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Background/Aim: Primary mediastinal large B-cell lymphoma (PMLBCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL), whose prognosis has greatly improved since the incorporation of the anti-CD20 monoclonal antibody rituximab into current therapeutic regimens. Evidence, however, on the optimal time interval between consecutive chemoimmunotherapy (CIT) cycles is still scarce. This study aimed to evaluate the efficacy outcomes of the more commonly administered 3-weekly regimens to the biweekly ones in a PMLBCL patients’ population, who were mostly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP-21) or R-CHOP-14. Patients and Methods: We retrospectively studied our cohort of consecutively treated PMLBCL patients, focusing on their treatment density, in order to determine possible differences in treatment outcomes. Results: CIT, in the form of both R-CHOP-21 as well as R-CHOP-14 (or similar regimens), is highly active in PMLBCL, with low rates of early treatment failure. In our cohort of patients, R-CHOP-14 did not result in a meaningful improvement of freedom from progression (FFP) or overall survival (OS). Conclusion: Both R-CHOP-14 and R-CHOP-21 are probably equally effective in PMLBCL, yet further, prospective, randomized studies are warranted to clarify whether dose-dense regimens can be associated with better disease control and long-term results.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

Background R-CHOP can cure approximately 75% of patients with primary mediastinal large B-cell lymphoma (PMLBCL), but prognostic factors have not been sufficiently evaluated yet. R-da- EPOCH is potentially more effective but also more toxic than R-CHOP. Reliable prognostic classification is needed to guide treatment decisions. Materials and Methods We analyzed the impact of clinical prognostic factors on the outcome of 332 PMLBCL patients ≤65 years treated with R-CHOP ± radiotherapy in a multicenter setting in Greece and Cyprus. Results With a median follow-up of 69 months, 5-year freedom from progression (FFP) was 78% and 5-year lymphoma specific survival (LSS) was 89%. On multivariate analysis, extranodal involvement (E/IV) and lactate dehydrogenase (LDH) ≥2 times upper limit of normal (model A) were significantly associated with FFP; E/IV and bulky disease (model B) were associated with LSS. Both models performed better than the International Prognostic Index (IPI) and the age-adjusted IPI by Harrel's C rank parameter and Akaike information criterion. Both models A and B defined high-risk subgroups (13%–27% of patients [pts]) with approximately 19%–23% lymphoma-related mortality. They also defined subgroups composing approximately one-fourth or one-half of the patients, with 11% risk of failure and only 1% or 4% 5-year lymphoma-related mortality. Conclusion The combination of E/IV with either bulky disease or LDH ≥2 times upper limit of normal defined high-risk but not very-high-risk subgroups. More importantly, their absence defined subgroups comprising approximately one-fourth or one-half of the pts, with 11% risk of failure and minimal lymphoma-related mortality, who may not need more intensive treatment such as R-da-EPOCH. Implications for Practice By analyzing the impact of baseline clinical characteristics on outcomes of a large cohort of patients with primary mediastinal large B-cell lymphoma homogeneously treated with R-CHOP with or without radiotherapy, we developed novel prognostic indices which can aid in deciding which patients can be adequately treated with R-CHOP and do not need more intensive regimens such as R-da-EPOCH. The new indices consist of objectively determined characteristics (extranodal disease or stage IV, bulky disease, and markedly elevated serum lactate dehydrogenase), which are readily available from standard initial staging procedures and offer better discrimination compared with established risk scores (International Prognostic Index [IPI] and age-adjusted IPI).

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) represent an important component of therapeutic decision-making. This multi-centric, retrospective, observational study conducted by the treating physicians evaluated the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in 155 patients who received ixazomib via early access programs in Greece, the UK, and the Czech Republic. Median age was 68 years; 17% had an Eastern Cooperative Oncology Group performance status ≥ 2; median number of prior therapies was 1 (range 1–7); 91%, 47%, and 17% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Median duration of exposure to ixazomib was 9.6 months. Overall response rate was 74%, including 35% very good partial response or better (16% complete response). Median progression-free survival (PFS) was 27.6 months (27.6 and 19.9 months in patients with 1 or > 1 prior lines, respectively). IRd treatment for ≥ 6 months was associated with longer PFS (hazard ratio 0.06). Fourteen patients (9%) discontinued IRd due to adverse events/toxicity in the absence of disease progression. Peripheral neuropathy was reported in 35% of patients (3% grades 3–4). These findings support the results of the phase III TOURMALINE-MM1 trial in a broader real-world RRMM population.

