Considering Bone Marrow Blasts from Nonerythroid Cells Improves the Prognostic Evaluation of Myelodysplastic Syndromes with Ring Sideroblasts
Authors: Arenillas Leonor , Calvo Xavier , Luño Elisa , Senent Leonor , Alonso Ester , Ramos Fernando , Ardanaz Maria Teresa , Pedro Carme , Tormo Mar , Marco Victor , Montoro Julia , Díez-Campelo María , Brunet Salut , Arrizabalaga Beatriz , Xicoy Blanca , Andreu Rafael , Bonanad Santiago , Jerez Andres , Nomdedeu Meritxell , Ferrer Ana , Sanz Guillermo , Florensa Lourdes 
Published: October 2019

Abstract
Introduction: As showed in a recent study of our group, considering bone marrow (BM) blasts from nonerythroid cellularity (NECs) improves the prognostic evaluation of MDS (Arenillas et al, J Clin Oncol 2016). By enumerating blasts from NECs, 12% of MDS patients diagnosed within WHO categories with less than 5% BM blasts were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in the initial categories. Refractory anemia with ring sideroblasts (RARS) and refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS) have shown an special good outcome in different studies. As MDS with ring sideroblasts (MDS-RS) usually present a high percentage of BM erythroblasts, considering BM blasts from NECs could imply a risk overestimation of this subset of patients.
Aim: we evaluated the relevance of considering BM blasts from NECs or from total nucleated cells (TNCs) on classification and prognostication of the group of patients diagnosed with MDS-RS.
Methods: We retrospectively analyzed 3,924 de novo MDS diagnosed according to WHO 2001 and 2008 classifications from the MDS Spanish registry. 1,045 patients presented less than 5% BM blasts from TNCs and equal or greater than 15% BM ring sideroblasts, fulfilling current definition for RARS (WHO 2001 and 2008) and RCMD-RS (WHO 2001). Moreover 1,233 patients with equal or greater than 5% BM ring sideroblasts and less than 5% BM blasts were analyzed in order to explore the future definition of WHO 2016, that considered as MDS-RS those patients with 5%-<15% BM ring sideroblasts if SF3B1 mutation is present. This was a tentative analysis since SF3B1 mutation information was not available in our series. Percentage of BM blasts from NECs was calculated as follows: [%BM blasts from TNCs/(100 - %BM erythroblasts) x 100]. Survival curves were constructed by using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox regression analysis were also implemented.
Results: Median age at diagnosis of MDS-RS was 76y (25-101) and 59% were males. Estimated median follow-up, as calculated by reverse Kaplan-Meier method, was 50.1 months (95% CI, 45.5-54.7) and median OS was 96.5 months. By enumerating blasts from NECs, 10% of MDS-RS patients were reclassified into categories with equal or greater than 5% BM blasts and showed a poorer overall survival (OS) than did those who remained in initial categories (median OS, 68.1 vs 97.6 months, P=0.025; Hazard ratio (HR): 1.41; 95%CI: 1.04-1.91; p=0.026). After adjusting the survival analysis by IPSS cytogenetic risk groups, the prognostic impact of BM blasts considered from NECs maintained its significance (HR: 1.37; 95%CI: 1.01-1.85; p=0.045). Similar results were observed applying this method to the group of MDS patients with equal or greater than 5% BM ring sideroblasts and less than 5% BM blasts. By considering blasts from NECs, 10% of this subset of patients were reclassified into categories with equal or greater than 5% BM blasts and showed a poorer OS than did those who remained in initial categories (median OS, 60.2 vs 85.8 months, P=0.003; HR: 1.51; 95%CI: 1.15-1.97; p=0.003; HR adjusted for IPSS cytogenetics: 1.46; 95%CI: 1.12-1.92; p=0.006).
Conclusion: considering bone marrow blasts from nonerythroid cells improves the prognostic evaluation of MDS with ring sideroblasts.
Written on behalf of the Grupo Español de Síndromes Mielodisplasicos (GESMD).

Disclosures
No relevant conflicts of interest to declare.