Percentage of Erythroid Cells in Bone Marrow at Diagnosis As a New Prognostic Factor in Patients with Myelodysplastic Syndrome
Authors: Villalba Ana , Senent Leonor , Alonso Esther , Mora Elvira , Bernal Del Castillo Teresa , Ramos Fernando , Leonor Arenillas , Vicente Ana , Orero Teresa , Tormo Mar , Ardanaz Teresa , Marco Victor , Díez-Campelo Maria , Jerez Andres , Montoro Julia , Arrizabalaga Beatriz , Lluch Rafael , de Paz Raquel , Font Patricia , Lorenzo Ignacio , Sanz Guillermo 
Published: October 2019

Abstract
Introduction
Risk assessment is essential for guiding therapy in patients with myelodysplastic syndromes (MDS). Currently, the most widely used prognostic scoring models are the International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R). The prognostic relevance of the percentage of erythroid precursors (EP) in bone marrow (BM) and its relationship with other biological characteristics has been poorly studied, although it has been proposed that a very low percentage of EP in BM may represent a cohort of patients with potentially adverse outcome. Our main aim was to analyze the biological and clinical features of MDS patients according to the percentage of EP in BM at diagnosis and evaluate its prognostic value on survival.
Patients and Methods
Data from 4,791 de novo MDS patients from the MDS Spanish Registry with available cytogenetics were collected. All patients included were diagnosed based on the 2008 WHO criteria and risk stratification was performed following the IPSS-R. Patients were distributed, according to the percentage of EP in BM, into three groups: less than 15% (EP<15%), between 15% and 49% (EP 15-49%) and equal or more than 50% (EP>49%).
Proportions were compared by the Chi-square test. Survival curves were constructed by Kaplan-Meier method and differences between curves were evaluated by log rank tests. Multivariable analysis of survival was performed using Cox's proportional hazards regression model. P-values <0.05 were considered as statistically significant. All statistical analyses were performed by the R software.
Results
The 4,791 cases were grouped according to the percentage of erythroid cells in BM at diagnosis. In Table 1 are displayed the clinical and biological characteristics of the patients in the whole series and in the three groups based on the EP percentage in BM. The group with EP<15% in BM showed a significantly greater number of cytopenias at diagnosis, a higher number of peripheral blood (PB) and BM blasts, and a higher percentage of patients classified in MDS subtypes with excess blasts. The EP>49% group presented higher rates of patients with refractory anemia with ring sideroblasts (RARS), lower number of PB and BM blasts, and more frequent high-risk cytogenetics. Conversely, the intermediate EP group with EP 15-49% showed less number of cytopenias, higher frequency of good-prognosis cytogenetics, and lower percentage of patients in higher-risk IPSS-R categories.
Survival analyses confirmed that age, blast percentage in PB and BM, and IPSS-R cytogenetics are significantly associated with worse survival. A striking difference in survival within groups according to percentage of EP was also found, recognizing EP percentage as an independent risk factor for survival of MDS patients in multivariate analysis. Patients with EP<15% in BM experienced a significantly shorter OS (median, 28 months) in both univariable (P<0.0001) and multivariable analysis (P<0.0001) (Table 2 and Figure 1). The best survival was found for patients with EP 15-49% with a median survival of 58 months. The group with EP>50% in BM had also worse survival than the intermediate group, showing a median survival of 47 months (hazard ratio, 0.79; 95% CI, 0.67 to 0.93; P < 0.005).
Conclusions
Our study proves the prognostic impact of the percentage of erythroid precursors in bone marrow in MDS patients, providing evidence that the presence of EP <15% in BM is an independent risk factor for survival.

Disclosures
Díez-Campelo: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.