Introduction: Carfilzomib is a second-generation irreversible proteasome inhibitor that has been shown to improve overall survival in patients with relapsed and/or refractory multiple myeloma (RRMM). Carfilzomib may exert cardiovascular adverse events (CVAEs), although related mechanisms, prognostic markers and precipitating factors have not been fully characterized. In the prospective randomized phase 3 CANDOR study, comparing daratumumab in combination with carfilzomib and dexamethasone (DaraKd) versus Kd alone, a lower rate of cardiac failure events was observed in the DaraKd arm. The aim of this study was to assess whether treatment with daratumumab may ameliorate carfilzomib-related cardiovascular toxicity. Patients and Methods: This is an ongoing, prospective, observational study on the effects of Kd with or without daratumumab on cardiac function of patients with RRMM. All patients attended an initial visit, which included recording of medical history and cardiotoxicity risk factors (age ≥65 years, obesity, smoking, hypertension, hypercholesterolemia, diabetes mellitus, previous anthracycline use, previous chest or mediastinum radiotherapy and current myocardial disease). At baseline, cardiac ultrasound was performed and images were acquired for standard echocardiographic analysis and for speckle tracking offline analysis. As in ENDEAVOR study, carfilzomib was administered at 20 mg/m2 on days 1 (C1D1) and 2 (C1D2) of cycle 1 and at 56 mg/m2 thereafter, with dexamethasone 40 mg on days 1, 8 & 15 of 28-day cycles (Kd regimen). In the DaraKd regimen, daratumumab was administered at a weekly dose of 16 mg/kg, iv, for cycles 1-2, every 2 weeks for cycles 3-6 and every 4 weeks thereafter, while Kd was given at the dose described previously. A follow-up cardiac ultrasound study, as described above, was performed on the last day of cycle 6 (C6D16) or earlier if carfilzomib interruption was indicated. Patients were followed for a median of 10 months for carfilzomib-related CVAEs [hypertension (HTN), heart failure (HF) and acute coronary syndrome (ACS)]. Results: In this preliminary report, we evaluated 25 patients with relapsed or refractory MM who received either DaraKd or Kd in the everyday clinical practice; 11 patients received DaraKd and 14 received Kd. Patients' mean (±SD) age was 67.8±7.6 years and 60% were men. The two treatment groups did not significantly differ in baseline characteristics including age, gender and prevalence of hypertension, hyperlipidemia, smoking, diabetes mellitus and cardiovascular disease (p>0.1 for all). In the DaraKd group, we did not observe any significant change of markers of left and right ventricular systolic function; however, these markers deteriorated in the Kd group. Specifically, in the Kd group, among left ventricular (LV) systolic function markers, average LV ejection fraction (LVEF) decreased from 59.6±4.8 to 56.6±5.4% (p=0.026) and LV global longitudinal strain (GLS) from -22.5±2.9 to -19.4±3.1 (p=0.007). Similarly, among right ventricular (RV) function markers, tricuspid annular plane systolic excursion (TAPSE) decreased from 23.8±3.6 to 20.4±2.8 mm (p=0.020) and RV free wall longitudinal strain from -31.9±3.4 to -28.2±4.3 (p=0.012). A significant group interaction (p Conclusion: The combination of daratumumab with Kd is associated with preserved post-treatment cardiac systolic function as compared to the Kd regimen in patients with RRMM, who had received 1-3 prior lines of therapy. This was associated with a lower CVAE rate, even in this small group of patients. The clinical significance and the mechanisms mediating this possible protective cardiovascular action of daratumumab merits further investigation, given the high activity of DaraKd in patients with relapsed or refractory MM. Disclosures Terpos: Amgen: Honoraria, Research Funding; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Other: travel expenses , Research Funding; Celgene: Honoraria; Sanofi: Honoraria; BMS: Honoraria. Stamatelopoulos:Amgen: Honoraria, Research Funding. Gavriatopoulou:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Dimopoulos:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau. Kastritis:Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding.

We have studied the efficacy and the prognostic impact of novel agents in 50 primary plasma cell leukemia (pPCL) patients registered in our database. Eighty percent of patients were treated upfront with novel agent-based combinations; 40% underwent autologous stem cell transplantation (ASCT). Objective response rate was 76; 38% achieved at least very good partial response (≥vgPR) and this correlated significantly with bortezomib-based therapy plus ASCT. At the time of evaluation, 40 patients had died. Early mortality rate (≤1 month) was 6%. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 18 months respectively, both significantly longer in patients treated with bortezomib-based therapy + ASCT vs. others (PFS: 18 vs. 9 months; p = 0.004, OS: 48 vs. 14 months; p = 0.007). Bortezomib-based therapy + ASCT predicted for OS in univariate analysis. In multivariate analysis, achievement of ≥vgPR and LDH ≥ 300 U/L were significant predictors for OS. These real-world data, based on one of the largest reported national multicenter series of pPCL patients treated mostly with novel agents support that, among the currently approved induction therapies, bortezomib-based regimens are highly effective and reduce the rate of early mortality whereas in combination with ASCT consolidation they prolong OS.

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary plasma cell tumors. The treatment of choice is local radiotherapy (R/T) ± surgical excision. The role of adjuvant chemotherapy (C/T) or novel agents (NA) is uncertain. Data related to prognostic factors are inconclusive. Herein, we describe the clinical features, survival and prognosis of 97 consecutive patients, 65 with bone SP (SBP), and 32 with extramedullary SP (SEP), diagnosed and treated in 12 Greek Myeloma Centers. Objective response rate (≥PR) and complete response (CR) was 91.8% and 61.9%, respectively, and did not differ between the 2 groups. Overall, 38 patients relapsed or progressed to multiple myeloma (MM). After a median follow-up of 60 months, 5 and 10-year overall survival (OS) probability was 92% and 89% in SEP and 86% and 69% in SBP, respectively (P = 0.2). The 5- and 10-year MM-free survival (MMFS) probability was 90% and 70% for patients with SEP vs. 59% and 50% for patients with SBP, respectively (P = 0.054). Overall, the 5- and 10-year OS probability, plasmacytoma relapse-free survival (PRFS), progression-free survival and MMFS was 84% and 78%, 72% and 58%, 58% and 43%, and 70% and 59%, respectively. In the multivariate analysis, prolonged PRFS and young age were positive predictors of OS. Achievement of CR was the only positive predictor of PRFS. Immunoparesis was the only negative predictor of progression to MM. The addition of C/T or NA-based treatment increased toxicity without offering any survival advantage over R/T. Am. J. Hematol. 89:803–808, 2014. © 2014 Wiley Periodicals, Inc.

Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27 864 patients with haematological malignancies vs. 967 of 1 158 018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib-based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL-pPCL and 17 with secondary PCL-sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR-group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow-up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow-up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity.

OBJECTIVE: To investigate the effects of short term atorvastatin treatment on forearm vasodilatory response to reactive hyperaemia (RH%) and on components of the thrombosis-fibrinolysis system (antithrombin III, proteins and S, factors V and VII, von Willebrand factor, tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI-1)) in patients with heart failure. PATIENTS AND METHODS: 35 patients with heart failure were enrolled in this study; 17 patients received atorvastatin 10 mg/day and 18 patients received no statin for four weeks. Forearm blood flow (FBF) was measured by venous occlusion strain gauge plethysmography. RH% and forearm vasodilatory response to nitrate were defined as the percentage change of FBF from rest to the maximum flow during reactive hyperaemia and after nitrate administration, respectively. Plasma concentrations of antithrombin III, protein C, protein S, factor V, factor VII, von Willebrand factor, tPA, and PAI-1 were determined before and after treatment. RESULTS: Maximum hyperaemic FBF remained unchanged in both groups. Baseline FBF was slightly but not significantly decreased in the atorvastatin treated group. RH% was significantly increased only in the atorvastatin treated group, from mean (SD) 42.44 (18.9)% to 83.7 (36.1)% (p < 0.01). Plasma concentrations of antithrombin III (from mean (SD) 81.7 (11.37)% to 73.5 (13.8)%), protein C (from mean (SD) 88.3 (26.9)% to 63.9 (25.0)%), factor V (from mean (SD) 126.2 (33.4)% to 94.9 (29.8)%), tPA (from median (25th-75th percentile) 11.68 (8.60-20.95) ng/ml to 10.30 (8.65-15.12) ng/ml), and PAI-1 (from median (25th-75th percentile) 3.10 (2.15-4.40) IU/l to 1.90 (0.75-3.0) IU/l) were significantly decreased in the atorvastatin treated group (p < 0.05) but not in the control group. Plasma concentrations of von Willebrand factor, factor VII, and protein S remained unaffected in both groups. CONCLUSION: Atorvastatin did not change the maximum hyperaemic flow, although it decreased plasma concentrations of antithrombin III, protein C, factor V, tPA, and PAI-1 in patients with heart failure. Therefore, short term treatment with atorvastatin may affect the expression of both endothelium and liver derived components of the thrombosis-fibrinolysis system in patients with heart failure.

OBJECTIVE—To examine the effect of vitamin C on forearm vasodilatory response to reactive hyperemia and on plasma level of plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA), antithrombin III (ATIII), proteins C and S, and factors V (fV) and VII (fVII) in patients with both type 2 diabetes and CAD. RESEARCH DESIGN AND METHODS—A total of 39 patients with type 2 diabetes and CAD were divided into two groups and received vitamin C (2 g/day) or no antioxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography at baseline and after treatment. Forearm vasodilatory response to reactive hyperemia (RH%) or nitrate (NTG%) was defined as the percent change of flow from baseline to the maximum flow during reactive hyperemia or after administration of nitrate, respectively. Biochemical markers were determined by enzyme-linked immunosorbent assay (ELISA) or other standard methods. RESULTS—RH% was significantly increased after treatment with vitamin C (from 62.4 ± 7.2 to 83.1 ± 9.3%, P = 0.024) but remained unaffected in the control group. Vitamin C decreased plasma levels of fV (from 143 ± 5.4 to 123 ± 6.03%, P = 0.038), vWF (from 133.5 ± 14.5 to 109.5 ± 11.4%, P = 0.016), and tPA (from 12.3 ± 0.99 to 8.40 ± 0.60 ng/ml, P = 0.001), whereas these levels remained unaffected in the control group. The changes in RH%, vWF, and tPA were significantly greater (P = 0.028, 0.036, and 0.007, respectively) in the vitamin C-treated group than in the control group. Levels of ATIII, proteins S and C, fVII, and PAI-1 remained unchanged in all groups. CONCLUSIONS—Short-term treatment with high doses of vitamin C improved RH% and decreased plasma levels of tPA and vWF in patients with type 2 diabetes and CAD.

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 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.

Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly.

