The myelodysplastic syndromes flow cytometric score: a three-parameter prognostic flow cytometric scoring system

Abstract

The prognosis of myelodysplastic syndromes (MDS) is currently estimated by using the revised International Prognostic Scoring System (IPSS-R). Several studies have shown that further refinement of prognostication for MDS can be achieved by adding flow cytometric parameters. However, widespread implementation of flow cytometry for the prognosis of MDS is hampered by complexity of the analysis. Therefore, the aim of this study was to construct a robust and practical flow cytometric score that could be implemented as a routine procedure. To achieve this, bone marrow aspirates of 109 MDS patients were analyzed by flow cytometry. A second cohort consisting of 103 MDS patients was used to validate the MDS flow cytometric score (MFS). The parameters forming the MFS were sideward light scatter and CD117 expression of myeloid progenitor cells and CD13 expression on monocytes. Three MFS risk categories were formed. Patients with MDS and intermediate MFS scores had significantly better overall survival (OS) compared with the patients with high MFS scores. The MFS further refined prognostication within the IPSS-R low-risk category, by identifying patients with worse OS in case of high MFS. In conclusion, a practical three parameter flow cytometric prognostic score was constructed enabling further refinement of prognostication of MDS.

Determination of the proliferative fractions in differentiating hematopoietic cell lineages of normal bone marrow

“…In the last few years, increasing knowledge is gathered about specific cell surface protein expression patterns during maturation of different hematopoietic cell types, in particular for the process of erythropoiesis (9,10,13,15,16,18,19). During normal hematopoiesis, different blood cell types are produced in the BM depending on physiological requirements.…”

“…Bone marrow is a very heterogeneous tissue population with, next to stromal tissue, different hematopoietic cell lineages including their complete maturation pathways. Recent technological advances in flow cytometry allow for more parameters to be analyzed at an individual cell level, making simultaneous identification of the different cell lineages and even maturation phases of cells possible (9)(10)(11). Normal bone marrow is composed of a number of cell types, each with a regulated phenotype, arranged in a specific spatial organization.…”

Clinical Implication of Multi-Parameter Flow Cytometry in Myelodysplastic Syndromes

“…Moreover, we and others have shown that the number of aberrancies in the FCSS is associated with transfusion dependency, earlier progression of disease, leukemia-free survival and overall survival. A 3-parameter score developed solely for prognosis by Alhan et al [46] has prognostic value beyond the IPSS-R low risk category. They combined CD13 expression on monocytes with sideward light scatter and CD117 expression of myeloid progenitor cells [46].…”

“…A 3-parameter score developed solely for prognosis by Alhan et al [46] has prognostic value beyond the IPSS-R low risk category. They combined CD13 expression on monocytes with sideward light scatter and CD117 expression of myeloid progenitor cells [46]. Other parameters that have negative prognostic value in the lower risk categories are a low progenitor Bcell abundance combined with an increase in regulatory T-cells.…”

Can bone marrow cellularity help in predicting prognosis in myelodysplastic syndromes?

“…This conclusion is supported by a recent study of the Spanish MDS study group, which found that the IPSS‐R model's C index is only 0.65 . Others have suggested using additional parameters, such as immunophenotyping and flow cytometric profiles, but have faced hurdles, including availability, reproducibility, and cost . Recently, it has been proposed to incorporate novel molecular markers into the prognostic systems, and it is likely that the next generation of prognostic algorithms will contain such information .…”