A reclassification of Myelodysplastic Syndrome (MDS) patients of RAEB-1 subgroup according to IPSS-R improves discrimination of high risk patients and better predicts overall Survival. A retrospective analysis of 49 Patients
Authors: Cermak Jaroslav , Mikulenková Dana , Brezinova Jana , Michalova Kyra 
Published: October 2019

Abstract
Abstract 4957
Refractory anemia with excess of bone marrow (BM) blasts up to 10% (RAEB-1) has been generally considered a MDS subgroup with moderate prognosis and most of the patients are not indicated for immediate intensive treatment. In our retrospective study, 27 out of 49 patients with RAEB-1 had intermediate-1 (IM-1) risk and 22 patients were classified as intermediate-2 (IM-2) risk group according to the IPSS. Nevertheless, median survival of untreated patients with RAEB-1. was only 5. 0 months compared to 36. 3 months in untreated patients with ≤ 5% BM blasts at the time of diagnosis (P<0. 0001). After reclassification of patients according to revised IPSS (IPSS-R) only 14 patients remained in the intermediate (IM) risk group and 3 patients were even shifted to the low (L) risk group. On the other hand, 14 patients have fulfilled criteria for high (H) risk group and 18 out of 49 patients (37%) had very high (VH) risk score. Median survival of patients treated with low dose chemotherapy (9. 0 months) or hydroxyurea (8. 8 months) was not significantly different from that in patients who received supportive care only. A significant benefit in median survival was observed after combination chemotherapy (14. 0 months) or after stem cell transplantation (SCT) (17. 0 months). SCT was the only treatment connected with prolonged survival, nevertheless, estimated 5 years overall survival of 31. 2 months was significantly inferior (P=0. 02) to that of transplanted patients not only with ≤ 5% BM blasts (62. 2 months) but also with > 10% BM blasts (55. 6 months). Univariate analysis using Kaplan-Meier curves and log-rank2 test revealed as significant variables affecting overall survival: poor cytogenetics IPSS subgroup (P=0. 001), ECOG > 2 (P=0. 001), IM-2 IPSS risk group (P=0. 001), treatment with SCT (P=0. 003), platelet (PLT) count < 20×109/l (P=0. 004), high or very high IPSS-R risk group (P=0. 01) and age > 60 years (P=0. 03). The most important independent variable for determining overall survival (studied by Cox regression multivariate analysis) was poor cytogenetics according IPSS (P=0. 0001, χ2=52. 623), followed by PLT count < 20×109/l (P=0. 001, χ2= 10. 382), and ECOG > 2 (P=0. 002, χ2= 9. 794). Our data suggest that RAEB-1 represent a poor prognostic MDS subgroup with similar outcome as advanced MDS with > 10% BM blasts. The analysis confirms the usefulness of IPSS-R for prediction of survival and for better discrimination of high risk patients in subgroups of patients with less advanced disease. Moreover, the results of regression analysis justify the high scoring value of cytogenetic abnormalities used in IPSS-R. SCT represents the only treatment enabling a long-term survival of RAEB-1 patients, nevertheless, our results of SCT were inferior to that achieved in patients with advanced MDS. Thus, more extensive clinical trials validating efficiency of hypomethylating agents and other new drugs in the treatment of RAEB-1 patients are needed.

Disclosures:
No relevant conflicts of interest to declare.