Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group
Theresia M. Westers,
Eline M.P. Cremers,
Uta Oelschlaegel,
Ulrika Johansson,
Peter Bettelheim,
Sergio Matarraz,
Alberto Orfao,
Bijan Moshaver,
Lisa Eidenschink Brodersen,
Michael R. Loken,
Denise A. Wells,
Dolores Subirá,
Matthew Cullen,
Jeroen G. te Marvelde,
Vincent H.J. van der Velden,
Frank W.M.B. Preijers,
Sung-Chao Chu,
Jean Feuillard,
Estelle Guérin,
Katherina Psarra,
Anna Porwit,
Leonie Saft,
Robin Ireland,
Timothy Milne,
Marie C. Béné,
Birgit I. Witte,
Matteo G. Della Porta,
Wolfgang Kern,
Arjan A. van de Loosdrecht
Affiliations
Theresia M. Westers
Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, The Netherlands
Eline M.P. Cremers
Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, The Netherlands
Uta Oelschlaegel
Department of Internal Medicine, Universitätsklinikum “Carl-Gustav-Carus”, Dresden, Germany
Ulrika Johansson
Department of Haematology, University Hospitals NHS Foundation Trust, Bristol, UK
Peter Bettelheim
First Medical Department, Elisabethinen Hospital, Linz, Austria
Sergio Matarraz
Servicio Central de Citometría (NUCLEUS) and Department of Medicine, Centro de Investigación del Cáncer, Instituto de Biologia Celular y Molecular del Cáncer, (CSIC/USAL and IBSAL), Universidad de Salamanca, Spain
Alberto Orfao
Servicio Central de Citometría (NUCLEUS) and Department of Medicine, Centro de Investigación del Cáncer, Instituto de Biologia Celular y Molecular del Cáncer, (CSIC/USAL and IBSAL), Universidad de Salamanca, Spain
Bijan Moshaver
Isala Clinics, Zwolle, The Netherlands
Lisa Eidenschink Brodersen
HematoLogics, Inc., Seattle, WA, USA
Michael R. Loken
HematoLogics, Inc., Seattle, WA, USA
Denise A. Wells
HematoLogics, Inc., Seattle, WA, USA
Dolores Subirá
Department of Hematology, Hospital Universitario de Guadalajara, Spain
Matthew Cullen
HMDS, St. James’s University Hospital, Leeds, UK
Jeroen G. te Marvelde
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
Vincent H.J. van der Velden
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands
Frank W.M.B. Preijers
Department of Laboratory Medicine – Laboratory for Hematology, Radboud University Medical Center, Nijmegen, The Netherlands
Sung-Chao Chu
Department of Hematology and Oncology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan
Jean Feuillard
Laboratoire d’Hématologie, CHU Dupuytren, Limoges, France
Estelle Guérin
Laboratoire d’Hématologie, CHU Dupuytren, Limoges, France
Katherina Psarra
Department of Immunology-Histocompatibility, Evangelismos Hospital, Athens, Greece
Anna Porwit
Department of Pathobiology and Laboratory Medicine, University of Toronto, University Health Network, Toronto General Hospital, ON, Canada;Department of Pathology, Karolinska University Hospital, Stockholm, Sweden
Leonie Saft
Department of Pathology, Karolinska University Hospital, Stockholm, Sweden
Robin Ireland
King’s College Hospital, London, UK
Timothy Milne
King’s College Hospital, London, UK
Marie C. Béné
Laboratoire d’Hématologie, CHU de Nantes, France
Birgit I. Witte
Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
Matteo G. Della Porta
Department of Hematology and Oncology, Fondazione IRCCS Policlinico San Matteo, and University of Pavia, Italy
Wolfgang Kern
MLL Munich Leukemia Laboratory, Germany
Arjan A. van de Loosdrecht
Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, The Netherlands
Current recommendations for diagnosing myelodysplastic syndromes endorse flow cytometry as an informative tool. Most flow cytometry protocols focus on the analysis of progenitor cells and the evaluation of the maturing myelomonocytic lineage. However, one of the most frequently observed features of myelodysplastic syndromes is anemia, which may be associated with dyserythropoiesis. Therefore, analysis of changes in flow cytometry features of nucleated erythroid cells may complement current flow cytometry tools. The multicenter study within the IMDSFlow Working Group, reported herein, focused on defining flow cytometry parameters that enable discrimination of dyserythropoiesis associated with myelodysplastic syndromes from non-clonal cytopenias. Data from a learning cohort were compared between myelodysplasia and controls, and results were validated in a separate cohort. The learning cohort comprised 245 myelodysplasia cases, 290 pathological, and 142 normal controls; the validation cohort comprised 129 myelodysplasia cases, 153 pathological, and 49 normal controls. Multivariate logistic regression analysis performed in the learning cohort revealed that analysis of expression of CD36 and CD71 (expressed as coefficient of variation), in combination with CD71 fluorescence intensity and the percentage of CD117+ erythroid progenitors provided the best discrimination between myelodysplastic syndromes and non-clonal cytopenias (specificity 90%; 95% confidence interval: 84–94%). The high specificity of this marker set was confirmed in the validation cohort (92%; 95% confidence interval: 86–97%). This erythroid flow cytometry marker combination may improve the evaluation of cytopenic cases with suspected myelodysplasia, particularly when combined with flow cytometry assessment of the myelomonocytic lineage.