BACKGROUND: Proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) are important mediators of immune response, associated with endothelial dysfunction in patients with coronary artery disease (CAD) or heart failure. We compared endothelial function and levels of IL-6 and TNF-alpha between patients with ischemic heart failure, dilated cardiomyopathy, CAD and healthy controls. METHODS: The population consisted of 20 patients with dilated cardiomyopathy, 48 patients with ischemic cardiomyopathy, 26 patients with CAD and normal left ventricle function and 14 healthy controls. Forearm blood flow was measured using venous occlusion strain gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate were considered as indexes of endothelium-dependent and endothelium-independent dilation, respectively. RESULTS: Levels of IL-6 were significantly higher in ischemic cardiomyopathy compared to CAD patients (P

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary plasma cell tumors. The treatment of choice is local radiotherapy (R/T) ± surgical excision. The role of adjuvant chemotherapy (C/T) or novel agents (NA) is uncertain. Data related to prognostic factors are inconclusive. Herein, we describe the clinical features, survival and prognosis of 97 consecutive patients, 65 with bone SP (SBP), and 32 with extramedullary SP (SEP), diagnosed and treated in 12 Greek Myeloma Centers. Objective response rate (≥PR) and complete response (CR) was 91.8% and 61.9%, respectively, and did not differ between the 2 groups. Overall, 38 patients relapsed or progressed to multiple myeloma (MM). After a median follow-up of 60 months, 5 and 10-year overall survival (OS) probability was 92% and 89% in SEP and 86% and 69% in SBP, respectively (P = 0.2). The 5- and 10-year MM-free survival (MMFS) probability was 90% and 70% for patients with SEP vs. 59% and 50% for patients with SBP, respectively (P = 0.054). Overall, the 5- and 10-year OS probability, plasmacytoma relapse-free survival (PRFS), progression-free survival and MMFS was 84% and 78%, 72% and 58%, 58% and 43%, and 70% and 59%, respectively. In the multivariate analysis, prolonged PRFS and young age were positive predictors of OS. Achievement of CR was the only positive predictor of PRFS. Immunoparesis was the only negative predictor of progression to MM. The addition of C/T or NA-based treatment increased toxicity without offering any survival advantage over R/T.

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib-based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL-pPCL and 17 with secondary PCL-sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR-group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow-up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow-up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity.

Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the “real world” (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (≥PR (partial response)) rate was 77.4 % (complete response (CR), 20.2 %). Median time to first and best response was 2 and 5 months, respectively. Median time to CR when RD was given as 2nd or >2nd-line treatment at 4 and 11 months, respectively. Quality of response was independent of previous lines of therapies or previous exposure to thalidomide or bortezomib. Median duration of response was 34.4 months, and it was higher in patients who received RD until progression (not reached versus 19 months, p < 0.001). Improvement of humoral immunity occurred in 60 % of responders (p < 0.001) and in the majority of patients who achieved stable disease. Adverse events were reported in 68.9 % of patients (myelosuppression in 49.4 %) and 12.7 % of patients needed hospitalization. Peripheral neuropathy was observed only in 2.5 % of patients and deep vein thrombosis in 5.7 %. Dose reductions were needed in 31 % of patients and permanent discontinuation in 38.9 %. Median time to treatment discontinuation was 16.8 months. Performance status (PS) and initial lenalidomide dose predicted for treatment discontinuation. Extra-medullary relapses occurred in 3.8 % of patients. Our study confirms that RD is effective and safe in RRMM in the RW; it produces durable responses especially in patients who continue on treatment till progression and improves humoral immunity even in patients with stable disease.

Primary plasma cell leukemia (pPCL) is an aggressive plasma cell disorder with poor outcome. We and others have previously demonstrated in a limited number of pPCL patients that novel agents and mainly bortezomib-based regimens (BBR) improve response rates and survival; in addition, two recent prospective studies have confirmed the efficacy of lenalidomide-dexamethasone and BBR respectively, followed by autologous transplantation (ASCT) in pPCL; however, the prognostic impact of the induction therapy was not evaluated in both studies. Herein, we explored the clinical characteristics and the impact of current treatments and biological markers on the outcome of an extended cohort of primary PCL (pPCL) patients treated upfront with novel agents, outside clinical trials. We analyzed the medical records of 50 patients with pPCL (M/F: 25:25; median age 65.5 years, range: 32-86 years; IgG: 19, IgA: 9, light-chain only: 14, IgD: 2, non-secretory: 6; ISS1: 5, ISS2: 16, ISS3: 29) out of 2711 myeloma patients (1.8%), registered in the Greek Myeloma study group database, between 2000-2015. Eastern Cooperative Group (ECOG) performance status was ≥2 in 52% of patients; 77% of patients presented with lytic bone disease and 11% with bone or soft tissue palsmacytomas. Bence-Jones protein was present in 68% of patients; 53% of patients had abnormal lactate dehydrogenase (LDH); 28% had hypercalcemia and 68% had hemoglobin After a median follow up of 61 months (95% CI: 34.5-87.4), 38 (76%) patients have died (disease progression: 18, infection: 16, other causes: 4) and 12 patients remain alive. Early mortality (≤1 month) occurred in 3/38 (6%) deceased patients; 31/38 patients who responded in induction treatment progressed; 27/31 patients who progressed received 2nd line treatment (lenalidomide-based: 7, BBR: 16, C/T: 4). Progression-free survival was 12 months (95% CI: 8.5-15.4) and it was marginally longer in patients treated with BBR+ASCT vs. others (18 months vs. 10 months, p=0.07). Median OS was 17 months (95% CI: 13-21 months) and it was double in patients treated with BBR+ASCT compared to others (33 months vs. 16 months); median survival after PCL progression was only 7 months (95% CI: 3-11 months). In the univariate analysis, performance status, LDH, induction treatment with BBR, or treatment with BBR+ASCT and quality of response (≥vgPR vs. These real-world data, based on the largest reported national multicenter series of pPCL patients to-date, support that treatment with BBR plus ASCT is the best currently available option that offers deep and durable responses and reduces early mortality in this setting. Quality of response and high LDH were the strongest independent prognostic factors for OS. We conclude that pPCL requires an aggressive upfront therapeutic approach with a bortezomib-based regimen followed by ASCT that would lead to maximum response and eventually to prolonged OS. Disclosures Katodritou: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Genesis: Honoraria, Research Funding; Takeda: Consultancy, Honoraria. Terpos:Celgene: Honoraria; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Genesis: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria. Delimpasi:Janssen: Honoraria; Genesis: Honoraria; Amgen: Honoraria. Kotsopoulou:Genesis: Honoraria. Kyrtsonis:Genesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Symeonidis:Roche: Honoraria; Amgen: Honoraria; Takeda: Consultancy, Honoraria; Genesis: Honoraria. Kastritis:Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Genesis: Consultancy, Honoraria. Dimopoulos:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: 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; Genesis: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

