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Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events (CVAEs). We prospectively investigated the effect of CFZ on endothelial function and associations with CVAEs. Forty-eight patients treated with Kd (CFZ 20/56 mg/m2 and dexamethasone) underwent serial endothelial function evaluation, using brachial artery flow-mediated dilatation (FMD) and 26S proteasome activity (PrA) measurement in PBMCs; patients were followed until disease progression or cycle 6 for a median of 10 months. FMD and PrA decreased acutely after the first dose (p 40% at the end of first cycle was also independently associated with CVAEs (HR = 3.91, 95% CI 1.29–11.83). Kd treatment impairs endothelial function which is associated with PrA inhibition and recovery. Both pre- and posttreatment FMD predicted CFZ-related CVAEs supporting its role as a possible cardiovascular toxicity biomarker.

The regimen of 5-azacytidine for patients with myelodysplastic syndrome (MDS) has remained unchanged since its first approval. Although several modifications have since been made and delays and dose reductions are common especially during the first treatment cycles, there are minimal data on the prognostic effect of these modifications. In this study, based on data from 897 patients with MDS treated with 5-azacytidine recorded in a national registry, the effect of treatment delays and dose reductions on response, transformation to acute myeloid leukaemia, and survival (after 5-azacytidine initiation, OST ) were analysed. Delays during the first two cycles were noted in 150 patients (16·7%) and were found to adversely affect OST independently of the International Prognostic Scoring System score [hazard ratio (HR), 1·368; P = 0·033] or pre-existing neutropenia (HR, 1·42; P = 0·015). In patients achieving a response, delays before response achievement were correlated with its type (complete remission, 2·8 days/cycle; partial remission, 3·3 days/cycle; haematologic improvement, 5·6 days/cycle; P = 0·041), while delays after response achievement did not have any effect on retention of response or survival. Dose reductions were found to have no prognostic impact. Based on our results, treatment delays especially during the first cycles should be avoided, even in neutropenic patients. This strict strategy may be loosened after achieving a favourable response.

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.

Background Hypomethylating agents have altered the prognosis of myelodysplastic syndrome (MDS) so that long-term survival is now a feasible treatment goal. Patients and Methods We analyzed data from patients with MDS treated with 5-azacytidine recorded in the Hellenic 5-azacytidine registry. We divided patients, on the basis of their survival after 5-azacytidine initiation (OST), in groups of long-term survivors (Q3 and P90 group with OST above the third quartile and the 90th percentile of the whole group, respectively) and short-term survivors comprising the remaining patients, and compared the characteristics between the groups. The study included 626 patients, 157 in the Q3 group and 63 in the P90 group. Results Categorization per the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), and World Health Organization–based prognostic scoring system (WPSS) was found to predict long-term survival, while multivariate analysis revealed that response to 5-azacytidine was the strongest predictor of long-term survival. Nevertheless, patients with hematologic improvement (HI) and stable disease (SD) were equally distributed in the groups of short- and long-term survival. Conclusion SD should not be considered a poor treatment response and should not be grouped with failure, while HI offers similar prognosis to SD and thus should not be grouped with complete and partial remission. Patients with SD should continue treatment with 5-azacytidine.

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.

Carfilzomib (CFZ) improves survival in relapsed/refractory multiple myeloma but is associated with cardiovascular adverse events (CVAEs). We prospectively investigated the effect of CFZ on endothelial function and associations with CVAEs. Forty-eight patients treated with Kd (CFZ 20/56 mg/m

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).

Our aims were to identify factors associated with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) in patients with hematological malignancies and evaluate the outcome of the affected patients. Consecutive patients with hematological malignancies who developed PA BSI were identified. Subsequently, two case-control studies were performed to evaluate the risk factors (i) for PA BSI and (ii) for carbapenem resistant (CR) PA BSI. Patients' outcome was evaluated at 28 days after the onset of bacteraemia. A total of 64 patients with PA BSI (45 caused by CS and 19 by CR organisms) and 128 without PA BSI were enrolled. Patients with rapidly fatal disease, steroid use, neutropenia or prior surgery were more likely to develop PA BSI, whereas patients with previous hospitalization and prior use of fluoroquinolones were more likely to develop CR PA BSI. The 28-day mortality rate was 35.9%. Severity of sepsis was the only independent predictor of adverse outcome.

