Implementation of erythroid lineage analysis by flow cytometry in diagnostic models for myelodysplastic syndromes

Abstract

Flow cytometric analysis is a recommended tool in the diagnosis of myelodysplastic syndromes. Current flow cytometric approaches evaluate the (im)mature myelo-/monocytic lineage with a median sensitivity and specificity of ~71% and ~93%, respectively. We hypothesized that the addition of erythroid lineage analysis could increase the sensitivity of flow cytometry. Hereto, we validated the analysis of erythroid lineage parameters recommended by the International/European LeukemiaNet Working Group for Flow Cytometry in Myelodysplastic Syndromes, and incorporated this evaluation in currently applied flow cytometric models. One hundred and sixty-seven bone marrow aspirates were analyzed; 106 patients with myelodysplastic syndromes, and 61 cytopenic controls. There was a strong correlation between presence of erythroid aberrancies assessed by flow cytometry and the diagnosis of myelodysplastic syndromes when validating the previously described erythroid evaluation. Furthermore, addition of erythroid aberrancies to two different flow cytometric models led to an increased sensitivity in detecting myelodysplastic syndromes: from 74% to 86% for the addition to the diagnostic score designed by Ogata and colleagues, and from 69% to 80% for the addition to the integrated flow cytometric score for myelodysplastic syndromes, designed by our group. In both models the specificity was unaffected. The high sensitivity and specificity of flow cytometry in the detection of myelodysplastic syndromes illustrates the important value of flow cytometry in a standardized diagnostic approach. The trial is registered at www.trialregister.nl as NTR1825; EudraCT n.: 2008-002195-10.

Figure 1.

MDS-FC results in the MDS and control group. The diagnostic score and the integrated MDS-FC score in patients within the MDS group and control group. The arrows demonstrate the patients changing groups after addition of erythroid evaluation as recommended by the IMDS-flow group. *Flow cytometric results showed minimal dysplastic features, not enough for MDS.

Figure 2.

WHO-classifications within different MDS-FC groups. Distribution of WHO-classifications within the original iFS categories, and iFS categories after the addition of erythroid evaluation. With the addition of the erythroid compartment, patients shift into a higher MDS-FC category. Category A ‘no MDS-related features’, B ‘limited number of changes associated with MDS’, or C ‘features consistent with MDS’. Absolute patient numbers are provided in the Online Supplementary Files (Table S2)