BACKBGROUND: Bing-Neel syndrome (BNS) is an extremely rare neurologic complication of Waldenström macroglobulinemia (WM) that was first described in 1936 by Jens Bing and Axel Valdemar Neel. It is associated with central nervous system infiltration by neoplastic lymphoplasmacytoid and plasma cells with or without cerebrospinal fluid (CSF) hyperglobulinemia. Herein we report one case of a BNS, presented with central nervous system infiltration at diagnosis. We discuss its epidemiology, presentation, diagnosis and treatment. CASE PERESENTATION A 65-year-old man, was admitted to our hospital with no previous medical history presenting episodes of confusion, slurred speech, headache, fatigue, ataxia and memory problems. Neurological examination revealed left hemiparesis and abnormal pupillary response; normal cranial nerve III, IV, VI examination; Bell's palsy present characterized by left-sided facial droop, pathological Barre Test of the left upper and lower limb and pathological Babinski's sign left; the assessment of the sensory neuron responses did not reveal any findings; the muscular mass was hypotonic and hypotrophic. Initial investigations revealed a normal CBC; biochemical investigations were within normal ranges; thyroid investigation was normal; immunology investigations: IgG 3,02 g/L, IgA Examination of the cerebrospinal fluid (CSF) showed an decrease of the CSF protein ( Neuro-imaging included a brain CT which showed a pathological density area in the left frontal lobe and right occipital area. A later both MRI brain and Magnetic resonance spectroscopy displayed pathological intensity signals in the same areas revealing a tumoral form of BNS. The bone marrow biopsy revealed the presence of a lymphoplasmacytoid and plasma cells infiltration ~50-55% and monoclonal CIgM(κ) (Waldenström macroglobulinemia - WHO 2008) Once the diagnosis was confirmed our patient underwent first line treatment with five cycles of rituximab 500mg/m2 and methotraxate 3.5gr/m2 repeated every 15 days combined with intrathecal chemotherapy with cytarabine 40mg, dexamethasone 4mg and methotrexate 12.5mg repeated every second week. Partial remission confirmed by MRI was obtained after 5 cycles of chemotherapy, the patient improved all his neurological manifestations and his IgM levels decrised to normal. The patient then initiated chemotherapy regimen with cytarabin (4 doses of 2 g/m2). However, very fast, after the first two cycles the disease progressed and he was admitted to our hospital presenting episodes of confusion, slurred speech, ataxia and memory problems. Progressive disease was also comfirmed by an MRI. The fact that the neoplastic cells in Waldenstrom's macroglobulinemia originate from immature lymphocytes suggests that they are sensitive to irradiation therapy. Therefore, cranial radiation therapy was then started combined with rituximab and intrathecal chemotherapy. His neurological complications resided fast. Partial remission was confirmed by MRI. Nine months after diagnosis the patient is in partial remission receiving treatment with rituximab and intrathecal chemotherapy. CONCLUSION Bing-Neel syndrome is an extremely rare complication of Waldenström's macroglobulinaemia with only a few such cases reported to date. Identifying such patients is a clinical challenge, especially when a patient is presented without a known history of WM. Taking in consideration the severe prognosis of BNS and since there is still no consensus on the treatment of BNS the most difficult decisions to make are the ones related to the best therapeutic approach and the best suitable chemotherapy regimen. Although the follow-up period in our case is not long enough to confirm the efficacy of chemotherapy and irradiation therapy, it is nevertheless a valuable asset to the very few reported cases (less than 50) and such clinical experience when reported could allow us to determine a potential cure to this poor prognosis syndrome. Disclosures Kyrtsonis: Genesis: Honoraria; Millenium: Research Funding; Lilly: Research Funding; Amgen: Research Funding.

BACKGROUND: Lipid-lowering agents are known to reduce long-term mortality in patients with stable angina or multiple risk factors. However, the effects of lipid-lowering treatment on inflammatory process during and immediately after the acute phase of unstable angina remain unclear. In this study we assessed the effects of low-dose atorvastatin treatment, on inflammatory process in patients admitted for unstable angina with low cholesterol level. METHODS: Forty-seven normocholesterolemic patients with unstable angina were randomized into two groups, and received atorvastatin 10 mg/day (n = 24) or no statin (n = 23) for 6 weeks. Circulating levels of inteleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha) and soluble vascular cell adhesion molecule (sVCAM-1) were measured by their admission, and at the 1st and 6th week of the study. RESULTS: Serum levels of MCP-1 and sVCAM-1 were significantly increased in the control group (p < 0.05) while remained unaffected in the atorvastatin-treated group six weeks after admission. However, IL-6 and TNF-alpha levels were similarly decreased in both atorvastatin-treated and control groups. CONCLUSION: Low-dose atorvastatin treatment modifies inflammatory process in patients with unstable angina and low cholesterol level, an effect seen at 6 weeks but not 1 week after admission.

