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

Abstract

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

Persistence of immunophenotypically aberrant CD34+ myeloid progenitors is frequent in bone marrow of patients with myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms treated with hypomethylating agents

“…As has been shown previously by others,26 phenotypic changes in maturing myelomonocytic cells in patients undergoing various therapies are less reliable for diagnosis of MDS or MDS/MPN by FCI than assessment of myeloid progenitors. In this study the FCI assay was designed to analyse CD34+ myeloblasts only, an approach similar to our AML MRD assay 16.…”

MDS prognostic scoring systems – Past, present, and future

“…These factors can be assayed with only forward scatter, side scatter, CD45, CD13, and CD33 parameters required. The FCM-score was shown to be both sensitive and specific for diagnosis of the often difficult to diagnose low-grade MDS cases and provided additive prognostic power to the IPSS-R (47, 48). Another study showed that the number of CD34+/CD13+ cells added prognostic value to the IPSS-R (37).…”

Refractory Thrombocytopenia and Neutropenia: A Diagnostic Challenge

“…Moreover, a FC score may help to distinguish MDS from other nonmalignant reactive or secondary cytopenias,42,43 and support the diagnosis of IDUS,24 which may represent a pre-phase of MDS. The Ogata score, based on a 4-color analysis of 13 antigens, has shown a sensitivity of 70% and a specificity of 92% in the whole MDS group 43. For RCUD, the sensitivity was 62%, and a specificity reaching 97% in distinguishing MDS from immune cytopenias 43.…”

“…The Ogata score, based on a 4-color analysis of 13 antigens, has shown a sensitivity of 70% and a specificity of 92% in the whole MDS group 43. For RCUD, the sensitivity was 62%, and a specificity reaching 97% in distinguishing MDS from immune cytopenias 43. Additionally, a FC score is likely to bring prognostic information in MDS even when the blast count is below 5%, with a high correlation with transfusion dependency, cytogenetics, and the IPSS score 44.…”