Prognostic Factors for Survival and Progression to Acute Myeloid Leukemia in Patients with Lower-Risk Myelodysplastic Syndromes. A New Scoring System
Authors: Falantes Jose F , Calderón Cristina , Espigado Ildefonso , Alonso Dora , Noya Antonio Martín , Carrillo Estrella , Martino Maria Luz , Montero Isabel , González Jose , Pérez-Simón Jose Antonio 
Published: October 2019

Abstract
Abstract 1730

Background:
Prognosis of patients (pts) with myelodysplastic syndrome (MDS) is very heterogeneous. Currently, several classifications for MDS as well as different scoring systems are available, that allow to stratify pts in terms of overall survival and risk of transformation to acute myeloid leukemia (AML). However, the subgroup of pts categorized as lower-risk MDS (International Prognostic Scoring System; IPSS, low or intermediate-1 or less than 10% bone marrow blasts) are not properly stratified by IPSS. Factors as age, severity of cytopenias and transfusion dependency (TD) are not considered in classical scoring systems except for TD in World Health Organization (WHO)-Based Prognosis Scoring System (WPSS). Recently, García-Manero et al reported a prognostic score for lower-risk MDS, identifying age (>60y), degree of cytopenias, bone marrow blasts >4% and karyotype as variables which significantly influenced on survival. Three groups of pts were identified with significant differences in estimated survival. Methods: We analyzed baseline characteristics of 335 lower-risk MDS pts from a single institution and their impact on survival and risk for AML progression in a two decade time period (1990–2010). Median age was 72 years (range: 18–93). Most frequent MDS subtypes were refractory anemia (RA) and RA with ringed sideroblasts. Treatment approach included best supportive care and/or observation in 85% pts. Patients on lenalidomide, 5 azacitidine or allogeneic stem cell recipients were excluded from analysis. Baseline characteristics are shown in table 1Results: After a mean follow-up of 39 months, severity of cytopenias: anemia <10 g/dL [HR=1.701 (95% CI: 1.173–2.467), p=0.005], and platelets <50×10e /L [HR=1.853 (95% CI: 1.287–2.667), p=0.001], age >60y [HR=1.909 (95% CI: 1.256–2.902), p=0.002], bone marrow blast percentage (<5% vs 5–9%) [HR=1.288 (95% CI: 1.2–3.045), p=0.006] and TD [HR=1.548 (95% CI: 1.092–2.195), p=0.014], significantly influenced on outcome in multivariate analysis. The combination of these variables allowed to develop a new score system which categorizes classic lower-risk MDS pts in three different groups with median survival of 84 months (95% CI 40–127) for group 1, 41 months for group 2 (95% CI 28–53) and 13 months for group 3 (95% CI 10–15). Estimated 4-year survival was 65%, 38% and 10% for pts in groups 1, 2 and 3 respectively (p<0.001, Figure 1). At last follow-up, 47 pts (14%) progressed to AML. TD and BM blasts 5–9% were the only factors associated with increased risk of AML progression. In addition, this score also stratified pts depending on their risk for AML, estimated at 2 years in 6%, 13% and 31% for groups 1, 2 and 3 respectively (p=0.001, Figure 2). Conclusion: We describe a simplified score, based on data easily available in most institutions, which allows to discriminate different subgroups with different outcome within the lower-risk MDS, identifying in this subset, pts with a poorer prognosis in which an early and more aggressive intervention could possibly be required to improve survival or disease progression.

Abbreviations:
RA, Refractory anemia; RARS, Refractory anemia with ringed sideroblasts; RCMD, Refractory cytopenia with multilineage dysplasia; RAEB-1, Refractory anemia with excess blast; CMML, Chronic myelomonocytic leukemia; MDS-U, Myelodysplastic syndrome unclassificable; ANC, Absolute neutrophil count; IPSS, International Prognostic Scoring System; NA, Not assessable; TD,Transfusion dependency at diagnosis.

Disclosures:
No relevant conflicts of interest to declare.