BACKGROUND: Unstable coronary syndromes are characterised by increased inflammatory process and endothelial activation. However, the underlying mechanisms of the acute coronary syndromes are still obscure. We evaluated the differences of inflammatory and thrombotic markers, at the acute phase of unstable angina (UA) and acute myocardial infarction (AMI). METHODS: The population of the study consisted of 216 subjects: 136 patients with UA, 57 patients with AMI and 23 healthy controls. Blood samples were taken by their admission to the hospital. Inflammatory and thrombotic markers were measured by ELISA. RESULTS: Patients with UA had significantly higher levels of interleukin-6 (IL-6), soluble vascular cells adhesion molecule (sVCAM-1) and von Willebrand factor (vWF) (p

Purpose of the study was to investigate whether short-term atorvastatin treatment improves endothelial function and affects inflammatory process in patients with heart failure (HF) and normal cholesterol levels. HF is characterized by endothelial dysfunction and increased inflammatory process, while statins restore endothelial function having also anti-inflammatory effects in hypercholesterolemic patients. We investigated the effect of 4-week atorvastatin treatment (10 mg/day) on endothelial function and inflammatory markers in patients with HF and cholesterol levels

The Greek Registry of Myelofibrosis (MF) is held under the auspices of the Acute Leukemias and Myeloproliferative Neoplasms Study Group of the Hellenic Society of Hematology. The preliminary results after two years of retrospective data collection are presented. The total number of patients included is 226, from 10 Greek sites; the initial diagnosis was made between 1975 and 2013. The male to female ratio was 1.66. Median age at diagnosis was 69 years (range 25-88). In 26% of patients myelofibrosis was secondary to pre-existing hematological malignancy (essential thrombocythemia in 60%, polycythemia vera in 31%). The most prevalent presenting symptoms as reported by the treating hematologist were related to anemia (48%), enlarged spleen (33%), leukocytosis (18%) or thrombocytosis (16%) in routine blood counts examination and beta-symptoms (14%), followed by thrombocytopenia (7.3%), leukopenia (5.3%), thrombosis (3.4%), hemorrhage (2.4%), erythremia (1.5%). As documented in patient records at diagnosis, median platelet counts (PLT) were 283x109/L, hemoglobin (Hb) 10.3 g/dL, white blood cell counts (WBC) 10.5 x109/L and the spleen was palpable in 86% of patients. According to the International Prognostic Score System (IPSS), patients were categorized as low risk (15.8%), intermediate-1 (32.3%), intermediate-2 (32.3%) and high risk (19.6%). Molecular studies were performed in 77 patients (34% of total) and 69% of them were positive for the JAK2-V617F mutation. The therapeutic strategy in myelofibrosis is dictated by the symptoms present and can be a combination of agents. In the Greek Registry, all but 7% of patients have required treatment. First-line therapy was a single agent in 68% (hydroxyurea 34%, erythropoetin 19%, androgen 11%, interferon 4%, corticosteroids 3%, ruxolitinib 2%) and a drug combination in the remaining 32%. Taking combinations into account, hydroxyurea was given to 41%, erythropoetin to 31%, androgens to 16%, corticosteroids to 8% and anagrelide to 2% of patients. In second-line therapy, combinations were administered to 50% of patients and they included erythropoetin (27%), androgens (22%), hydroxyurea (15%) or corticosteroids (15%); monotherapy with interferon was given to 6% and ruxolitinib to 4% of patients. At any time during the disease course, splenectomy was performed in 5% and spleen irradiation in 12% of patients for symptom relief. Data for secondary malignancies were available in 170 patients. Acute leukemia occurred in 8% and solid tumor in 5% of patients. Survival information is available for 147 patients. Median overall survival was 4.46 years, whereas 5- and 10-year survival rates were 45.3% and 11.5% respectively. The aim of the registry and the subsequent data analysis is to convey the practice of managing the disease. Moreover, useful conclusions can be reached regarding to the patients’ responsiveness to therapy and the parameters that correlate with overall survival and disease progression. Disclosures No relevant conflicts of interest to declare.

