Abstract: Introduction: Clinical trials in patients with high risk myelodysplastic syndromes (MDS) have shown that these patients benefit from the available hypomethylating agents 5-azacytidine and decitabine. The majority of these patients display hypercellular bone marrow, but a small proportion despite the excess of blasts, exhibit marrow hypocellularity ( 〈 30% cellularity). Data are limited for the efficacy and safety of treatment with hypomethylating agents in this patient subgroup. In the present study we examined the effect of bone marrow cellularity in the overall survival in patients with MDS treated with azacitidine. Patients & Methods: This is a retrospective multicenter study from the Hellenic National MDS Registry (EAKMYS) on behalf of the Hellenic MDS Study Group. Between 1.1.2009 and 31.12.2018 a total of 1161 MDS patients who have received treatment with azacytidine have been registered. Complete patient information and follow-up were available for 989 patients, and all these have been included in the final analysis. Statistical analysis was performed and overall survival (OS) was evaluated, using Kaplan-Meier estimates (GraphPad Prism software, CA). A p value less than 0.05 was considered statistically significant. Results: Forty nine patients had a hypocellular bone marrow (hMDS), representing the 4.95% of the whole patient population. Of these patients 39 were men (5.3% of all men included in the study) and 10 were women representing the 2.98% of all women enrolled (male to female ratio 3.9). In the non-hypoplastic group, 750 were men and 358 were women (male to female ratio 2.09). The median age at diagnosis for the hMDS group was 70.8 years, compared to 72.8 years in the non-hypoplastic group. The IPSS-R prognostic risk categorization included 15 hMDS patients in the low group, 9 in the intermediate, 14 in the high and 11 in the very high risk group. Twenty-six patients (53%) of the hMDS group had bone marrow blasts between 10 and 20%, and the remaining 23 (47%) had 5-10% blasts. The patients with hMDS received an average of 10 cycles of azacytidine treatment during the follow-up period (range 2-29 cycles). The outcomes tested were overall survival and progression to AML. The median overall survival of patients with hMDS, following azacytidine treatment start, was not significantly different from the median survival of patients with non-hypoplastic MDS [20 months versus 16 months in the non-hypoplastic group (95% CI of ratio: 0.839 to 1.863). The survival curves were not significantly different between the hMDS and non-hypoplastic MDS group (p=0.32, Figure 1). Progression to AML was also evaluated. Eleven (22.4 %) hMDS patients showed disease progression to AML. Patients with hMDS had significantly prolonged estimated median time to AML transformation, compared to the non-hypoplastic MDS population (31.7 versus 22 months respectively, p 〈 0.001). There were not any major safety issues among patients with hMDS, despite the increased RBC and Platelet transfusion needs. The infectious episodes and the hospitalization courses did not differ significantly between the hMDS and the non-hypoplastic group. Discussion and Conclusive remarks: In this retrospective study, in which a large number of MDS patients was analyzed, we showed that bone marrow cellularity does not affect the outcome in patients treated with azacyitidine. Patients with hMDS show statistically significant slower AML progression compared to non-hypoplastic MDS. Bone marrow cellularity should not be a contraindication for using hypomethylating agents as a therapeutic option, and this type of treatment can be used safely, when indicated, also in patients with hMDS. Disclosures Pappa: Amgen: Research Funding; Gilead: Honoraria, 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; Abbvie: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Vassilakopoulos:Merck: Honoraria; Takeda Pharmaceuticals: 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; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Winmedica: Honoraria; Servier: Membership on an entity's Board of Directors or advisory committees. Symeonidis:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tekeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Celgene: Honoraria, 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; Gilead: 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.

Abstract: A 69-year-old man was admitted to the emergency department with headache and dizziness. He was submitted to brain computed tomography (CT) which showed a tumor in the right cerebellar hemisphere, findings which were subsequently confirmed with magnetic resonance imaging (MRI). He underwent a paramedian suboccipital craniotomy for removal of the mass. Histology confirmed the presence of a hemangiopericytoma. The patient was discharged 5 days postoperatively with improvement in his symptoms. Fifteen days later, he presented with gait difficulties. Clinical examination revealed positive Mingazzini sign on his left side. He was submitted to brain MRI which revealed bilateral subdural hematomas on late subacute stage with mass effect and midline shift caused by the largest on the right. The patient underwent burr hole evacuation of the right subdural hematoma. The postoperative CT showed evacuation of the right chronic subdural hematoma. Two days postoperatively, the patient's symptoms improved.

