Impact of Red Cell Distribution Width on Dysplasia and Clinical Outcome in 66 Patients with Myelodysplastic Syndrome without Increased Blasts
Authors: Baba Yuta , Saito Bungo , Shimada Shotaro , Sasaki Yohei , Murai So , Abe Maasa , Fujiwara Shun , Arai Nana , Kawaguchi Yukiko , Kabasawa Nobuyuki , Tsukamoto Hiroyuki , Uto Yui , Yanagisawa Kouji , Hattori Norimichi , Harada Hiroshi , Nakamaki Tsuyoshi 
Published: October 2019

Abstract
Both clonal hematopoiesis as defined by genomic alteration and morphological cell dysplasia is a hallmark of pathology of myelodysplastic syndrome (MDS). Studies showed that, red cell distribution width (RDW), a quantitative non-subjective index of red cell anisocytosis, has diagnostic significance in anemia associated with MDS.
Our recent study showed that increase of RDW has close association with dyserythropoiesis and also shorter overall survival (OS) in refractory anemia (Leuk Res 2018;67:56-59). To explore the clinical significance of RDW in MDS without increased blasts, we examined the details of correlation between RDW and morphological dysplasia which characterize MDS.
We retrospectively analyzed 101 MDS patients, including 66 patients without increased blasts (blasts in the bone marrow of less than 5% and the peripheral blood of 1% or less). RDW was calculated using automated blood cell analyzer. Dysplasia was assessed according to the WHO 2008 classification by different two investigators. 100 cells (at least 25 cells) of myeloid and erythroid series were counted. At least 25 cells of megakaryocyte were also counted. Karyotype of bone marrow cells was analyzed by using routine G-band technique and categorized according to MDS cytogenetic scoring system. Correlations of RDW and clinical variables were analyzed. Based on previous study, MDS patients was divided into two groups, RDW-H (RDW was 15% or more, 48 cases) and RDW-L (RDW was lower than 15%, 18 cases). Comparisons of dysplasia or OS between these two groups were analyzed.
In MDS without increase of blasts, weak inverse correlation was found between RDW and hemoglobin (rs = −0.31, P = 0.01). RDW was correlated with the presence of ring sideroblasts (RS) in the bone marrow (rs = 0.40, P = 0.001), and also weakly correlated with budding of nucleus of erythroblasts (rs = 0.33, P = 0.007). Dysgranulopoiesis was less observed than either dyserythropoiesis or dysmegakaryopoiesis (P <0.001, P <0.001). RDW was not significantly different between groups with karyotype risk category (P = 0.08).
Table showed the subtype of MDS, details of morphological dysplasia. Between two groups, RDW-H showed significantly higher percentages of dyserythropoiesis, dysgranulopoiesis, and dysmegakaryopoiesis.
The increased RDW (≥15.0%) was associated with shorter OS (P = 0.02) (hazard ratio, 1.15e + 9 (95% confidence interval = 2.49-2.49)) (Figure). In contrast, there was no association between RDW and OS in MDS patients with increased blasts.
Earlier studies showed increase of RDW was evident in refractory anemia with ring sideroblasts (RARS) which showed erythrocyte anisocytosis called dimorphism. Revised WHO classification (2017) defined MDS-RS with single lineage dysplasia (MDS-RS-SLD) which is characterized with specific mutation of splicing factors, such as SF3B1 and with favorable prognosis. This classification also defined MDS-RS with multi lineage dysplasia (MDS-RS-MLD) which has additional dysplasia in myeloid and/or megakaryocyte lineage in addition to RS. Pathology of MDS-RS-MLD is still to be remained.
Our findings partly agree the earlier observations, showing close association between red cell anisocytosis evaluated with increase of RDW and the presence of RS. Furthermore, RDW-H group contained MDS with dysplasia of myeloid and/or megakaryocyte lineage not limited to the erythroid dysplasia(s) with RS. RDW could discriminate MDS-MLD with poor prognosis from MDS-SLD with favorable prognosis.
To explore the significance of RDW in MDS, it is necessary to study large number of patient combined with genetic analysis. Nevertheless, RDW is potentially simple and useful laboratory parameters in clinical practice in MDS, representing hematopoietic defect (ineffective hematopoiesis), associated with iron metabolism and hemoglobin synthesis in MDS.

Disclosures
No relevant conflicts of interest to declare.