Abstract: The detection of concurrent JAK2V617F and BCR-ABL mutations is uncommon; an incidence of 2.5% is reported in the literature. Scarce data indicate that the coexistence of JAK2V617F mutation and BCR-ABL translocation may denote an adverse prognostic factor for CML. Recently, the occurrence of novel Calreticulin (CALR) mutations in JAK2/MPL unmutated ET or PMF was reported. To our knowledge, no CALR mutations have been described so far in the context of BCR-ABL positive MPNs. We present 3 cases with molecularly defined diagnosis of another type of MPN in addition to Ph+ CML, including one patient with the novel finding of a CALR mutation in conjunction with the BCR-ABLtranslocation, and we infer a possible mechanism for the emergence of a second MPN clone upon treatment of the initial MPN. A 32 yr old female was diagnosed in 1999 with ET on the basis of marked thrombocytosis in the absence of any underlying cause. She was treated with INF-α and subsequently with anagrelide. Six years later (2005) and while the CBC was normal, cytogenetic and molecular studies disclosed the presence of Ph1 chromosome in 4/20 metaphases and BCR-ABL transcripts (7.2% IS, e15a2). Imatinib was initiated and after 3 months CCyR and MMR were achieved. Due to an increasing platelet count one year later, a trephine biopsy was performed that was compatible with ET. Hydroxyurea (HU) was added to treatment. No JAK2V617F mutation was detected. Fifteen years after the initial presentation, a CALR exon 9 mutation was retrospectively detected in all available samples since diagnosis of CML. The mutant allele burden has remained stable during follow-up, while patient being in MR4 with regard to CML. A 50 yr old woman was diagnosed with PV in 1998. Cytogenetic studies were normal and BCR-ABL was undetectable. JAK2V617F homozygous mutation was present on retrospective testing. A complete hematologic remission was achieved with phlebotomy and HU. Ten years later, re-evaluation due to an increasing WBC disclosed the presence of Ph1 chromosome in 20/20 metaphases and BCR-ABL transcripts (38.4% IS, e15a2). Interestingly, JAK2V617F was not detected. After 4 months of treatment with TKI plus HU, a 2-log BCR-ABL reduction was noted, while JAK2V617F was detected again at a heterozygous state. She received sequentially all 3 first available TKIs due to intolerance. Upon TKI treatment for 9 months, CCyR and MMR were achieved in parallel with emergence of JAK2V617F homozygosity. After achieving MR4 for more than 2 years, the TKI was discontinued and, 3 months later, the patient remains in MR4 with persistent JAK2V617F homozygosity. Due to splenomegaly and increased Hct, treatment with HU is continuously required. An 80 yr old female was diagnosed with chronic phase CML [Ph1+, BCR-ABL (35.5% IS, e15a2)]. She achieved mCyR and 1-log reduction of BCR-ABL levels after 6 months on imatinib. Due to imatinib failure, she was switched to nilotinib at 9 months. Two years after initial diagnosis, while CML was in MMR, an increase in Hct and platelets was noticed and JAK2V617F heterozygosity was detected. Retrospective analysis did not reveal JAK2V617F mutation at diagnosis and on the 3-month sample, while low level of mutant V617F allele was detected on the 6-month sample. Increasing levels of mutant versus wild type allele were detected in all subsequent samples. The patient was treated with phlebotomy, HU and ASA in addition to nilotinib. She died 4 years after initial diagnosis from an unrelated cause while in MR4 for CML and complete hematologic remission for PV. Despite these cases seem to be uncommon, they raise intriguing issues regarding the clonal origins of distinct molecular types of MPNs present in the same patient. They may also challenge the traditional hypothesis of evolution of one type of MPN to another. Instead of perceiving clinical and genetic features of second MPN as simple evolution of a precedent MPN, our cases suggest an alternative explanation based on pre-existence of two different MPN clones. Treatment for the initial MPN, especially with highly-efficient targeted agents (like TKIs for Ph+ CML) may facilitate the emergence of a second clone and vice versa. In conclusion, any divergent manifestations in a patient with MPN may warrant further investigation of genetic markers suggestive of an additional MPN entity. A high level of suspicion for the possibility of coexistence Ph+ and Ph- MPN may result in a more comprehensive treatment approach and optimal outcome. Disclosures No relevant conflicts of interest to declare.

