Interest of the XN-10® Analyzer to Screen for Myelodysplastic Syndromes on Complete Blood Count (CBC) Especially with Hemoglobin Levels and Neut-WX
Authors: Boutault Robin , Tremblais Sebastien , De Oliveira Lopes Mathilde , Peterlin Pierre , Le Bris Yannick , Godon Catherine , Theisen Olivier , Bene Marie C , Eveillard Marion 
Published: October 2019

Abstract
A prospective study was performed over one year at Nantes University Hospital in France, in order to investigate whether suspected myelodysplastic syndromes (MDS) could be detected on a complete blood count (CBC), the most rapid laboratory investigation. Indeed, the recently developed XN-10® (Sysmex, Kobe, Japan), provides novel CBC parameters witch could be useful to discriminate such patients from normal samples or from cytopenia of other etiology.
Seventy-nine patients were enrolled in the study, for whom a diagnosis of MDS was concluded based on CBC, bone marrow smears examination and karyotype. All patients were free of treatment, including transfusions, at inclusion. They were 40 men and 39 women with a median age of 77,9 years (range 36,4-92,4). CBC were performed on a Sysmex analyzer XN-10®, including investigation of reticulocytes and fluorimetric analysis of platelets. For comparison with normal values, results from 776 healthy samples, for which CBC were performed on the same analyzer and generated no flag, were used. All had parameters within the normal range according to age. The classical parameters of hemoglobin level, Mean Corpuscular Volume (MCV), reticulocytes, platelets and neutrophil counts were recorded. In addition, the extra-parameters, immature reticulocytes fraction (IRF%), platelets by fluorescence (PLT-F) and immature platelets fraction (IPF%), were taken into account. The neutrophils median position on the three axes as well as their dispersion (Neut-WX) were also measured by the analyser.
The primary end-point was to discriminate between MDS and healthy patients and the secondary end-point was to distinguish MDS with excess blasts, MDS with multilineage dysplasia and MDS with single lineage dysplasia within the MDS group and by comparison with controls. According to the WHO 2016 classification, 27 patients in the cohort had MDS with excess blasts, 26 MDS with multilineage dysplasia (among whom 7 had ring sideroblasts [RS], group 2), 16 MDS-RS and single lineage dysplasia, 7 MDS with single lineage dysplasia and 3 MDS with isolated del(5q). Forty-four patients had a normal karyotype and 28 displayed anomalies classically reported in MDS, including 5 complex karyotypes. Among the latter, 4 were associated with MDS with excess blasts.
Both classical and extra parameters indeed showed significant differences between the subgroups tested. Among the whole group of MDS patients, a number of parameters of all lineages were statistically different from the healthy cohort. The median level of hemoglobin was 9,8 g/dL (range 4,7-14,9), (p<0,0001), the median MCV 104,3 fL (range 75,4-123,9; p<0,0001), reticulocyte counts 44,3x109/L (range 8-165,9; p=0,041) and IRF% 16,7% (range 2,4-50,9; p<0,0001). An hemoglobin value below 11,5 g/dL was strongly suggestive of MDS with a sensitivity of 81% and specificity of 100%. The median platelet count was 164x109/L (range 8-505; p<0,0001) and median IPF% 8,8% (1,2-42; p<0,0001). Among leukocyte parameters, the MDS median neutrophil count was significantly lower at 2,15x109/L (range 0,17-13,67; p<0,001) and the Neut-WX value increased above 350. The latter, by itself, allowed to make a diagnosis of MDS with a sensitivity of 73,1% and a specificity of 96,9%.
When considering the three MDS subgroups of MDS with excess blasts, multilineage or single lineage dysplasia, although each of them was significantly different from controls for hemoglobin levels, MCV, IRF% and neutrophil counts (p<0,0001), they could not be discriminated by these parameters. In the subgroup of MDS with single lineage dysplasia, platelet counts were similar to those of controls, yet significantly higher than for MDS with excess blast or with multilineage dysplasia (p=0,004 and p=0,029 respectively).
Taken together, this study demonstrates that a simple CBC allows to screen for MDS using thresholds of 11,5 g/dL for hemoglobin and of 350 for Neut-WX. Blood smear examination should be performed in this situation even if the XN-10® analyzer does not raise an alarm, especially in unknown older patients.

Disclosures
No relevant conflicts of interest to declare.