A flow cytometric score (FCM-score) developed in 2012,, which uses 4 parameters to distinguish low-grade myelodysplastic syndromes (MDS) from nonclonal cytopenias,, is simple and practical for screening patients with MDS, according to research published in The American Journal of Translational Medicine.
To improve upon this method, researchers investigated a gating strategy and cluster of differentiation (CD) markers in FCM for an MDS diagnosis. Compared with the original score, the new version (MFCM-score) exhibited better accuracy, objectiveness, and clinical application.
MDS, classified by the World Health Organization (WHO) as myeloid neoplasms, comprises a group of heterogeneous diseases characterized by ineffective hematopoiesis, peripheral blood cytopenias, and dysplasia in 1 or more myeloid lineage cells in bone marrow, the authors explained.
Although the WHO classifies MDS based on peripheral cytopenias and bone marrow dysplasia evaluations, in clinical practice, patients may be negative for these diagnostic markers yet still have MDS, warranting additional diagnostic measure for these patients.
Because research has shown flow cytometry is capable of diagnosing reactive and clonal proliferations of bone marrow hematopoietic cells, the method has been explored as a potential diagnostic tool for MDS. However, because flow cytometry is expensive and requires a large number of antibodies, it is untenable in developing countries. To overcome these issues, an FCM-score was developed in 2012.
In the current study, the researchers recruited participants from a single hospital in China. Based on their medical history, clinical characteristics, morphological changes, and response to treatment, the patients were divided into MDS (n = 54) and nonclonal cytopenias (non-MDS; n = 40) cohorts.
Clinical and demographic data, in addition to bone marrow samples, were collected. Under the original method for FMC-scoring, combinations of antibodies CD34, CD19, CD33, and CD45 are analyzed for the following parameters: myeloblast-related cluster size (myeloblast-related cells/all nucleated cells), B-progenitor–related cluster size (B–progenitor-related cells/all CD34+ cells), CD45 mean fluorescence intensity ratio (lymphocytes/myeloid blast cells), and side scatter (SSC) peak channel ratio (granulocyte/lymphocyte). Originally, a value of 1 was assigned to each parameter and MDS diagnosed if the FCM-score was ≥ 2, the authors explained.
The original FCM-score also used low SSC and CD45 expression to separate B lymphocyte progenitor cells and myeloblasts. In contrast, the researchers’ gating and CD strategy “used CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34+CD45dimm population."
Using patients’ data, the the investigators compared the 2 scores (at the cutoff of 2) and analyzed the relationship between the MFCM-score and the Revised International Prognostic Scoring System (IPSS-R) for MDS.
Analyses revealed:
- Using the FCM-score, 49 of 54 MDS cases were diagnosed (sensitivity 90.7%); 7 false-positives (misdiagnosed) were found in non-MDS patients (specificity 82.5%); the agreement between clinical and FCM-score diagnosis was 87.2%; the positive predictive value (PPV) and negative predictive values (NPV) were 87.5% and 86.8%, respectively
- Using the MFCM-score, 52 of 54 MDS cases were correctly diagnosed (sensitivity 96.3%); there were 5 false-positives in the non-MDS cohort (specificity 87.5%); the agreement between clinical and FCM-score diagnosis was 92.6%; the PPV and NPV were 91.2% and 94.6%, respectively
- Chi square tests showed that the diagnostic rates by MFCM-score and FCM-score were similar (P > 0.05)
- MFCM-score had a positive correlation with the IPSS-R prognosis classification for MDS (Spearman r = 0.848; P < .001)
- All parameters in the MFCM-score were positively correlated to the IPSS-R grades in MDS (P < .01)
The relatively small sample size and short period of follow-up mark limitations to the study, and the MFCM-score should be validated in large, multicenter prospective studies, the authors wrote.
“We can follow up the treatment and survival of MDS patients to validate the clinical significance of the MFCM-score in the treatment and prognosis of patients,” the researchers concluded. “The MFCM-score covers not only low-grade MDS, but also all MDS subtypes, and it also has prognostic value for survival and can be used for treatment tracking.”
Reference
Guo J, Wang H, Xiong S, et al. Simplified flow cytometry scoring for diagnosis and prognosis of myelodysplastic symptom. Am J Transl Res. 2020; 12(11):7449-7458.
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