title: Identification of distinct prognostic subgroups in low- and intermediate-1-risk myelodysplastic syndromes by flow cytometry.
abstract: The World Health Organization (WHO) classification contributes to refined classification and prognostication of myelodysplastic syndromes (MDSs). Flow cytometry might add significantly to diagnostic and prognostic criteria. Our analysis of bone marrow samples from 50 patients with MDS showed aberrant expression of differentiation antigens in the myelomonocytic lineage. This also accounted for refractory anemia (RA) with or without ringed sideroblasts (RS), indicating multilineage dysplasia. In 38% of patients, CD34(+) myeloid blasts expressed CD5, CD7, or CD56. Flow cytometry data were translated into a numerical MDS flow-score. Flow-scores increased significantly from RA with or without RS, refractory cytopenia with multilineage dysplasia (RCMD) with or without RS up to refractory anemia with excess of blasts-1 (RAEB-1) and RAEB-2. No significant differences were observed between WHO cytogenetic subgroups. Flow-scores were highly heterogeneous within International Prognostic Scoring System (IPSS) subgroups. Patients in progression to advanced MDS or acute myeloid leukemia had a significantly higher flow-score compared with non-transfusion-dependent patients. In 60% of patients with transfusion dependency or progressive disease, myeloid blasts expressed CD7 or CD56, in contrast to only 9% of non-transfusion-dependent patients. Moreover, all patients with pure RA with or without RS with aberrant myeloid blasts showed an adverse clinical course. In conclusion, flow cytometry in MDS identified aberrancies in the myelomonocytic lineage not otherwise determined by cytomorphology. In addition, flow cytometry identified patients at risk for transfusion dependency and/or progressive disease independent of known risk groups, which might have impact on treatment decisions and the prognostic scoring system in the near future.
authors.affiliation: Department of Hematology, Vrije Universiteit (VU) University Medical Center, VU-Institute for Cancer and Immunology, Amsterdam, The Netherlands. a.vandeloosdrecht@vumc.nl
authors.forename: Arjan A
authors.initials: AA
authors.lastname: van de Loosdrecht
authors.forename: Theresia M
authors.initials: TM
authors.lastname: Westers
authors.forename: August H
authors.initials: AH
authors.lastname: Westra
authors.forename: Angelika M
authors.initials: AM
authors.lastname: Dräger
authors.forename: Vincent H J
authors.initials: VH
authors.lastname: van der Velden
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D018450:Disease Progression; D005434:Flow Cytometry / Q000379:methods*; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D054503:Lymphoid Progenitor Cells / Q000276:immunology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000145:classification* / Q000175:diagnosis* / Q000276:immunology; D023461:Myeloid Progenitor Cells / Q000276:immunology; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014944:World Health Organization
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor