A comprehensive diagnostic approach combining Ogata score, flow cytometry, cytomorphological examination, and next-generation sequencing (NGS) may provide valuable insights into the diagnosis, prognosis, and risk stratification of myelodysplastic syndromes (MDS), according to a study recently published in Annals of Hematology.
“According to our findings, specific FC [flow cytometry] characteristics such as Ogata score and specific PAs [phenotypic aberrancies] correlate with mutational patterns, which can predict outcome and treatment response in the majority of patients. As a result, these low-cost first-line tools could help guide the selection of patients for mutational screening for optimal risk stratification,” the authors concluded.
The Ogata score demonstrated notable specificity (100%) and moderate sensitivity (59%) in the context of MDS diagnosis and prognostic assessment. The sensitivity improved to 83%, accompanied by a specificity of 87%, when at least 2 phenotypic aberrancies were detected in Ogata-negative patients.
The sensitivity of the Ogata score varied across MDS risk groups, with higher rates in lower-risk MDS (51%-47.5%) and robust sensitivity in higher-risk MDS (100%-78%).
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Furthermore, the study unveiled significant correlations between abnormal immunophenotypic features and genetic mutations. Positive Ogata scores (≥2) were linked to mutations in SRSF2, CD15 and U2AF1, CD56 and DNMT3A, and CD38 and TP53.
Multivariate analysis revealed that U2AF1 mutations were correlated with poorer overall survival, particularly when concomitant with del(20q) and/or chromosome 7 abnormalities. In addition, parameters such as Ogata score exceeding 2, along with specific flow cytometry and cytomorphological features, were significantly associated with inferior event-free survival.
Higher blast counts on flow cytometry analysis were correlated with specific flow cytometry aberrancies, Ogata scores of 2 or more, an increased risk of acute myeloid leukemia progression, shorter overall survival, and reduced event-free survival.
The application of NGS identified pathogenic or likely pathogenic mutations in 65.5% of patients. SF3B1, ASXL1, and TET2 emerged as the most frequently mutated genes. Moreover, the study found a strong correlation between high mutation counts and shorter overall survival and event-free survival.
Within the study cohort, CD34+ cells exhibited a median of 2 phenotype aberrations per patient, with the absence of CD33 expression being the most commonly detected abnormality (44% prevalence).
This retrospective study enrolled 106 patients with confirmed MDS diagnoses and 39 control subjects. Participants underwent immunophenotypic and cytogenetic tests, as well as cytomorphological examinations on bone marrow samples. Furthermore, NGS was performed on a subset of 58 cases.
Reference
Guarnera L, Fabiani E, Attrotto C, et al. Reliability of flow-cytometry in diagnosis and prognostic stratification of myelodysplastic syndromes: correlations with morphology and mutational profile. Ann Hematol. Published online August 3, 2023. doi:10.1007/s00277-023-05384-2
