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 & 10 others 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, IMDSFlow Working Group

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)308-319
Number of pages12
JournalHaematologica
Volume102
Issue number2
DOIs
Publication statusPublished - 2017

Cite this

Westers, T. M., Cremers, E. M. P., Oelschlaegel, U., Johansson, U., Bettelheim, P., Matarraz, S., ... IMDSFlow Working Group (2017). Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group. Haematologica, 102(2), 308-319. https://doi.org/10.3324/haematol.2016.147835
Westers, Theresia M. ; Cremers, Eline M.P. ; Oelschlaegel, Uta ; Johansson, Ulrika ; Bettelheim, Peter ; Matarraz, Sergio ; Orfao, Alberto ; Moshaver, Bijan ; Brodersen, Lisa Eidenschink ; Loken, Michael R. ; Wells, Denise A. ; Subirá, Dolores ; Cullen, Matthew ; te Marvelde, Jeroen G. ; van der Velden, Vincent H.J. ; Preijers, Frank W.M.B. ; Chu, Sung Chao ; Feuillard, Jean ; Guérin, Estelle ; Psarra, Katherina ; Porwit, Anna ; Saft, Leonie ; Ireland, Robin ; Milne, Timothy ; Béné, Marie C. ; Witte, Birgit I. ; Della Porta, Matteo G. ; Kern, Wolfgang ; van de Loosdrecht, Arjan A. ; IMDSFlow Working Group. / Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group. In: Haematologica. 2017 ; Vol. 102, No. 2. pp. 308-319.
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title = "Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group",
abstract = "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.",
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Westers, TM, Cremers, EMP, Oelschlaegel, U, Johansson, U, Bettelheim, P, Matarraz, S, Orfao, A, Moshaver, B, Brodersen, LE, Loken, MR, Wells, DA, Subirá, D, Cullen, M, te Marvelde, JG, van der Velden, VHJ, Preijers, FWMB, Chu, SC, Feuillard, J, Guérin, E, Psarra, K, Porwit, A, Saft, L, Ireland, R, Milne, T, Béné, MC, Witte, BI, Della Porta, MG, Kern, W, van de Loosdrecht, AA & IMDSFlow Working Group 2017, 'Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group' Haematologica, vol. 102, no. 2, pp. 308-319. https://doi.org/10.3324/haematol.2016.147835

Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group. / Westers, Theresia M.; Cremers, Eline M.P.; Oelschlaegel, Uta; Johansson, Ulrika; Bettelheim, Peter; Matarraz, Sergio; Orfao, Alberto; Moshaver, Bijan; Brodersen, Lisa Eidenschink; Loken, Michael R.; Wells, Denise A.; Subirá, Dolores; Cullen, Matthew; te Marvelde, Jeroen G.; van der Velden, Vincent H.J.; Preijers, Frank W.M.B.; Chu, Sung Chao; Feuillard, Jean; Guérin, Estelle; Psarra, Katherina; Porwit, Anna; Saft, Leonie; Ireland, Robin; Milne, Timothy; Béné, Marie C.; Witte, Birgit I.; Della Porta, Matteo G.; Kern, Wolfgang; van de Loosdrecht, Arjan A.; IMDSFlow Working Group.

In: Haematologica, Vol. 102, No. 2, 2017, p. 308-319.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group

AU - Westers, Theresia M.

AU - Cremers, Eline M.P.

AU - Oelschlaegel, Uta

AU - Johansson, Ulrika

AU - Bettelheim, Peter

AU - Matarraz, Sergio

AU - Orfao, Alberto

AU - Moshaver, Bijan

AU - Brodersen, Lisa Eidenschink

AU - Loken, Michael R.

AU - Wells, Denise A.

AU - Subirá, Dolores

AU - Cullen, Matthew

AU - te Marvelde, Jeroen G.

AU - van der Velden, Vincent H.J.

AU - Preijers, Frank W.M.B.

AU - Chu, Sung Chao

AU - Feuillard, Jean

AU - Guérin, Estelle

AU - Psarra, Katherina

AU - Porwit, Anna

AU - Saft, Leonie

AU - Ireland, Robin

AU - Milne, Timothy

AU - Béné, Marie C.

AU - Witte, Birgit I.

AU - Della Porta, Matteo G.

AU - Kern, Wolfgang

AU - van de Loosdrecht, Arjan A.

AU - IMDSFlow Working Group

PY - 2017

Y1 - 2017

N2 - 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.

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