Abstract: Background: The currently used prognostic systems for myelodysplastic syndromes (MDS) do not consider the prognostic role of monocytopenia, although monocytes may participate in the prognosis of the disease as part of the host immunity. Aim: We studied the prognostic significance of monocytopenia in patients with MDS registered in the Hellenic National MDS registry. Methods: We analyzed clinicopathological data from patients with MDS recorded in a large retrospective national registry. Patients with MDS/MPN were excluded, while patients treated with allogeneic hematopoietic cell transplantation were censored for overall survival (OS) and leukemia-free survival (LFS). IBM SPSS statistics, version 23.0 (IBM Corporation, North Castle, NY, USA) was used for the analysis of the results. Kaplan-Meier survival analysis and Cox regression analysis were performed for LFS and OS. Results: The study comprised 1719 patients with MDS per the 2008 WHO classification for MDS. The main characteristics of the patients are shown in Table 1. At the time of data cut-off, 818 patients were deceased and the median follow-up for the remaining 901 patients was 23.0 months. The median absolute monocyte count (AMC) was 0.30 x 109/L (0.00 - 0.99 x 109/L). Patients with excess blasts (RAEB1/2) tended to have lower AMCs (median 0.19 versus 0.32 for patients without excess blasts, p 〈 0.0001) and lower AMCs were found in higher IPSS-R categories (very low, 0.37 x 109/L; low, 0.30 x 109/L; intermediate, 0.25 x 109/L; high, 0.16 x 109/L; very high, 0.20 x 109/L) while there was a highly significant difference between lower risk (very low and low) and higher risk (intermediate, high, very high) MDS (0.33 x 109/L vs 0.21 x 109/L, p 〈 0.0001). In univariate analysis, patients with AMCs below 0.2 x 109/L had a median OS of 34.0 months vs 63.0 months for patients with higher AMCs (p 〈 0.0001) with a hazard ratio (HR) for death of 1.57 (95% CI 1.37 - 1.81, p 〈 0.0001). In a multivariate Cox regression model including hemoglobin below 10 g/dL, absolute neutrophil count (ANC) below 1.0 x 109/L, and platelet count below 100 x 109/L (all of them being prognostic for OS in univariate analysis), monocytopenia retained its prognostic significance (HR, 1.16; 95% CI, 1.00 - 1.36, p=0.049). There was a positive correlation between the AMC and the ANC (Pearson Correlation 0.393, p 〈 0.0001). Nevertheless, in a model comprising of AMC and ANC, both variables were independently correlated to OS. Moreover, in a model including AMC below 0.2 x 109/L, the cytogenetic risk score per the IPSS-R, the number of cytopenias, and bone marrow blasts (categorized per the IPSS-R), no additional prognostic impact was found for AMC (HR, 1.01; 95% CI, 0.86 - 1.17; p=0.957). After stratification per the IPSS-R categories, low AMC was prognostic for low OS only in patients with low IPSS-R (median OS, 57 months for patients with low AMC vs 75 months for those with high AMC, p=0.039), but there was no additional prognostic impact after multivariate analysis. Moreover, AMC was prognostic for LFS, since patients with low AMCs ( 〈 0.2 x109/L) had a median LFS of 57.0 months, while the median LFS for patients with higher AMCs was not reached (HR, 2.47, 95% CI, 2.01 - 2.47, p 〈 0.0001). In a Cox regression model including the above stated factors (cytopenias, bone marrow blasts, cytogenetic risk, and AMC), AMC retained its prognostic significance for LFS (HR, 1.27; 95% CI, 1.02 - 1.58; p=0.031). In a subgroup of 162 patients treated with hypomethylating agents (HMAs), monocytopenia was not predictive or response to treatment, but low AMC was correlated to a shorter median progression free survival (27.0 months vs not reached for patients with higher AMC, p=0.001). This correlation was not translated into a survival benefit (survival after HMA initiation, 27.0 vs 28.0 months respectively, log rank p=0.213). Conclusions: Based on a large patient cohort, we found that patients with MDS with excess blasts as well as higher risk patients per the IPSS-R have low AMCs. Moreover, we showed that low AMCs are prognostic of lower OS in univariate analysis and of lower LFS in both univariate and multivariate analysis, highlighting a possible pathogenetic role for AMCs in MDS. Further analysis is needed to define the exact prognostic role of AMC in MDS. Disclosures Pappa: Amgen: Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene / GenesisPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Research Funding; Abbvie: Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kotsianidis:Celgene: Research Funding. Symeonidis:MSD: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Tekeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Vassilakopoulos:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; WinMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene / GenesisPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract: Introduction: Less than 5% of patients with MDS present with thrombocytopenia as an isolated abnormality (MDS-IT). There have been few systematic studies on MDS-IT and