Diagnostic flow cytometry for low‐grade myelodysplastic syndromes

Abstract

It has long been considered that flow cytometry (FCM) has little role in clinical practice in the diagnosis of myelodysplastic syndromes (MDS). However, recent advances in the analytical method and knowledge of MDS FCM are changing this stereotype. This paper reviews the concept and current status of FCM in the diagnosis of low-grade MDS. The diagnosis of low-grade MDS in the absence of ringed sideroblasts and chromosomal aberration is not always straightforward, and a report from a recent international working conference has proposed FCM as an adjunctive diagnostic test for such cases. Currently, only a limited number of laboratories are applying FCM to the diagnosis of MDS. Furthermore, standard analytical methods in FCM for MDS have not been established, and no single FCM parameter is sufficiently sensitive and specific to make the diagnosis of MDS. To establish MDS FCM as a widely accepted, dependable diagnostic tool, prospective studies should increase flow parameters that can be analysed reproducibly and determine their sensitivity and specificity, either alone or in combination. CD34+ cell-related parameters that are applicable for diagnosing low-grade MDS in many laboratories are introduced here.

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

“…Importantly, when comparing different methods to define B-cell progenitors and myeloblasts, the analysis based on SSC and CD45 characteristics was found to have the highest efficiency in discriminating patients with marrow dysplasia with respect to patients with non-clonal cytopenia, and to be highly reproducible by different FCM operators. 19,27 Several other immunophenotypic abnormalities on MDS CD34…”

Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group

“…To circumvent problems regarding hemodilution in the enumeration of progenitor B cells, it is recommended to express these cells as fraction of all CD34 þ blast cells. 33,54 The relevance of a decreased percentage of B-cell progenitors is not yet known, as it is also seen in the elderly population without MDS. Interestingly, a decreased relative amount of progenitor B cells (o5% of CD34 þ cells) was recently introduced as one of the cardinal parameters in a model to distinguish low-risk MDS from non-clonal cytopenias.…”

Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes

“…The cut-off level for abnormally increased blast counts by FCM in MDS may be closer to 3% of total nucleated cells in contrast to the 5% currently used by morphology. 4,6,35,39 In addition, the detection and enumeration of circulating (aberrant) blasts is of increasing interest since some data suggest that the presence of blasts in peripheral blood in RA+/-RS may influence OS or may be associated with an increased risk of leukemic transformation and post-transplant relapse. 5,40,41 The effect of secondary myelofibrosis, which may an independent risk factor, on the presence of circulating blasts or myeloid progenitor cells is not yet clear.…”

“…44,45 To circumvent problems regarding hemodilution in the enumeration of progenitor B cells, it was recommended that these cells are expressed as a fraction of all (CD34 + ) blast cells. 39 …”