ELN Scoring System Shows Similar Accuracy to iFS for MDS Diagnosis

A new validation study affirms the value of flow cytometry to diagnose myelodysplastic neoplasms in cytopenic patients. It also found that a newly developed scoring system has similar diagnostic accuracy to a more established, but also more elaborate, system. ¹

The findings, which were published in the journal HemaSphere, could offer clinicians an easier way to get to a definitive diagnosis, even in patients with low-risk myelodysplastic syndrome (MDS).

A newly developed MDS scoring system has similar diagnostic accuracy to a more established, but also more elaborate, system, a new study found. | Image credit: syahrir - stock.adobe.com

Several methods of using flow cytometry to evaluate bone marrow have been developed for MDS, and the tool is supported by the World Health Organization, noted corresponding author Arjan A. van de Loosdrecht, MD, PhD, of Amsterdam University Medical Center, and colleagues. Two of the most established systems are the 4-parameter Ogata Score and the 44-parameter Integrated Flow Score (iFS), they noted.

Yet, while flow cytometry as a diagnostic tool is well-established, there remains a lack of consensus about which scoring system is optimal, the authors explained. That lack of clarity, they cautioned, may limit the widespread clinical use of such tools.

In response, the European LeukemiaNet/International Myelodysplastic Syndrome Flow Cytometry Working Group (ELN-iMDS) conducted a study that resulted in the identification of 17 immunophenotypic core markers that can be used to identify MDS and/or chronic myelomonocytic leukemia (CMML).²

In that study, the authors found that using a cut-off of 3 immunophenotypic marker aberrancies had 80% concordance with cytomorphology, and a cut-off of >3% myeloid progenitor cells had a positive predictive value of 98%. Those parameters became the ELN Scoring System.

In the new study, the investigators recruited 180 people with MDS and 54 pathological controls in order to validate the ELN system. Most of the patients with MDS (76%) were low risk because they had bone marrow blast percentages below 5%, and 62% fell into the very low, low, or moderate-low risk categories using the International Prognostic Scoring System-Molecular.

Flow cytometry showed that patients in the MDS group had a median of 5 aberrancies, compared with 2 aberrancies in the control group. The authors found that their cutoff of 3 or more aberrant markers led to 87% diagnostic accuracy comparable to an integrated diagnostic approach. The iFS showed 91% accuracy, and the Ogata Score had an accuracy of 71% (P < 0.001). The sensitivity of the ELN system was similar to that of the iFS and superior to that of the Ogata Score.

Turning to patients with low-risk MDS, the investigators found both the iFS and ELN systems had sensitivities of 87%, while the Ogata Score had a sensitivity of just 54%. All 3 scoring systems performed with high sensitivity in high-risk patients.

“The ELN Scoring System was superior to the Ogata Score and had, despite significantly fewer parameters, a minimal loss of diagnostic accuracy compared to the iFS,” the authors concluded.

Yet, the investigators also noted that the ELN system has limitations. Eighteen patients with MDS were falsely categorized as negative cases. The iFS system would have caught most of those cases, labeling 8 of those 18 patients as having symptoms “consistent with MDS,” and 7 of the patients as having “limited signs of dysplasia.”

The ELN system also incorrectly categorized 13 of the 52 control patients as having MDS, a false positivity rate of 24%. Applying Ogata scores to those 13 patients resulted in 10 patients being correctly labeled as negative, and while the iFS would have flagged 9 of the 13 patients as showing limited signs of dysplasia, only 3 of the 13 would have been categorized as positive for MDS, van de Loosdrecht and colleagues noted.

The reason, they suspect, is that the ELN system counts marker aberrancies without regard to their cell subset, while the iFS requires at least 2 aberrancies in at least 2 separate cell subsets to generate a positive diagnosis. Thus, a patient with multiple dysplastic features concentrated in a single subset, or patients with single dysplastic features in multiple subsets would be classified as positive using the ELN system but negative using iFS.

“Furthermore, we showed that CMML-specific markers contributed to false-positivity; removing these markers improved specificity, yet not the overall accuracy,” the investigators wrote.

The investigators noted it is important the flow cytometry not be seen as a standalone tool but rather as a valuable tool in a wider, integrated diagnostic approach. Their data show the ELN Scoring System can help advance the use of flow cytometry.

“Its simplicity in combination with the extensive recommendations published should allow easy and broad implementation in laboratories,” they concluded.

References

1. Veenstra CR, Alhan C, Westers TM, van de Loosdrecht AA. Validation of the diagnostic potential of 17 immunophenotypic core markers defined by the ELN-iMDS-Flow Working Group in an independent cohort of patients with MDS. Hemasphere. 2025;9(3):e70075. doi:10.1002/hem3.70075
2. Kern W, Westers TM, Bellos F, et al. Multicenter prospective evaluation of diagnostic potential of flow cytometric aberrancies in myelodysplastic syndromes by the ELN iMDS flow working group. Cytometry B Clin Cytom. 2023;104(1):51-65. doi:10.1002/cyto.b.22105