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Introduction: The translocation t(8;21) is one of the most frequent chromosome translocations in AML. Molecular (cyto)genetics is regarded as the gold standard for diagnosis. However, due to the complicated variety of AML-related genetic abnormalities, comprehensive screening for all of these abnormalities may not be cost-effective. Therefore, a flow cytometric (FC) scoring system was generated in this study for rapid screening and diagnosis of t(8;21)AML., Methods: The immunophenotypic characteristics of leukemic cells and neutrophils in cases with t(8;21) AML or other subtypes of AML were analyzed to find a method for the flow diagnosis of t(8;21) AML., Results: In this study, we picked six FC features pointing to the diagnosis of t(8;21) AML: The blasts show high-intensity expression of CD34; aberrant expression of CD19, cCD79a, and CD56 in myeloblasts; co-expression of CD56 in neutrophils, especially in immature neutrophils; and a maturity disturbance in granulocytes. A six-point score was devised using these features. By ROC analysis, the AUC was 0.952, and the sensitivity, specificity, PPV, and NPV were 0.86, 0.90. 0.91, and 0.84 when the score was ≥3 points. The score was then prospectively validated on an independent cohort, and the AUC of the ROC curve for the validation cohort was 0.975. When the cutoff value was set at 3, the obtained sensitivity and specificity values were 0.91 and 0.94, respectively., Conclusions: The FC score described can be used for the identification and rapid screening of t(8;21) AML., (© 2018 John Wiley & Sons Ltd.)

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

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. [ABSTRACT FROM AUTHOR]

This review summarizes – with the practicing hematologist in mind – the methods used to determine measurable residual disease (MRD) in everyday practice with some future perspectives, and the current knowledge about the prognostic impact of MRD on outcome in acute myeloid leukemia (AML), excluding acute promyelocytic leukemia. Possible implications for choice of MRD method, timing of MRD monitoring, and guidance of therapy are discussed in general and in some detail for certain types of leukemia with specific molecular markers to monitor, including core binding factor (CBF)‐leukemias and NPM1‐mutated leukemias. [ABSTRACT FROM AUTHOR]