Flow Cytometric Scoring System as a Diagnostic and Prognostic Tool In Myelodysplastic Syndromes
Authors: Chu Sung-Chao , Wang Tso-Fu , Li Chi-Cheng , Kao Ruey-Ho , Li Dian-Kun , Su Yu-Chieh , Loken Michael R. 
Published: October 2019

Abstract
Abstract 1875

Introduction:
The aim of this study is to validate the clinical utility of a flow cytometric scoring system (FCSS) (1)in the diagnosis and prognosis of MDS by quantifying myeloid and monocytic dyspoiesis and correlating the accumulation of abnormalities to clinical outcome.

Methods:
The BM samples were characterized by the FCSS from 56 consecutive, newly diagnosed MDS patients who were morphologically classified as RA (n=3), MDS-U (n=1), RCMD/RCMD-RS (n=32), RAEB-1 (n=12) and RAEB-2 (n=8) from January 2005 to December 2009. Three-color FCM was performed on total nonerythroid BM cells with a standardized panel of monoclonal antibodies (Table 1). The final FCSS was based on the independent analysis of data by 2 investigators (S.C.C., T.F.W.,) who were blinded to MDS/non-MDS category and clinical outcomes. The FCSS were categorized as normal/mild (0 or 1 point), moderate (2 or 3 points), or severe (4 or more points). The results of FCSS were compared with findings in 27 non-MDS cytopenic patients as the control, including diagnosis of aplastic anemia (n=7), iron deficiency anemia (n=3), folic acid or vitamin B12 deficiency anemia (n=6) and idiopathic thrombocytopenia purpura (n=11). FCSS scores were retrospectively compared with marrow blast counts, cytogenetics, hematologic parameters, IPSS and WHO categorization to assess the utility in diagnosis and prognosis of MDS. Follow-up of patients continued until May 2010, with mortality observed in 30 (54%) patients. The patient characteristics are summarized in Table 2. Nearly all MDS patients underwent supportive care rather than hypomethylation agents(n=3), chemotherapy(n=4) or haematopoietic stem cell transplantation(n=0).

Results:
The FCSS scores were significantly higher in patients with MDS than those in the non-MDS control (3 vs. 0, P < .0001). A flow score of 2 or more allowed for a specificity of 100% with 75% sensitivity in diagnosing MDS.
The FCSS scores correlated directly with IPSS scores (n=40, R=.5327, P =.0004) and WHO classification (n= 56, R=.5163, P<.0001) but did not correlated with IPSS cytogenetic risk categories (n=40, P= .7738). The median survival were 6 months, 19 months and not reach for MDS patients with severe, moderate and mild FCSS scores, respectively (n=56, P = .0018)(Figure 1). The Multivariate analyses using Cox proportional hazard model in a stepwise manner demonstrated the FCSS risk categories was an independent prognostic factor (P=.0020) after adjusting for sex, age (above 70 year-old or not) and IPSS risk categories. Furthermore, among 32 patients classified as RCMD/RCMD-RS, the median survival were 2 months, 13 months and not reach for patients with severe, moderate and mild FCSS scores, respectively (n=32, P = .0045) (Figure 2).

Conclusion:
These results demonstrate that quantifying aberrancies in myelomonocytic lineage by FCSS is very useful in MDS diagnosis. As shown in a bone marrow transplant study the FCSS also predicts outcome in conventionally treated patients and may give a more accurate prognosis especially among patients classified as RCMD subgroup.

Reference:
(1) Wells, DA et Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation Blood 102: 394–403, 2003.

Disclosures:
No relevant conflicts of interest to declare.