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Myeloperoxidase in myelodysplastic syndromes
for healthy individuals and MDS cases, respectively (Online Supplementary Table S9). The mean inter-laboratory coefficient of variation point estimates ranged from 4.1% to 5.3% for healthy individuals and from 3.3% to 3.5% for MDS patients, depending on the setup procedures (Online Supplementary Table S9).
Discussion
To our knowledge, this is the first study to report on the diagnostic accuracy of neutrophil MPO expression meas- ured by flow cytometric analysis in PB to rule out MDS. Accordingly, a RCV value <30% identified patients at low risk of MDS in whom invasive BM aspirate could poten- tially be avoided. Because the 95%CI for both sensitivity (78-100%) and negative predictive value (83-100%) esti- mates were relatively imprecise, these findings warrant replication in a larger and more diverse cohort of patients.
Importantly, all ICUS patients had RCV values >30% and would be recommended for BM aspirate or biopsy, a strategy that complies with published guidelines.22,23 Although BM aspirate may help establish an alternate diagnosis for patients without MDS, it was not contribu- tive for any of 45 patients with unconfirmed suspicion of MDS in our prospective validation study. This observation may not be consistent with clinical practice and deserves
confirmation in an independent sample.
In contrast, flow cytometric analysis of neutrophil MPO
expression in PB had limited diagnostic value for ruling in MDS.28 Indeed, the specificity point estimates for a RCV value >30% ranged from 32% to 38% depending on the study sample, with positive predictive values varying between 31% and 59%. RCV values >38% achieved 100% specificity but at a cost of a 30% false-negative rate. Hence, the RCV of neutrophil MPO expression in PB would not add relevant information to cytomorphological evaluation of BM aspirate.
A thorough understanding of the changes in the RCV of neutrophil MPO expression in MDS patients was not within the scope of this study and requires further inves- tigation. However, we found that RCV values were elevat- ed across all MDS types. This observation might be explained by previous observations of hypogranulation in various MDS types12,13 and higher variability of neutrophil cell granularity in MDS clone29,30 as well as in extraclonal cells.31
Few studies have reported on the accuracy of flow cyto- metric analysis of alternate neutrophil antigen expression in PB for the diagnosis of MDS. Rashidi et al. reported decreased mean levels of CD10 expression in PB for high- grade MDS compared with cytopenic controls [2.2 (0.7) vs. 3.7 (0.7); P<0.001).9 However, this study failed to show a significant difference in levels of CD10 expression
AB
P<0.001
P<0.001 P=0.006
Figure 3. Area under the receiver operating characteristic curve for flow cytometric parameters of peripheral blood neutrophil myeloperoxidase expression in dis- criminating myelodysplastic syndromes (MDS). (A) Retrospective case control study. (B) Consecutive patients with suspected MDS. The area under the receiver oper- ating characteristic curve for each parameter was compared with that for the robust coefficient of variation (RCV). P-values were adjusted for multiple comparisons using the Bonferroni method. CI: Confidence Interval.
P=0.009
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