A Simple Complete Blood Count to Screen for Myelodysplastic Syndromes

Introduction

A diagnosis of myelodysplastic syndrome (MDS) is usually suspected upon the discovery of cytopenias (mostly anemia) at complete blood count (CBC). Yet, formal diagnosis requires complementary tests (morphology, bone marrow examination, karyotype, flow cytometry, molecular analyses) which are costly and time consuming. Here, a prospective study was performed over one year in order to investigate whether parameters from the XN-10® (Sysmex, Kobe, Japan) could reinforce a suspicion of MDS after a CBC. The primary end point was to discriminate MDS patients from normal samples and the secondary end-point was to to distinguish MDS with excess blasts (MDS-EB), MDS with multilineage dysplasia (MDS-MLD), MDS with single lineage dysplasia (MDS-SLD) and MDS with ring sideroblasts and single lineage dysplasia (MDS-RS-SLD) within the MDS group and by comparison with controls as described by the WHO 2016 classification.

Materials and Methods

One hundred and thirteen 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 63 men and 50 women with a median age of 82 years. CBC were performed on a Sysmex analyzer XN-10®, including classical parameters (hemoglobin level, Mean Corpuscular Volume (MCV), reticulocytes, platelets, neutrophils and extra-parameters i.e. platelets by fluorescence (PLT-F), brightly fluorescent immature platelets fraction (H-IPF%), immature reticulocytes fraction (IRF%) and the neutrophils median position on the three axes as well as their dispersion (Ne-WX). For comparison with normal values, results from 1083 subjects over 50 years old, for whom CBC were performed on the same analyzer, were used.. According to the WHO, 37 patients in the cohort had MDS-EB, 35 MDS-MDL (among whom 7 had ring sideroblasts [RS]), 26 MDS-SLD- RS, 12 MDS-SLD without RS and 3 MDS with isolated del(5q). Sixty-two patients had a normal karyotype, 24 displayed anomalies classically reported in MDS, and 8 had complex karyotypes. Among the latter, 7 were associated with MDS-EB.

Results

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 9.92+1.96 g/dL (p<0.0001), the median MCV (99.24+10.56 fL 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). The median platelet count was 194 +128 x10⁹/L (p<0.0001) and the median IPF% 8.8% (1.2-42; p<0.0001). Among leukocyte parameters, the MDS median neutrophil count was significantly lower at 3.08+2.58x10⁹/L (p<0,001) while Ne-WX was significantly higher (387+71; p<0,0001). The latter, by itself, allowed to predict a diagnosis of MDS with a sensitivity of 73.1% and a specificity of 96.9%. Considering patients over 50 years old, a combination of 4 parameters (Neut, Ne-WX, hemoglobin level and MCV) in a score allows to diagnose MDS with a sensitivity of 92% and a specificity of 81%. A suplementary score combining the last 4 parameters to 2 extra parameters (H-IPF and IRF) increased sensitivity and specificity at 94% both. When considering MDS subgroups (MDS-EB, multilineage or single lineage dysplasia and RS), although each of them was significantly different from controls for hemoglobin levels, MCV and IRF% and (p<0.0001), they could not be discriminated by these parameters. In the subgroup of MDS with single lineage dysplasia and ring sideroblasts, platelet counts were similar to those of controls, yet significantly higher than for MDS-EB or MDS-MLD (p=0.004 and p=0.029 respectively). Moreover, neutrophil counts were significantly lower in MDS-DML or MDS-EB than in MDS-SLD-RS.

Conclusion

This study demonstrates that a simple CBC allows to screen for MDS using a multiparameter score including Ne-WX. Blood smear examination should be performed in this situation even if the XN-10® analyzer does not raise any alarm, especially in unknown patients older than 50.