data regarding its course and prognosis are conflicting. Previous studies have defined MDS-IT based on the IPSS thresholds (Hb ≥10 g/dL; ANC ≥1.8×10 9/L; PLT & lt;100×10 9/L). However, these were developed for prognostic, not diagnostic purposes which means that mild anemia and/or neutropenia might be present concomitantly with "isolated" thrombocytopenia. We aimed to investigate the characteristics, overall survival (OS), and leukemia-free survival (LFS) of patients with MDS-IT. Methods: We identified patients who had PLT & lt;150 ×10 9/L, Hb & gt;13 g/dL (men) or & gt;12 g/dL (women), and ANC ≥1.8 ×10 9/L, registered in the Hellenic National Registry of Myelodysplastic and Hypoplastic Syndromes which includes 2792 patients (analysis cut-off date; July 7, 2016). Patients were divided into 4 groups: group 1 had PLT 149-100 ×10 9/L; group 2, 99-50 ×10 9/L; group 3, & lt;50 ×10 9/L; and group 4, & lt;25 ×10 9/L. We also collected data from the Hellenic National ITP Registry which includes 1317 adult patients with ITP. Results: A total of 77 patients (45 men; 32 women) with MDS-IT were identified (2.9% of total MDS cohort). Of these, 28.6% were classified in group 1; 49.4% in group 2; 14.3% in group 3; and 7.8% in group 4. Median PLT count was 87 ×10 9/L (12-139 ×10 9/L), WBC count 4.6 ×10 9/L, and Hb 13.6 g/dL. Bone marrow (BM) blasts ranged from 0-9% (median, 2%). Median follow-up was 51.0 months (41.6-60.4), during which 15 (19.5%) patients died. AML developed in 9 patients (11.7%). Histologically, MDS with multilineage dysplasia (MLD) was seen in 77.6% whereas MDS with excess blasts (EB) and MDS with single lineage dysplasia (SLD) comprised 10.7% and 11.9% of cases, respectively. Most patients (73.5%) had lower-risk MDS on the IPSS-R (i.e. IPSS-R ≤3.5). Of the 59 patients with cytogenetic data, 83.1% had favorable, 13.5% intermediate, and 3.4% poor risk cytogenetics. Most (40) had a normal karyotype followed by isolated del(20q) (6). All patients with del(20q) showed a characteristic set of clinical features: age & gt;60 years, blasts 0-3%, bilineage (erythroid/megakaryocytic) dysplasia, and increased reticulin fibrosis. There were no significant differences between any of the 4 PLT groups regarding age, sex, IPSS-R, cytogenetics, BM blasts, and histology. Median OS was 109 months (95% CI 103-115) and LFS 108 months (101-115). Our results showed no significant difference in OS (P=0.891) and LFS (P=0.871) between the 4 PLT groups. As compared with total MDS cohort, MDS-IT occurred at younger age (64.7 vs. 72.4 years, P & lt;0.001). In a Kaplan-Meier analysis, patients with MDS-IT had markedly longer OS and LFS than patients in the total MDS cohort, even after adjustment for age, sex, IPSS-R, blasts, and PLT (P=0.013 for OS; P=0.017 for LFS) (Figure 1A). There were no differences in the top causes of death: infection was the commonest cause followed by disease progression and cardiovascular disease. Major bleeding comprised 10.3% of deaths in MDS-IT vs. 12.7% in total MDS cohort (P=0.217). In comparing MDS-IT with ITP, the median age at diagnosis was 66.0 years for MDS-IT and 49.0 years for ITP (P & lt;0.001).MDS-IT was uncommon in patients & lt;50 or & gt;80 years. Its incidence reached a peak between the ages of 70-79 years, whereas ITP occurred at a more constant level over time (Figure 1B). Women predominated in ITP and men in MDS-IT (P=0.007). Overall, ITP was associated with more marked thrombocytopenia than MDS-IT (15.0 ×10 9/L vs. 87.0 ×10 9/L) (P & lt;0.001). Median WBC count was higher in ITP (7.6 ×10 9/L vs. 4.6 ×10 9/L; P & lt;0.001). Median Hb was similar in the 2 groups. Patients with ITP had longer OS than MDS-IT (P & lt;0.001). Conclusions: In one of the largest reported series, we conclude that MDS-IT is associated with MDS-MLD, favorable cytogenetics, lower-risk IPSS-R, high survival rate, and a low risk of AML evolution. Our data suggest that the superior prognosis in MDS-IT than general MDS may have intrinsic genomic underpinnings as survival curves remained unchanged after correcting for age, sex, blasts and IPSS-R. Importantly, no significant differences in OS and LFS were noted between the 4 PLT subgroups, suggesting that the degree of thrombocytopenia does not correlate with mortality in MDS-IT. From the diagnostic standpoint, age & lt;50 or & gt;80 years and PLT & lt;25 ×10 9/L favored a diagnosis of ITP over MDS-IT. Figure 1 Figure 1. Disclosures Viniou: Sandoz: Research Funding; Takeda: Research Funding; Novartis: Honoraria, Research Funding; Sanofi: Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Research Funding; Abbvie: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Roche: Research Funding; Astellas: Research Funding; Celgene: Research Funding. Vassilakopoulos: Dr. Reddy's: Research Funding; Amgen: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Other: Travel; AbbVie: Consultancy, Honoraria; Integris: Honoraria; Pfizer: Research Funding; Roche: Consultancy, Honoraria, Other: Travel; Takeda: Consultancy, Honoraria, Other: Travel, Research Funding; Genesis Pharma: