A threshold of 10% for myeloperoxidase by flow cytometry is valid to classify acute leukemia of ambiguous and myeloid origin

Abstract

Results: Cell lineage-defining markers and SBB staining were analyzed retrospectively in a cohort of 198 patients who presented with acute leukemia. Eight patients were positive for SBB (>3%), but were considered negative for cMPO (<10%); six patients were negative for SBB ( 3%) and positive for cMPO (!10%) staining. In six patients, we found 10-20% cMPO positive leukemic cells. Five of these cases were SBB positive; the sixth patient showed a clear myeloid phenotype without positivity of any lymphoid marker. Using a 10% cut-off instead of 20% would have changed diagnosis from ALL into MPAL in two patients; both cases were SBB positive by morphology.Conclusion: We conclude that a 10% cut-off is a secure lower limit for cMPO expression and can be used independently from SBB expression. V C 2013 International Clinical Cytometry Society

Acute Leukemias of Ambiguous Origin

“…35,36 A threshold of 10% expression has been used by the EGIL group. 3 However, discordant cases are found when both methods are compared, 6,37 leading to the conclusion that the 10% threshold may be conservative but not very sensitive. It should be emphasized that MPO expression can be a difficult test to establish by FCM immunophenotypic analysis since differences in permeabilization reagents and various antibodies have been reported.…”

“…MPO stands as the most robust marker that will identify myeloid engagement. Recent publications have redefined the threshold for MPO positivity, 5,6 and yet most MPAL cases with a myeloid component will express MPO broadly in most blasts. An alternative, for MPAL with a strong monocytic differentiation, is represented by (very rare) cases in which blasts will be positive for nonspecific esterase and/or express at least two of the following antigens: CD14, CD11c, CD36, CD64, or cytoplasmic lysozyme.…”

How I treat mixed-phenotype acute leukemia

“…Myeloid origin can be determined with a set of monocytic markers, or more commonly by MPO expression. Although various thresholds for flowbased MPO positivity were introduced over the years (eg, 10% of blast population 1,5 ), no specific threshold has been acknowledged in the 2008 WHO monograph. 3,6 Compared with the EGIL classification, the 2008 WHO classification uses a more limited set of lineage markers that can be more consistently applied.…”

Lineage determination in mixed phenotype acute leukemia

“…3 In our practice, we do not adopt a 10% or higher cutoff of MPO expression by flow cytometry, as suggested in the recent paper mentioned in your letter. 4 Rather, we comprehensively analyze the immunophenotypic deviations in conjunction with MPO expression when determining the extent of myeloid differentiation. In this case, while only 3% of neoplastic blasts express MPO, in conjunction with the other myeloid antigen expression, including CD13, CD15, CD33 and CD117, there is sufficient myeloid differentiation for a diagnosis of MPAL, T/myeloid.…”