Deutsches MDS-Forum 2010 - Wo wir stehen & wohin wir gehen
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Grundlagen und Updates

FACS in MDS - indispensable, promising or useless?

Abstract | Vortrag
Autor: Prof. Dr. med. A.A. van de Loosdrecht, VU University Medical Center, Amsterdam
Quellenangabe: Deutsches MDS-Forum 2010, Göttingen
Stand: 20.09.2010

The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders, characterized by cytopenia(s), dysplasia and a propensity to evolve into acute myeloid leukemia. The International Prognostic Scoring System (IPSS) and WHO-based prognostic scoring system (WPSS) provide prognostic information. However, even if patients are allocated in the same risk category, their clinical course remains heterogeneous. Recent developments in the treatment of MDS require refinement of prognostication and identification of patients, who might benefit from treatment with potentially disease modifying agents such as lenalidomide or azacitidine. Flow cytometry (FC) is emerging as a valuable technique for the diagnosis and prognosis of MDS. Recently, we demonstrated that flow cytometric analysis of BM in low and int-1 risk MDS is instrumental to identify clinically relevant subgroups to select for treatment with Epo/G-CSF. (Westers et al, Blood 2010) Previously, it was reported that a flow cytometric scoring system (FCSS) is predictive for worse outcome in MDS. (Wells et al, Blood 2003, Van de Loosdrecht et al, Blood 2008) The FCSS is a scoring system that allows for a numerical display of immunophenotypic aberrancies in the (im)mature myelo-monocytic lineage. Scores are generated by enumerating abnormalities; a high score reflects a high number of aberrancies. The FCSS correlates with IPSS and WPSS although no significant correlations are shown with cytogenetic risk subgroups.This indicates that the FCSS and cytogenetics may provide separate prognostic information in MDS. Neutrophil granularity corresponding with side scatter by FC was significantly decreased in MDS patients compared with healthy volunteers (p<0.0001). In the RA(RS) and RCMD(RS) category, 40% of patients expressed an aberrant marker such as CD5, CD7 and/or CD56 on myeloid progenitors. Interestingly, the majority of MDS patients who were transfusion dependent or progressive, had aberrant expression of CD5, CD7 and/or CD56 on myeloid progenitors compared with MDS patients without aberrant marker expression. When the cumulative amount of all aberrancies in the (im)mature myelo-monocytic cells were taken into account, transfusion dependent patients had significantly more aberrancies than transfusion independent MDS patients. In addition, the majority of RA(RS) patients has multilineage dysplasia as detected by FC, which might be of prognostic relevance. Although the FCSS correlates with current prognostic systems, a striking heterogeneity remains within prognostic subgroups. Therefore, the FCSS and detection of aberrant myeloid progenitors can provide refined prognostication by identification of patients at risk for transfusion dependency and adverse clinical outcome, independent of current classification systems.



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