Multiple myeloma of the central nervous system (CNSMM) is a rare and severe clinical entity. The efficacy of novel agents in this setting has not been sufficiently explored. Our aim was to describe the incidence, characteristics and outcome of CNSMM in the era of novel agents, to search for prognostic factors of post CNSMM survival and explore the efficacy of novel agent-based combinations (NAC). Data were provided by 8 Centers of the Greek Myeloma Study Group from January 2000 to December 2013. Documentation of CNSMM required: biopsy that proved CNSMM or MRI/CT findings consistent with CNSMM or detection of plasma cells (PCs) and/or monoclonal immunoglobulin (MC) in the cerebrospinal fluid (CSF). Response to CNSMM treatment was defined as improvement/normalization of at least one of the aforementioned variables. Twenty-four (M/F: 10/14; median age: 63.5 years, range 24-97 years) of 3107 newly diagnosed symptomatic MM patients, who were diagnosed in the same centers during the same period of time, developed CNSMM (0.8%); 2 of them were newly diagnosed and 22 had received previous therapies (6/22 had CNS involvement as the sole feature of MM). Fourteen patients had IgG MM, 2 IgA, 3 light chain, 1 IgD and 4 non-secretory MM. The median time to CNSMM diagnosis was 28.5 months (range: 0-98 months). Clinical manifestations included: visual disturbances/diplopia (37%), paresis/paraplegia (29%), lethargy/confusion (25%), headache (16%) and cranial nerve palsy (12%). MRI or CT documentation was available in 20/24 patients and revealed parenchymal lesions (35%), leptomeningeal lesions (10%), direct MM extension (20%), parenchymal/leptomeningeal (10%), parenchymal/direct MM extension (15%) or leptomeningeal/direct MM extension (10%). Diagnostic lumbar puncture was performed in 17 patients and in 10/17 PCs were detected in the CSF (median number of PCs/μL was 172.5/μL, range: 5-2550/μL). LDH and albumin in the CSF was high in all patients, while MC was detected in the CSF of 4 patients. Sixteen patients (67%) had additional extramedullary disease (EMD) or plasma cell leukemia (PCL) prior to CNSMM diagnosis (plasmacytomas: 9 patients, PCL primary/secondary: 3/3 patients, EMD/PCL: 1 patient). Molecular cytogenetics were available in 12/24; 4 patients had high risk cytogenetics. Patients who developed CNSMM after frontline therapy (n=22) had higher LDH at the time of CNS involvement compared to initial MM diagnosis (267 U/L vs 191 U/L; p=0.02). NAC had been given in 17/22 (77%) such patients prior to CNSMM diagnosis (bortezomib-based: 17, IMiD-based: 13, both: 13). The median number of previous MM treatment lines in these patients was 3 (range: 1-5). Treatment of CNSMM included NAC (bortezomib-based 9 and IMiD-based 3 patients), chemotherapy alone (7 patients) and only intrathecal infusions (ITI) with MTX or AraC (3 patients); 7 patients received both systematic therapy and ITI. Additional radiotherapy (RT) was given to 8 patients; one patient underwent ASCT consolidation. Regarding CNSMM response, 10/22 treated patients had improvement or normalization of initial CNS findings and 6 of them relapsed. At the time of evaluation, 2 patients were alive and 22 patients had died (MM progression: 13, sepsis: 6, cerebral hemorrhage: 2, leishmaniasis: 1 and CNSMM progression: 1). The median post CNSMM survival was 3 months (95% CI: 1.9-4.1). The median post CNSMM survival for patients treated with NAC vs. others was 4 (95% CI: 0-8.6) vs. 2 months (95% CI: 0.7-3.3), respectively (p>0.05). Additional RT did not improve survival (p>0.05). In the cox regression analysis, prior treatment with NAC and presence of EMD/PCL prior to CNSMM diagnosis marginally predicted for shorter post CNSMM survival (p=0.05 and 0.068, HzR: 3.03 and 2.57, respectively). The median post CNSMM survival for previously NAC-exposed patients was 2 months (95% CI: 1-2.9) vs. 6 months (95% CI: 0.8-11) for NAC-naive patients (p=0.03), while that of patients with prior EMD/PCL was 2 months (95% CI: 1.3-2.6) vs. 8 months (95% CI: 0-18) of the others (p=0.06). In the era of novel agents the incidence of CNSMM remains low, but yet outcome is extremely poor. In our study, treatment with NAC ± RT and ITI did not offer any survival advantage. Treatment with NAC and presence of EMD/PCL prior to CNSMM diagnosis seems to predict for shorter post CNSMM survival. Patients with EMD/PCL should be monitored more firmly in order to detect early manifestations of CNSMM. Disclosures No relevant conflicts of interest to declare.

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary tumors consisting of monoclonal plasma cells, without evidence of systematic multiple myeloma (MM). The treatment of choice is local radiotherapy (RT) with or without surgical excision (SE). Our aim was to describe the clinical features, the outcome and prognosis of SP patients. Thus, we studied 97 consecutive patients, 65 with solitary bone plasmacytoma (SBP) and 32 with solitary extramedullary plasmacytoma (SEP), (M/F: 66/31, median age: 61 years, range 17-85 years) who were diagnosed and treated in 12 Greek Myeloma Centers; treatment was given according to each center’s local policy. Patients with SBP and SEP did not differ in age, gender, performance status (PS), Hb, CRP, LDH, calcium, beta2-microglobulin, renal function or impairment of humoral immunity (immunoparesis). Patients with SEP presented more often with serum or urinary monoclonal component (p24 vs. ≤24 months had a 10-year OS of 82% vs. 60% (p=0.01). Achievement of CR predicted positively for PRFS. Immunoparesis (n=24) predicted negatively for progression to MM. Chemotherapy including NA had no prognostic impact on OS, PRFS or MMFS. Our study demonstrated that patients with SP enjoy a prolonged OS that is favorably influenced by young age and PRFS. We also confirmed that patients with SBP progress more frequently to MM compared to SEP in the era of novel agents. Radiotherapy with or without SE remains the treatment of choice for SP. The additional use of systematic therapy including novel anti-myeloma agents increases toxicity without improving survival or decreasing the probability of SP relapse or progression to MM. Immunoparesis predicts for progression to MM. Disclosures: No relevant conflicts of interest to declare.

