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      Implementation of the Ogata flow cytometric scoring system in routine diagnostics of myelodysplastic syndrome

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          Abstract

          Background and Aims

          Compiling evidence has emerged for the relevance of flow cytometric assessment as a valuable part of the diagnostic work‐up of myelodysplastic syndrome (MDS). This study aimed at evaluating the implementation of a simple flow cytometric scoring system (FCSS), the Ogata score, in a routine diagnostic laboratory.

          Methods

          A total of 35 patient samples with a clinical suspicion of MDS were retrospectively assessed using the FCSS. The accuracy of the FCSS was evaluated on the basis of the final diagnoses of the patients.

          Results

          The final diagnoses included 17 MDS, 4 other myeloid cancers, and 14 reactive changes. Thirty‐two of 35 (91%) were correctly scored by the FCSS. All 3 incorrect scores were from samples classified as “other myeloid cancers.” Of the initial pathological evaluation of the bone marrows, 20% were inconclusive or incorrect. All inconclusive samples were correctly scored using the FCSS.

          Conclusion

          The FCSS evaluated here has high accuracy and low complexity. Cases with inconclusive pathological evaluation will especially potentially benefit from adding the Ogata score to the diagnostic work‐up. The system will be feasible to implement in most flow cytometry laboratories without the need for supplemental antibody panels. It should be emphasized that the FCSS, in our hands, provided poor discrimination between MDS and other myeloid clonal diseases.

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          Most cited references17

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          Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation.

          Marrow cells of myeloid lineage from 115 patients with myelodysplastic syndrome (MDS) were characterized by multidimensional flow cytometry and compared with findings in 104 patients with various disorders and 25 healthy donors. Based on phenotypic and scatter characteristics, a flow cytometric scoring system (FCSS) was developed that allowed for a simple numerical display of results. The flow cytometric scores were categorized as normal/mild (0-1), moderate (2-3), or severe (> or = 4). Most flow cytometric abnormalities were significantly (P <.05) more frequent in patients with MDS than in the control cohort. Flow cytometric scores in MDS patients were then retrospectively compared with marrow blast counts assessed by morphology, cytogenetics, hematologic parameters, and International Prognostic Scoring System (IPSS) risk categorization. The flow cytometric scores correlated inversely with leukocyte and absolute neutrophil counts (P <.01) and correlated directly with IPSS scores (P <.01) and with IPSS cytogenetic risk categories (P <.01). In 111 MDS patients who underwent allogeneic hematopoietic stem cell transplantation, flow scores correlated with posttransplantation outcome. The probabilities of posttransplantation relapse were 3%, 15%, and 33% for patients with mild, moderate, and severe FCSS scores, respectively (P <.01), and overall survival was 74%, 40%, and 36%, respectively, for the 3 groups (P <.01). In multivariate analyses, there was a significant contribution of the flow score independent of the IPSS in predicting survival and relapse (P <.01, P =.02, and P =.03, respectively). These data suggest that FCSS is useful in assessing marrows for diagnosis of MDS and in determining the prognostic outcome in patients with this disorder.
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            Myelodysplastic syndromes: 2015 Update on diagnosis, risk-stratification and management.

            The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy.
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              Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study.

              The current World Health Organization classification of myelodysplastic syndromes is based morphological evaluation of bone marrow dysplasia. In clinical practice, the reproducibility of the recognition of dysplasia is usually poor especially in cases that lack specific markers such as ring sideroblasts and clonal cytogenetic abnormalities. We aimed to develop and validate a flow cytometric score for the diagnosis of myelodysplastic syndrome. Four reproducible parameters were analyzed: CD34(+) myeloblast-related and B-progenitor-related cluster size (defined by CD45 expression and side scatter characteristics CD34(+) marrow cells), myeloblast CD45 expression and granulocyte side scatter value. The study comprised a "learning cohort" (n=538) to define the score and a "validation cohort" (n=259) to confirm its diagnostic value. With respect to non-clonal cytopenias, patients with myelodysplastic syndrome had increased myeloblast-related cluster size, decreased B-progenitor-related cluster size, aberrant CD45 expression and reduced granulocyte side scatter (P<0.001). To define the flow cytometric score, these four parameters were combined in a regression model and the weight for each variable was estimated based on coefficients from that model. In the learning cohort a correct diagnosis of myelodysplastic syndrome was formulated in 198/281 cases (sensitivity 70%), while 18 false-positive results were noted among 257 controls (specificity 93%). Sixty-five percent of patients without specific markers of dysplasia (ring sideroblasts and clonal cytogenetic abnormalities) were correctly classified. A high value of the flow cytometric score was associated with multilineage dysplasia (P=0.001), transfusion dependency (P=0.02), and poor-risk cytogenetics (P=0.04). The sensitivity and specificity in the validation cohort (69% and 92%, respectively) were comparable to those in the learning cohort. The likelihood ratio of the flow cytometric score was 10. A flow cytometric score may help to establish the diagnosis of myelodysplastic syndrome, especially when morphology and cytogenetics are indeterminate.
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                Author and article information

                Contributors
                samm@regionsjaelland.dk
                Journal
                Health Sci Rep
                Health Sci Rep
                10.1002/(ISSN)2398-8835
                HSR2
                Health Science Reports
                John Wiley and Sons Inc. (Hoboken )
                2398-8835
                26 September 2018
                November 2018
                : 1
                : 11 ( doiID: 10.1002/hsr2.v1.11 )
                : e90
                Affiliations
                [ 1 ] Department of Clinical Biochemistry Zealand University Hospital Roskilde Denmark
                [ 2 ] Department of Haematology Zealand University Hospital Roskilde Denmark
                [ 3 ] Department of Haematology Odense University Hospital Odense Denmark
                [ 4 ] Department of Clinical Pathology Zealand University Hospital Roskilde Denmark
                [ 5 ] Department of Pathology, Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
                Author notes
                [*] [* ] Correspondence

                Sara Maj Hyldig Matzen, Department of Clinical Biochemistry, Zealand University Hospital, Sygehusvej 10, DK‐4000 Roskilde, Denmark.

                Email: samm@ 123456regionsjaelland.dk

                Author information
                http://orcid.org/0000-0003-4213-3672
                Article
                HSR290 HSR-2018-02-0052.R2
                10.1002/hsr2.90
                6242364
                30623045
                686051b0-5f13-4767-8c24-e25658ac6995
                © 2018 The Authors. Health Science Reports published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 February 2018
                : 12 July 2018
                : 09 August 2018
                Page count
                Figures: 2, Tables: 1, Pages: 6, Words: 3167
                Categories
                Hematology
                Pathology
                Research Article
                Research Articles
                Custom metadata
                2.0
                hsr290
                November 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.3 mode:remove_FC converted:20.11.2018

                cd34,fcss,flow cytometry,mds,pitfalls
                cd34, fcss, flow cytometry, mds, pitfalls

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