Evaluation of Prognostic Variables and Scoring Systems in Normal Karyotyped Myelodisplastic Patients
Authors: Belli Carolina B , Lardo Mabel , Arrossagaray Guillermo , Sakamoto Juan Francisco , Flores María Gabriela , Aranguren Pedro Negri , Bengio Raquel Maria , Larripa Irene , Bianco Pedro Raul Perez 
Published: April 2020

Abstract
Myelodysplastic Syndrome (MDS) comprises a group of heterogeneous hematological disorders with variable risk of leukemic evolution (LE) and short survival (SV). According to French-American-British (FAB) classification, MDS are divided into five morphological entities and the World Health Organization reclassified them eliminating Refractory Anemia (RA) with Excess of Blast in transformation (RAEBt) and Chronic Myelomonocytic Leukemia (CMML), among other changes. Around 40–60% of patients shows normal karyotype at diagnosis and, despite this finding which is associated with good prognosis, some of them show poor outcome. The aim of this study was to evaluate different variables and prognostics scoring systems in an overall population (OP) of normal karyotyped MDS patients and in the reduced population (RP) after eliminating RAEBt and CMML subgroups. This retrospective study was performed in a population of 152 MDS patients with normal karyotype at diagnosis distributed according to FAB into 59% RA/RA with ringed sideroblast, 23% RA with excess of blasts, 5% RAEBt and 13% CMML. The OP’s median age was 67 (20–89) years with a sex ratio (M/F) of 1.53. The median follow-up was 25.7 (1–266) months (m) and there were 31 (20%) events of LE and 65 (43%) related-MDS death during this period. The OP showed a median SV of 57 m and time to LE (25%) of 44 m vs. 63 and 124 m, respectively for the RP. Age, sex, percentage of bone marrow (BM) blast, hemoglobin (Hb) level, platelets count and number of cytopenias were significant predictive variables for prognosis in both populations (Kaplan-Meier and Long-Rank test, p&lt;0.05). Despite all applied scoring systems allowed to difference groups of risk, patient distribution among them showed variations which were more evident in the Intermediate ones. Multivariate analysis (Cox proportional Hazard Model, p&lt;0.05) established that age, Hb level and % BM blast were the most important predictors for SV. Therefore, a new scoring system was developed coding % BM blast 0 if &lt;5, 0.5 if 5–9, 1 if 10–19 and 1.5 if ≥20, age 0 if ≤60 and 0.5 if &gt;60 years, Hb level 0 if ≥10 and 0.5 if &lt;10g/dL. Three groups of risk were defined: Low (0+0.5), Intermediate (1+1.5) and High (&gt;1.5) with median SV of 131, 32 and 13 m for the OP vs. 131, 43 y 18 m for the RP, respectively. Additionally, confirmed that IPSS includes better variables for LE, determining 3 groups of risk: Low, Intermediate and High (Intermediate-2 + High) with time to LE (25%) of &gt;130, 22 and 4 m for the OP vs. &gt;130, 39 y 21 m for the RP, respectively. Results showed that SV and LE risk should be evaluated separately in patients with normal karyotype using different variables to predict each one, at least in MDS-FAB classified patients or in those that present less than 20% of BM blasts and monocite counts lower than 1000/μL. These results would be helpful to develop better risk-adapted therapeutic strategies for MDS patients with normal karyotype.