Peripheral blood MDS score: A new flow cytometric tool for the diagnosis of myelodysplastic syndromes

Background: Myelodysplastic syndromes (MOS) are a heterogeneous group of hematopoietic disorders diagnosed using morphologic and clinical findings supported by cytogenetics. Because abnormalities may be subtle, diagnosis using these approaches can be challenging. Flow cytometric (FCM) approaches have been described; however the value of bone marrow immunophenotyping in MOS remains unclear due to the variability in detected abnormalities. We sought to refine the FCM approach by using peripheral blood (PB) to create a clinically useful tool for the diagnosis of MOS. Methods: PB from 15 patients with MOS was analyzed by multiparametric flow cytometry using an extensive panel of monoclonal antibodies. Patterns of neutrophil antigen expression were compared with those of normal controls (n = 16) to establish light scatter and/or immunophenotypic abnormalities that correlated with MOS. A scoring algorithm was developed and validated prospectively on a blinded patient set. Results: PB neutrophils from patients with MOS had lower side scatter and higher expression of CD66 and CD1 1a than did controls. Some MOS PB neutrophils demonstrated abnormal CD1 16 and CD10 expression. Because none of these abnormalities proved consistently diagnostic, we sought to increase the power of the assay by devising a scoring system to allow the association of multiple abnormalities and account for phenotypic variations. The PB MOS score differentiated patients with MOS from controls (P < 0.0001) in the test set. In a prospective validation, the PB MOS score successfully identified patients with MOS (sensitivity 73%, specificity 90%). Conclusions: FCM analysis of side scatter and only four additional immunophenotypic parameters of PB neutrophils using the PB MOS score proved more sensitive than standard laboratory approaches and may provide an additional, more reliable diagnostic tool in the identification of MOS. (C) 2005 Wiley-Liss, Inc.