Consultancy, Honoraria, Other: Travel; Merck: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Karyopharm: Research Funding; AstraZeneca: Honoraria. Hatzimichael: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Honoraria; Gilead: Honoraria; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Pharmathen- Innovis: Honoraria; GSK: Honoraria; Bristol Myersr Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Symeonidis: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi/Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Demo: Research Funding; MSD: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; WinMedica: Research Funding; Astellas: Consultancy, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GenesisPharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract: Introduction - Aims: Several prognostic scoring systems have been developed for patients with myelodysplastic syndromes (MDS), including the International Prognostic System (IPSS), the WHO Prognostic Scoring System (WPSS) and the Revised IPSS (IPSS-R). We evaluated the prognostic value of the IPSS-R on an independent group of 2,582 Greek patients with MDS, registered in the Hellenic National MDS Registry. The aim of this multicenter study was to validate the IPSS-R as a predictor for leukemia-free survival (LFS) and overall survival (OS), in newly-diagnosed MDS patients and to compare its prognostic significance with that of IPSS and WPSS. Moreover, to investigate the predictive value of IPSS-R in association with other recognized prognostic variables, such as patient's age, baseline serum lactate dehydrogenase (LDH), and ferritin concentrations, IPSS, WPSS, Eastern Cooperative Oncology Group (ECOG) performance status, transfusion dependency, and response to first-line treatment. Methods: Clinicopathological data from 2,582 MDS patients, diagnosed between 1/2000 - 1/2015 and registered in the Hellenic National MDS Registry were analyzed. Patients with MDS/MPN were excluded. Data included age, gender, date of diagnosis, clinical characteristics, WHO-2008 classification, laboratory parameters, transfusion dependency, bone marrow aspirate and biopsy morphology, cytogenetic findings, and type of treatment. LFS was calculated from the date of initial diagnosis of MDS until bone marrow blast increased to ≥20% [transformation to acute myeloid leukemia (AML), according to the WHO classification], or last contact. OS was defined as the time from MDS diagnosis to death, or last contact. Patients alive and not having developed AML until last follow-up were censored for OS and LFS, respectively. Kaplan-Meier survival analysis and Cox regression analysis were performed with regard to LFS and OS. Differences between Kaplan-Meier curves were evaluated using the Mantel-Cox (log-rank) test. All significant variables identified by univariate Cox regression analysis and clinical factors important for MDS were used to build the multivariate Cox regression models. Multivariate Cox regression analysis included only those patients for whom the status of all variables was known, and comprised age, serum LDH, and ferritin levels, transfusion dependency, response to first-line treatment, IPSS, WPSS, and IPSS-R. Confidence intervals (CI) were estimated at the 95% level; all tests were two-sided, accepting p 〈 0.05 as indicative of a statistically significant difference. All statistical analyses were performed with the statistical software SPSS (version 21). Results: 1,623 male (62.9%) and 959 female MDS patients with a median age of 74 years at diagnosis were included in the current study. Complete follow-up information was available for 2,376 patients. The estimated median OS was 58 months (95% CI = 52.9 - 63.1 months). For 1,974 patients, data used in the calculation of all three scoring systems were complete, thus allowing risk score calculation and comparison of the three risk assessment systems. Median OS was significantly different in patient subgroups classified according to IPSS, WPSS, and IPSS-R, as shown by the Kaplan-Meier survival analysis (p 〈 0.001). Fig. 1 shows Kaplan-Meier OS curves of MDS patients stratified according to IPSS-R (p 〈 0.001). Moreover, the comparison of the prognostic value of the IPSS, WPSS, and IPSS-R revealed that the IPSS-R was significantly superior to both, WPSS and IPSS (p 〈 0.001 in all cases). Multivariate Cox regression analysis demonstrated that the high prognostic value of IPSS-R, in terms of LFS and OS, was independent of patient's age, serum LDH, and ferritin concentration, ECOG performance status, and transfusion dependency (p 〈 0.001). Interestingly, besides IPSS-R, patient age and transfusion dependency retain their small - yet significant - prognostic impact in the multiparametric models, thus implying that these two parameters could add prognostic value to the IPSS-R. Conclusions: Our data support the notion that all three prognostic scores are very useful predictors for both, LFS and OS in MDS, yet IPSS-R is superior to IPSS and WPSS as a prognostic tool, with regard to OS. Disclosures No relevant conflicts of interest to declare.