Abstract: INTRODUCTION: The hypomethylating agents 5-azacitidine (5-AZA) and decitabine are recently considered the most preferable treatment option for patients with intermediate-2 and high-risk myelodysplastic syndromes (MDS), by International Prognostic Scoring System (IPSS). 5-AZA responders experience improved survival both in clinical trials (AZA 001) and in the real-life setting. Thrombocytopenia is a common event in MDS, during the course of the disease; recently, severe thrombocytopenia (≤30,000 platelets/μL) has been suggested as an important factor regarding the survival of MDS patients. In the present study, we examined the potential prognostic significance of severe thrombocytopenia, in intermediate-2- and high-risk MDS patients, being treated with 5-AZA, during the first 3 years of treatment. METHODS: This retrospective study included 850 higher-risk patients (intermediate-2- and high-risk), registered in the the Hellenic MDS Registry, treated with 5-AZA from 2010 to 2018 and were followed up for a time period up to 3 years. Complete patient data were available for 225 patients. Biostatistical analysis performed in this study included Kaplan-Meier survival analysis and Cox regression. The level of statistical significance was set at a probability value of less than 0.050 (P 〈 0.050). RESULTS: The current study included 225 patients (159 male and 66 women) with intermediate-2- or high-risk MDS treated with 5-AZA, with a median age of 74 years (range: 47 - 89). WHO diagnosis included 1 (0.4%) case of RCUD, 8 (3.6%) cases of RCMD, 3 (1.3%) cases of RCMD-RS, 43 (19.1%) cases of RAEB-1, and 170 (75.6%) cases of RAEB-2. According to IPSS, 174 (77.3%) patients were classified in the intermediate-2 risk group and 51 (22.7%) patients in the high-risk group. In addition, according to IPSS-R, 24 (10.7%) patients were categorized in the intermediate risk group, 106 (47.1%) patients in the high-risk group, and 95 (42.2%) patients in the very-high risk group. All patients were evaluated regarding response to 5-AZA treatment. The initial response at 6 months was: complete remission (CR) in 40 (18.4%) patients, partial remission (PR) in 24 (11.1%) patients, hematological improvement (HI) in 35 (16.1%) patients; therefore, the initial overall response rate (CR, PR, and HI) was 45.6%. Stable disease (SD) was achieved by 56 (25.8%) MDS patients, while 62 (28.5%) patients showed progression of disease (PD) or treatment failure. Severe thrombocytopenia was not predictive of response, as shown using logistic regression analysis. However, severe thrombocytopenia predicted poor overall survival (OS) in the first 3 years of treatment with 5-AZA, as shown by the Kaplan-Meier analysis (Figure 1; P=0.016). Regarding AML-free survival, a strong trend was observed for thy unfavorable prognostic role of this severe cytopenia (P=0.096). Univariate Cox regression analysis for OS revealed a statistically significant hazard ratio (HR) of 1.6 for MDS patients with severe thrombocytopenia (HR=1.6, 95% CI=1.08, P=0.019). CONCLUSIONS: Our study showed that severe thrombocytopenia (≤ 30,000 platelets/μL) in intermediate-2- and high-risk MDS patients, treated with 5-AZA, predicts lower OS rates during the first 3 years of treatment. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract: To assess: (i) the prevalence, and clinical and imaging characteristics of immune checkpoint inhibitor (ICI)-induced musculoskeletal immune-related adverse events (ir-AEs) in a prospective manner and (ii) whether serum levels of cytokines associated with the Th1/Th2/Th17 response are differentially expressed in patients with and without musculoskeletal Ir-AEs. Methods All patients treated with ICI who developed musculoskeletal manifestations were referred to the Rheumatology Department, and an MRI of the involved area(s) was performed. Results During the study period, a total of 130 patients were treated with ICIs. Of these, 10 (7.7%) developed ICI-induced Ir-AEs. The median time from ICI treatment since development of symptoms was 2.5 months. Three different patterns of musculoskeletal manifestations were found: (i) prominent joint involvement (n = 3); (ii) prominent ‘periarticular’ involvement (n = 4). These patients had diffuse swelling of the hands, feet or knees. MRI depicted mild synovitis with more prominent myositis and/or fasciitis in the surrounding tissues in all cases; (iii) myofasciitis (n = 3). Clinically, these patients presented with pain in the knee(s)/thigh(s), whereas MRI depicted myofasciitis of the surrounding muscles. Patients with musculoskeletal ir-AEs had significantly higher oncologic response rates compared with patients not exhibiting musculoskeletal ir-AEs (50% vs 12.5%, respectively, P = 0.0016). Cytokine levels associated with a Th1/Th2/Th17 response were similar between patients with and without musculoskeletal ir-AEs. Overall, symptoms were mild/moderate and responded well to treatment, with no need for ICI discontinuation. Conclusion In our cohort, ICI-induced musculoskeletal manifestations developed in 7.7% of patients. Imaging evidence of myofasciitis was found in most patients, indicating that the muscle/fascia is more frequently involved than the synovium.