Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment

Westers, Theresia M.; Alhan, Canan; Chamuleau, Martine E.D.; Vorst, Maurice J. D. L. van der; Eeltink, Corien; Ossenkoppele, Gert J.; Loosdrecht, Arjan A. van de

doi:10.1182/blood-2009-08-239749

Cited by 87 publications

(69 citation statements)

References 32 publications

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“…[14][15][16] Consistent immunophenotypic aberrations reported in the CD34 + cell compartment in MDS are: an increase of the myeloid-committed CD34 + population, 10,15,17 a decrease of B-cell progenitors, 15,18 co-expression of stem cell-and late stage-myeloid antigens, expression of lymphoid antigens 7,8,11 and abnormal CD45 expression. 15 We previously reported that data for three of these parameters (percentage of myeloblasts, percentage of Bcell progenitors, and myeloblast CD45 expression) together with the evaluation of side scatter (SSC) on granulocytes are reproducible in many laboratories when measured by methods ensuring little inter-operator variability, 19,20 and when combined are able to differentiate correctly patients with MDS from patients with non-clonal cytopenia.…”

Section: Introductionmentioning

confidence: 89%

Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study

Porta¹,

Picone²,

Pascutto³

et al. 2012

Haematologica

142

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The online version of this article has a Supplementary Appendix. BackgroundThe 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 MethodsWe 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. ResultsWith 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. ConclusionsA flow cytometric score may help to establish the diagnosis of myelodysplastic syndrome, especially when morphology and cytogenetics are indeterminate. LeukemiaNET study. Haematologica 2012;97(8):1209-1217. doi:10.3324/haematol.2011 This is an open-access paper. Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study

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Section: Introductionmentioning

confidence: 89%

Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study

Porta¹,

Picone²,

Pascutto³

et al. 2012

Haematologica

142

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“…7 Abnormalities detected by flow cytometry in myelomonocytic, erythroid and/or myeloid blast cells [8][9][10][11][12][13][14][15][16][17] can be of diagnostic and prognostic relevance in adult MDS. [18][19][20] In pediatric MDS, only a limited number of flow cytometric immunophenotyping studies have been reported. In advanced pediatric MDS, CD7 expression on myeloid blast cells was described to correlate with dismal survival.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood

Aalbers¹,

Heuvel‐Eibrink²,

Baumann³

et al. 2014

Haematologica

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Refractory cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory cytopenia from the immune-mediated bone marrow failure syndrome (very) severe aplastic anemia can be challenging. Flow cytometric immunophenotyping of bone marrow has been shown to be a valuable diagnostic tool in differentiating myelodysplastic syndrome from non-clonal cytopenias in adults. Here, we performed the first comprehensive flow cytometric analysis of immature myeloid, lymphoid cells and erythroid cells, and granulocytes, monocytes, and lymphoid cells in bone marrow obtained from a large prospective cohort of 81 children with refractory cytopenia. Children with refractory cyotopenia had a strongly reduced myeloid compartment, but not as severe as children with aplastic anemia. Furthermore, the number of flow cytometric abnormalities was significantly higher in children with refractory cytopenia than in healthy controls and in children with aplastic anemia, but lower than in advanced myelodysplastic syndrome. We conclude that flow cytometric immunophenotyping could be a relevant addition to histopathology in the diagnosis of refractory cytopenia of childhood. (The multi-center studies EWOG-MDS RC06 and EWOG-MDS 2006 are registered at clinicaltrials.gov identifiers 00499070 and 00662090, respectively).

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“…Olivier Kosmider, 1 Marie Passet, 1 Valeria Santini,2 Uwe Platzbecker, 3 Valérie Andrieu, 4 Gina Zini, 5 Odile Beyne-Rauzy, 6 Agnès Guerci, 7 Erico Masala, 8 Enrico Balleari, 9 Ekaterina Bulycheva, 3 François Dreyfus, 10 Pierre Fenaux, 11 Michaela Fontenay, 1 …”

Section: Letters To the Editorunclassified

“…[1][2][3] Main consensus prognostic factors of better response to ESA include low or int-1 IPSS, low RBC transfusion burden, and low serum EPO (sEPO). 4 Other reported prognostic factors for response to ESA include marrow multilineage dysplasia, flow cytometry scoring, 5 ERK and STAT5 phosphorylation in erythroblasts, 6,7 and IPSS-R. 8 Somatic mutations are found in up to 80% of MDS. Many of them and/or their number have been correlated with outcome irrespective of treatment, 9 or after specific treatments like allogeneic SCT 10 or hypomethylating agents.…”

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confidence: 99%

Are somatic mutations predictive of response to erythropoiesis stimulating agents in lower risk myelodysplastic syndromes?

et al. 2016

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Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment

Cited by 87 publications

References 32 publications

Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study

Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study

Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood

Are somatic mutations predictive of response to erythropoiesis stimulating agents in lower risk myelodysplastic syndromes?

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