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.

Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) are currently among the most important nosocomial pathogens in many geographic regions. A retrospective study was conducted between 2010 and 2014 in four hospitals located in a high-prevalence area (Athens, Greece) to describe the clinical features, treatment and outcomes of neutropenic patients with haematological diseases complicated with CP-Kp bloodstream infections. A total of 50 patients were identified, including 48 with haematological malignancies and 2 with aplastic anaemia. All patients had neutropenia (

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

e19033 Background: PBL is a very rare condition which constitutes less than 1% of all lymphomas. Due to the uncommon entity of this disease there is a lack of concordance in the characteristics, optimal management, treatment strategies and the associated outcome. Methods: Herein, we retrospectively review 12 consecutive patients initially diagnosed with PBL and also treated at our institution from 2001 to present. Results: The median age of the patients was 49 years old. Eight patients were female and 4 male. The histological type of all 12 patients presented was DLBCL. Ten patients (83%) were presented with Ann Arbor Stage I or II disease. While 2 patients (17%) had stage IV disease, none of them showed bone marrow involvement at their initial diagnosis. The median follow-up after achieving CR was 80 months. Our analysis demonstrated that age less than 47 years, lack of B symptoms, normal LDH level, Stage I or II and female gender were found to be favorable prognostic factors for achieving CR and OS. All 12 patients underwent chemotherapy with most of them (10; 83%) receiving 6 to 8 cycles of the RCHOP regimen. The majority (11; 92%) of them received chemotherapy followed by radiotherapy. After front line chemotherapy followed by radiotherapy most patients (9; 75%) achieved CR. Among the remaining three patients, the one patient died before completing first line chemotherapy due to an infection during chemotherapy-induced neutropenia, the other patient is undergoing autologous stem-cell transplantation due to refractory PBL and the third one achieved CR after he underwent high-dose chemotherapy and autologous stem-cell transplantation due to refractory PBL. Both patients that had refractory disease were male and initially diagnosed with stage IV PBL. The median OS was 100 months. Conclusions: The data from our study supports that most PBL patients have had early stage disease (IE-IIE) on diagnosis which also was the most important favorable prognostic factor. Overall, patients with primary lymphoma involving the bone with DLBCL have an excellent prognosis and only a limited number of patients underwent autologous stem-cell transplantation in order to achieve CR.

In a study of 27,864 patients with haematological malignancies, 40 patients with candidaemia were identified, among whom 21 developed candidaemia while receiving systemic antifungal therapy [breakthrough candidaemia (BTC)]. Demographic, clinical, microbiological and molecular features of these episodes were analysed. Compared with 19 patients with de novo candidaemia, patients with BTC were more likely to have neutropenia (81% vs. 63%), longer median duration of neutropenia (27 days vs. 15 days), hypogammaglobulinaemia (62% vs. 37%) and central venous catheters (CVCs) (86% vs. 68%). The median duration of prior antifungal exposure was 46 days (range 3-108 days). Among the 18 available Candida spp. isolates, 15 (83%) were phenotypically susceptible to the antifungal agent that the patient was receiving. Emergence of resistance was the mechanism leading to BTC in three cases of patients receiving echinocandins. Other possible mechanisms of BTC were (i) elevated (≥2) minimum lethal concentration/minimum inhibitory concentration (MLC/MIC) ratio (reduced ability for a fungicidal agent to kill a fungal pathogen) in all patients receiving amphotericin B and (ii) elevated MLC/MIC ratios in all Candida parapsilosis isolates with MICs≤1 μg/mL to echinocandins. DNA sequencing of the hotspot 1 region of the fks1 and fks2 genes in seven different isolates of C. parapsilosis group demonstrated P660A in Fks1 but no polymorphisms in fks2. In conclusion, mechanisms for BTC in the setting of prolonged neutropenia may be host-based (hypogammaglobulinaemia and CVC) and pathogen-based. CLSI interpretive breakpoints do not reliably predict BTC in patients with haematological malignancies and warrant further investigation.

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.

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.

e13104Background: Isolates of pathogens that are resistant to all, or almost all, commercially available antibiotics are now prevalent worldwide. The increasing frequency of MDR pathogens is concer...