Renal impairment (RI) is a common complication of myeloma and is associated with increased risk of early death. Accurate assessment of glomerular filtration rate (GFR) in patients with myeloma is important for evaluation of renal function, for drug dosing and for prognostic purposes. The method of assessment of RI and calculation of GFR is important since serum creatinine alone underestimates renal dysfunction, especially in patients of advanced age. The MDRD formula has been widely used for the calculation of GFR but the CKD-EPI formula has been increasingly used among nephrologists since 2009 (Levey et al, Ann Intern Med 2009;150:604-12). However, the performance of these two equations for the estimation of GFR and their relative prognostic ability has not been assessed in large numbers of patients with myeloma. Thus, in order to evaluate the prognostic significance of GFR as calculated by two different formulas, the MDRD and the CKD-EPI, we analyzed the data of 1937 newly diagnosed patients with symptomatic myeloma who were treated within the centers of the Greek Myeloma Study Group. The median age of the patients was 66 years (range 20-96 years); 54% were >65 years of age and 23% >75 years of age; 55% were males and 53% had an ECOG performance status ≤1. Anemia (Hb We examined the prognostic significance in univariate analysis per CKD stage for each calculation formula: median survival for patients with CKD stage 1, 2, 3, 4 and 5, according to MDRD formula was 61, 54, 36, 30 and 23 months, respectively (p In conclusion, for the first time we evaluated two different formulas of estimation of GFR, both based on serum creatinine, age and gender, in a large number of patients with symptomatic myeloma and we found that GFR calculated by the CKD-EPI formula reclassifies the stage of renal impairment of about 9% of patients and has better prognostic ability for survival and predictive ability for early death than the MDRD formula. We propose the broad use of CKD-EPI formula for the estimation of GFR in patients with myeloma. Disclosures: Tsatalas: Genesis Hellas: Honoraria.

The Greek Registry of Essential Thrombocythemia (ET) is implemented under the auspices of the Acute Leukemias and Myeloproliferative Neoplasms Study Group of the Hellenic Society of Haematology. Hereby, we present results after four years of retrospective data collection. The total number of patients included is 1078, from 14 Greek sites; ET was diagnosed between 1982 and 2012. The male to female ratio is 1:1.19. Median age at diagnosis is 63 years, median platelet counts (PLT) 826x109/L, hemoglobin (Hb) 13.6 g/dL, white blood cell counts (WBC) 9.4x109/L. The presenting symptoms were a thrombotic event in 6.8%, a hemorrhagic event in 1.5% of patients. In 79.8% of the patients the diagnosis was made after incidental finding of elevated platelet counts on routine laboratory investigation. Molecular studies were performed in 677 patients and 42.8% of them were positive for the JAK2-V617F mutation. The presence of JAK2-V617F mutation (mutant vs wild type allele) was associated with baseline platelet counts (757.5 vs 882 x109/L) and hemoglobin levels (14.4 vs 13.4 g/dL), p800 x109/L), Hb9.5x109/L, or splenomegaly are associated with thrombotic or hemorrhagic events in the past medical history or during the follow-up of ET patients. The only statistically significant difference was observed in the occurrence of thrombosis during the follow up: 10.1% of those with PLT between 600-800 x109/L, 4.5% in PLT800 x109/L. To assess for possible confounders the multivariable logistic regression model was used, with independent variables the PLT at diagnosis, age >60 years, history of thrombosis and first line therapy. The history of thrombosis was the only statistically significant risk factor with odds ratio (OR) 3.9 (p=0.0005), while PLT was not a statistically significant risk factor (OR=2.5, p=0.074). Antiplatelet therapy was offered in 80% of patients (aspirin in 59.1%, clopidogrel in 4.7%, and combination therapy in 6.5%); anticoagulants (low molecular weight heparin or warfarin) were given in 2.3%, while the remaining 17.8% of patients did not receive any antithrombotic therapy. During the first six months post diagnosis, 31.6% of patients did not need any cytoreductive therapy. The rest 68.4% of the patients received first line therapy (hydroxyurea 80.6%, anagrelide 11.4% and interferon 5.4%). The response rates were 89.9%, 82.1% and 85.7%, respectively. Second-line therapy was received by 25.8% of the patients (hydroxyurea 23%, anagrelide 44.6%, interferon 9.5%), while the off-label combination of hydroxyurea and anagrelide was administered to 21.2% of the patients. Of the 852 patients treated with hydroxyurea as first line therapy, 12.1% switched to anagrelide and 1.2% to interferon. Of those initially treated with anagrelide, 27.6% switched to hydroxyurea and 8.2% to interferon. During the follow up phase, secondary solid tumor occurred in 4% and hematological malignancy in 2.7% of the patients. The aim of the registry and the subsequent data analysis is to convey the practice of managing the disease. Moreover, useful conclusions can be reached regarding to the patients’ responsiveness to therapy and the minimization of thrombotic and hemorrhagic adverse events. Disclosures: Spanoudakis: Genesis Hellas: Honoraria. Kotsianidis:Genesis Hellas: Honoraria, Research Funding.