high percentage of ALDH + had adverse outcomes.. A clinical cohort study in intermediate and high cytogenetic risk AML showed that patients with a high percentage of ALDH + had adverse outcomes.24,26,27 This effect has not been evaluated in t(8;21) AML patients to date. We examined ALDH activity in 66 t(8;21) AML patients at diagnosis and evaluated its sole prognostic role and the impact of its combination with MRD on relapse
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