Abstract: Introduction The prognosis of patients with myelodysplastic syndromes (MDS) depends on several disease characteristics such as the cytopenias, the percentage of bone marrow blasts, and the cytogenetic profile of the patients. The use of hypomethylating agents (HMAs) has altered the prognosis of patients with higher risk MDS offering a median survival of around 24 months. Nevertheless, the range of survival is wide, with some patients achieving long remissions and high survival rates irrespective of their initial prognostic characteristics. Long-term survivors after 5-azacytidine administration constitute a large group of patients with potentially special characteristics and needs. Aim We analyzed data from a large cohort of patients with MDS treated with 5-azacytidine to describe the hematologic and prognostic characteristics of long-term survivors and compare them to those of patients with shorter survival. Patients and Methods We retrospectively recorded through the Hellenic 5-azacytidine registry the main demographic, hematologic and treatment characteristics of adult patients with MDS treated with 5-azacytidine monotherapy. Patient data from 28 centers meeting the 2008/2016 WHO diagnostic criteria for MDS were recorded during a 7-month period. We defined two groups of long-term survivors based on their survival after initiation of treatment with 5-azacytidine (OST). The first group comprised patients with OST above the third quartile (Q3 or 75th percentile) of the whole group (Q3 group) and the second patients with OST above the 90th percentile of the whole group (P90 group). Correlations were made between long- and short-term survivors for both groups. IBM SPSS statistics, version 23.0 (IBM Corporation, North Castle, NY, USA) was used for the statistical analysis of the results. Results Data from 626 patients was recorded. The Q3 group comprised 157 patients with an OST longer than 24.5 months (median, 43.3 months) and the P90 group 63 patients with an OST longer than 36.4 months (median, 65.7 months). The detailed characteristics of the two groups along with comparisons with the remaining patients with OST below Q3 and P90 respectively are shown in Table 1. Data analysis revealed that the sex, the age, the type of MDS at diagnosis per the 2008/2016 WHO classification, the presence of excess (≥5%) marrow blasts, the number of cytopenias, the hemoglobin, neutrophil and platelet count, and the transfusion needs were not predictive of long-term survival in neither of the groups. On the other hand, the presence of peripheral blood blasts, the karyotype risk, the IPSS, IPSS-R and WPSS classification and response to treatment were predictive of long term survival in both groups (Table 1). Multivariate analysis revealed that response to 5-azacytidine was the strongest determinant of long-term survival (Kaplan Meier, Log Rank, p 〈 0.0001) in a model comprising IPSS, IPSS-R, WPSS and response to treatment. Nevertheless, patients with stable disease were almost equally distributed in the groups of long- and short-term survivors (p=0.795 for the Q3 group and p=0.310 for the P90 group). Discussion The use of HMAs in MDS has increased survival rates, hence long-term survival is now a feasible target when managing such patients. One fourth of the patients of this registry achieved an OST over 24.5 months and 10% over 36.4 months. IPSS, IPSS-R and WPSS are powerful prognostic tools for patients with MDS. Among the prognostic components of IPSS and IPSS-R at diagnosis (cytopenias, bone marrow blast count, karyotype risk), the karyotype risk seems to be the stronger determinant of survival. Nevertheless, among long-term survivors there are patients with adverse prognostic characteristics at diagnosis, whose prognosis is altered by the administration of HMAs. Failure to respond to 5-azacytidine is a major determinant of OST, but stable disease was not correlated to survival in this cohort. This result highlights the importance of continuing treatment with hypomethylating agents in patients not achieving an optimal response (PR, CR, HI), since a significant proportion of them may achieve long survival rates. Further search for new clinical and/or molecular prognostic markers is warranted to identify the prognosis of patients with MDS and define those who would benefit from the use of HMAs or other upcoming treatment choices. Table 1. Table 1. Disclosures No relevant conflicts of interest to declare.