Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes

Results of a European LeukemiaNET study

Matteo G Della Porta, Cristina Picone, Cristiana Pascutto, Luca Malcovati, Hideto Tamura, Hiroshi Handa, Magdalena Czader, Sylvie Freeman, Paresh Vyas, Anna Porwit, Leonie Saft, Theresia M. Westers, Canan Alhan, Claudia Cali, Arjan A. van de Loosdrecht, Kiyoyuki Ogata

Research output: Contribution to journalArticle

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Abstract

Background The current World Health Organization classification of myelodysplastic syndromes is based on 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. Design and Methods 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 on 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. Results 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. Conclusions A flow cytometric score may help to establish the diagnosis of myelodysplastic syndrome, especially when morphology and cytogenetics are indeterminate.

Original languageEnglish
Pages (from-to)1209-1217
Number of pages9
JournalHaematologica
Volume97
Issue number8
DOIs
StatePublished - Aug 1 2012

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Myelodysplastic Syndromes
Granulocyte Precursor Cells
Learning
Granulocytes
Cytogenetics
Chromosome Aberrations
Bone Marrow
Developmental Bone Disease
Weights and Measures
Sensitivity and Specificity

Keywords

  • Diagnosis
  • Flow cytometry
  • Myelodysplastic syndrome

ASJC Scopus subject areas

  • Hematology

Cite this

Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes : Results of a European LeukemiaNET study. / Porta, Matteo G Della; Picone, Cristina; Pascutto, Cristiana; Malcovati, Luca; Tamura, Hideto; Handa, Hiroshi; Czader, Magdalena; Freeman, Sylvie; Vyas, Paresh; Porwit, Anna; Saft, Leonie; Westers, Theresia M.; Alhan, Canan; Cali, Claudia; van de Loosdrecht, Arjan A.; Ogata, Kiyoyuki.

In: Haematologica, Vol. 97, No. 8, 01.08.2012, p. 1209-1217.

Research output: Contribution to journalArticle

Porta, MGD, Picone, C, Pascutto, C, Malcovati, L, Tamura, H, Handa, H, Czader, M, Freeman, S, Vyas, P, Porwit, A, Saft, L, Westers, TM, Alhan, C, Cali, C, van de Loosdrecht, AA & Ogata, K 2012, 'Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: Results of a European LeukemiaNET study', Haematologica, vol. 97, no. 8, pp. 1209-1217. https://doi.org/10.3324/haematol.2011.048421
Porta, Matteo G Della ; Picone, Cristina ; Pascutto, Cristiana ; Malcovati, Luca ; Tamura, Hideto ; Handa, Hiroshi ; Czader, Magdalena ; Freeman, Sylvie ; Vyas, Paresh ; Porwit, Anna ; Saft, Leonie ; Westers, Theresia M. ; Alhan, Canan ; Cali, Claudia ; van de Loosdrecht, Arjan A. ; Ogata, Kiyoyuki. / Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes : Results of a European LeukemiaNET study. In: Haematologica. 2012 ; Vol. 97, No. 8. pp. 1209-1217.
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AU - Picone, Cristina

AU - Pascutto, Cristiana

AU - Malcovati, Luca

AU - Tamura, Hideto

AU - Handa, Hiroshi

AU - Czader, Magdalena

AU - Freeman, Sylvie

AU - Vyas, Paresh

AU - Porwit, Anna

AU - Saft, Leonie

AU - Westers, Theresia M.

AU - Alhan, Canan

AU - Cali, Claudia

AU - van de Loosdrecht, Arjan A.

AU - Ogata, Kiyoyuki

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N2 - Background The current World Health Organization classification of myelodysplastic syndromes is based on 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. Design and Methods 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 on 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. Results 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. Conclusions A flow cytometric score may help to establish the diagnosis of myelodysplastic syndrome, especially when morphology and cytogenetics are indeterminate.

AB - Background The current World Health Organization classification of myelodysplastic syndromes is based on 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. Design and Methods 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 on 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. Results 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. Conclusions A flow cytometric score may help to establish the diagnosis of myelodysplastic syndrome, especially when morphology and cytogenetics are indeterminate.

KW - Diagnosis

KW - Flow cytometry

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