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      Improving the differential diagnosis between myelodysplastic syndromes and reactive peripheral cytopenias by multiparametric flow cytometry: the role of B-cell precursors

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          Abstract

          Background

          Immunophenotyping is a valuable ancillary technique for the differential diagnosis between myelodysplastic syndromes (MDS) with low bone marrow (BM) blast counts and a normal karyotype, and reactive peripheral (PB) cytopenias. Our aim was to search for the most important variables for this purpose. We also analyzed the age variation of BM B-cell precursors (BCP) and its differences in reactive and clonal cytopenias.

          Methods

          Immunophenotypic analyzes were performed in BM of 54 patients with MDS (76% with BM blasts <5%) and 35 cases of reactive cytopenias. Healthy allogeneic BM transplantation donors (n = 41) were used as controls. We used a four-color panel of antibodies analyzing 9 granulocytic, 8 monocytic and 6 CD34 + cell features.

          Results

          Asynchronous shift to the left in maturing granulocytes and increase in CD16 + monocytes were also found in reactive PB cytopenias, but the most important aberrancies in MDS were seen in myeloid CD34 + cells. Decrease in BCP, that is a hallmark of MDS, could also be found in reactive cytopenias, especially in patients >55 years. % BM BCP could be calculated by the formula: (−7.97 × log age) + (4.24 × log % CD34 + cells) – (0.22 x nr. alterations CD34 + cells) + 0.577. Corrected R 2 = 0.467.

          Conclusion

          Analysis of myelomonocytic precursors and CD34 + cells was satisfactory for the differential diagnosis between reactive PB cytopenias and MDS. The most specific alterations were found in CD34 + cells. Comparison of the values obtained with those of normal age-matched controls is recommended.

          Virtual slides

          The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1975931809154663

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          Most cited references37

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          Revised international prognostic scoring system for myelodysplastic syndromes.

          The International Prognostic Scoring System (IPSS) is an important standard for assessing prognosis of primary untreated adult patients with myelodysplastic syndromes (MDS). To refine the IPSS, MDS patient databases from international institutions were coalesced to assemble a much larger combined database (Revised-IPSS [IPSS-R], n = 7012, IPSS, n = 816) for analysis. Multiple statistically weighted clinical features were used to generate a prognostic categorization model. Bone marrow cytogenetics, marrow blast percentage, and cytopenias remained the basis of the new system. Novel components of the current analysis included: 5 rather than 3 cytogenetic prognostic subgroups with specific and new classifications of a number of less common cytogenetic subsets, splitting the low marrow blast percentage value, and depth of cytopenias. This model defined 5 rather than the 4 major prognostic categories that are present in the IPSS. Patient age, performance status, serum ferritin, and lactate dehydrogenase were significant additive features for survival but not for acute myeloid leukemia transformation. This system comprehensively integrated the numerous known clinical features into a method analyzing MDS patient prognosis more precisely than the initial IPSS. As such, this IPSS-R should prove beneficial for predicting the clinical outcomes of untreated MDS patients and aiding design and analysis of clinical trials in this disease.
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            New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge.

            The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the International Prognostic Scoring System (IPSS) in 1997, knowledge concerning the prognostic impact of abnormalities has increased substantially. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 2,902 patients. Patients were included from the German-Austrian MDS Study Group (n = 1,193), the International MDS Risk Analysis Workshop (n = 816), the Spanish Hematological Cytogenetics Working Group (n = 849), and the International Working Group on MDS Cytogenetics (n = 44) databases. Patients with primary MDS and oligoblastic acute myeloid leukemia (AML) after MDS treated with supportive care only were evaluated for overall survival (OS) and AML evolution. Internal validation by bootstrap analysis and external validation in an independent patient cohort were performed to confirm the results. In total, 19 cytogenetic categories were defined, providing clear prognostic classification in 91% of all patients. The abnormalities were classified into five prognostic subgroups (P < .001): very good (median OS, 61 months; hazard ratio [HR], 0.5; n = 81); good (49 months; HR, 1.0 [reference category]; n = 1,809); intermediate (26 months; HR, 1.6; n = 529); poor (16 months; HR, 2.6; n = 148); and very poor (6 months; HR, 4.2; n = 187). The internal and external validations confirmed the results of the score. In conclusion, these data should contribute to the ongoing efforts to update the IPSS by refining the cytogenetic risk categories.
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              Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: Consensus statements and report from a working conference.

              The classification, scoring systems, and response criteria for myelodysplastic syndromes (MDS) have recently been updated and have become widely accepted. In addition, several new effective targeted drugs for patients with MDS have been developed. The current article provides a summary of updated and newly proposed markers, criteria, and standards in MDS, with special reference to the diagnostic interface and refinements in evaluations and scoring. Concerning the diagnostic interface, minimal diagnostic criteria for MDS are proposed, and for patients with unexplained cytopenia who do not fulfill these criteria, the term 'idiopathic cytopenia of uncertain significance' (ICUS) is suggested. In addition, new diagnostic and prognostic parameters, histopathologic and immunologic determinants, proposed refinements in scoring systems, and new therapeutic approaches are discussed. Respective algorithms and recommendations should facilitate diagnostic and prognostic evaluations in MDS, selection of patients for therapies, and the conduct of clinical trials.
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                Author and article information

                Contributors
                suireis@unicamp.br
                ftraina@fmrp.usp.br
                kmetze@fcm.unicamp.br
                ilmetze@unicamp.br
                Journal
                Diagn Pathol
                Diagn Pathol
                Diagnostic Pathology
                BioMed Central (London )
                1746-1596
                29 April 2015
                29 April 2015
                2015
                : 10
                : 44
                Affiliations
                [ ]Hematology and Hemotherapy Center, University of Campinas, Carlos Chagas Street, 480, 13083-878 Campinas, São Paulo, Brazil
                [ ]Faculty of Medicine of Ribeirão Preto, University of São Paulo, Vila Monte Alegre, 14048-900, Ribeirão Preto, Sao Paulo, Brazil
                [ ]Faculty of Medicine, University of Campinas, Tessália Vieira de Camargo Street 126, 13083-887, Campinas, São Paulo, Brazil
                Article
                259
                10.1186/s13000-015-0259-3
                4428240
                25924846
                a112bdb8-02c6-4a27-9616-b53898e3b77c
                © Reis-Alves et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 December 2014
                : 31 March 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Pathology
                mds,flow cytometry,cd34+ cells,b-cell precursors,diagnosis
                Pathology
                mds, flow cytometry, cd34+ cells, b-cell precursors, diagnosis

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