ALBERT

Description: While there have been many discussions on the standard Si pn -diodes, little attention has been paid and confusion still arises on the ideality factor of the radiative recombination current in semiconductor light-emitting diodes (LEDs). In this letter, we theoretically demonstrate and experimentally confirm by using blue and infrared semiconductor LEDs that the ideality factor of the radiative recombination current is unity especially for low-current-density ranges. We utilize the data of internal quantum efficiency measured by the temperature-dependent electroluminescence to separate the radiative current component from the total current.

Description: The influence of renormalization plasma screening on the entanglement fidelity for the elastic electron-atom scattering is investigated in partially ionized dense hydrogen plasmas. The partial wave analysis and effective interaction potential are employed to obtain the scattering entanglement fidelity in dense hydrogen plasmas as functions of the collision energy, the Debye length, and the renormalization parameter. It is found that the renormalization plasma shielding enhances the scattering entanglement fidelity. Hence, we show that the transmission of the quantum information can be increased about 10% due to the renormalization shielding effect in dense hydrogen plasmas. It is also found that the renormalization shielding effect on the entanglement fidelity for the electron-atom collision increases with an increase of the collision energy. In addition, the renormalization shielding function increases with increasing collision energy and saturates to the unity with an increase of the Debye length.

Description: The influence of neutral particle collisions on the spin-channel preference for spin-asymmetry scattering is investigated in dense plasmas. The effective electron-electron interaction potential taking into account the electron-neutral collision effects is employed to obtain the scattering cross sections for the spin-triplet and singlet states and spin-asymmetry scattering parameter. It is found that the electron-neutral collision effect enhances the spin-asymmetry scattering parameter as well as the preference for the spin-singlet scattering channel. It is also shown that the preference for the spin-singlet scattering channel increases with an increase of the thermal energy. In addition, it is found that the angular averaged spin-asymmetry parameter decreases with increasing collision frequency and thermal energy. The variations of the spin-singlet and spin-triplet scattering channels are also discussed.

Description: Background: High-intermediate or high risk in international prognostic index (IPI) has a long-term chance of cure in the range about 50% in patients with diffuse large B cell lymphoma (DLBCL) treated by R-CHOP. These high risk patients should be considered for additional new treatment to standard R-CHOP or investigational approaches in the context of clinical trials that are designed to ensure that potentially curative therapy. Bortezomib inhibits NF-κB activation through proteasome inhibition, providing rationale for its use in cells that constitutively express NF-κB. Non-germinal center B cell (GCB) DLBCL has a worse survival after upfront chemotherapy and is characterized by constitutive activation of the antiapoptotic NF-κB pathway, which can inhibit chemotherapy. There is no study of bortezomib as maintenance therapy after treated with R-CHOP in high risk patients with DLBCL. So we applied additional bortezomib as maintenance therapy in order to assess improving efficacy and survival rates in high risk patients with non-GCB DLBCL who had been confirmed complete response (CR) after treated with R-CHOP. Methods: Patients with newly diagnosed stage II(bulky)-IV DLBCL with high or high intermediate IPI score of 3 to 5, and patients achieving a CR at the end of 6 or 8 cycles of R-CHOP21 were eligible for enrollment. Non-GCB DLBCL according to Hans criteria confirmed by central review was need before enrollment. Bortezomib maintenance treatment was consisted of bortezomib 1.3mg/m2 subcutaneously administration day 1 and day 15 per 28-day cycle with a total of 12 cycles. The primary endpoint was 3-year progression-free survival (PFS). Secondary endpoints were 3-year overall survival (OS), and toxicites. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Results: Fifty-nine patients were enrolled between May 2014 and Oct 2018. The type of Non-GCB DLBCL in all patients was confirmed by the central pathology review. The median age was 65 years (range: 27-86 years), and 60% were 〉 61 years. The baseline clinical features were as follows: female sex, 45.8%; ECOG 〉1, 10.2%; stage II bulky (〉10cm), 6.8%; stage III/IV, 93.2%. At the time of analysis, 29 patients completed 12-cycles of bortezomib maintenance, and 3 patients is ongoing. Seven patients did not finished maintenance therapy due to toxicities (fatigue, atrial flutter, neuropathy, pleural effusion, thrombocytopenia), and withdrawal of informed consent (n=4). Sixteen patients experienced disease progression during bortezomib maintenance treatment. With a median follow-up of 25.1 months, 3-year PFS rate was 56.9% and 3-year OS rate was 86.4% (Figure 1). Toxicity was assessed in 489 cycles of bortezomib maintenance in all 59 patients. There was no treatment-related death and febrile neutropenia. Conclusion: Bortezomib maintenance showed 3-year PFS rate of 56.9% with acceptable toxicities in patients with high risk DLBCL achieving a CR at the end of 6 or 8 cycles of R-CHOP21. Figure 1 Disclosures Kim: Celltrion: Research Funding; Novartis: Research Funding; J + J: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

Description: Introduction In aggressive lymphoma, the prognostic value of FDG-PET/CT is well established to assess the response to therapy and predict long-term outcome. However, there are still many controversies for using PET/CT in indolent non-Hodgkin lymphomas because of the low FDG avidity. Therefore, this study was planned to evaluate the roles of PET/CT in marginal zone lymphoma, which is a representative of indolent lymphoma. Method We retrospectively analyzed the data of 136 patients with advanced stage marginal zone lymphoma from 13 independent institutions between January 2008 and January 2018. All of the enrolled patients had Ann Arbor stage III-IV except some patients with stage II with bulky mass or rapid progression. Patients were treated with 6th or 8th cycles of immunochemotherapy which consisted of R-CVP (Rituximab, cyclophosphamide, vincristine, prednisolone) (90.4%), R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (5.9%), R-B (Rituximab, bendamustine) (3.7%). PET/CT scan was performed at diagnosis, after 2~3 cycles of immunochemotherapy (interim), and at the end of the treatment. Interim PET/CT response was assessed according to Deauville 5-PS (DS) and semi-quantitative assessment based on the rate of reduction in the SUVmax (deltaSUVmax). Results The median age of the patients was 59.5 years (range;28.0~84.0), and 115 patients (84.6%) had stage III-IV. 119 patients (87.5%) had one or more extranodal site involvement, and gastrointestinal tract (25%) was the most commonly involved extranodal site. Fifty-one patients (37.5%) were classified into high risks and 85 patients (62.5%) were with low risks based on IPI. The median SUVmax of the lesion was 4.8 (range; 0.8-23.5) on initial PET/CT. According to Deauville 5-PS in interim PET/CT, 37 patients (27.2%) were defined in score 1, 34 patients (25.0%) in score 2, 31 (22.8%) patients in score 3, 27 patients (19.9%) in score 4, and 7 patients (5.1%) in score 5. The optimal cutoff value for the deltaSUVmax was 59.8 according to the ROC analysis. After median follow up of 35.9 months, performance status, LDH, IPI and interim PET/CT response were significant prognostic factors for progression free survival (PFS) in univariate analysis. Patients who achieved complete metabolic response (DS 1-2) showed significantly longer progression free survival (PFS) than patients with DS 3-5 grade (Figure 1A, 89.3 months vs. 43.9 months, P=0.046). However, the semi-quantitative method using deltaSUVmax did not predict the survival outcome. In regard to post-treatment PET/CT assessment, patients who achieved complete response showed long PFS (Figure 1B, P

Description: Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 WHO classifications of the lymphoid neoplasms, as it was found that features of MEITL differed from those of enteropathy-associated T-cell lymphoma. It is now considered that MEITL is more prevalent in Asia, and almost all cases of intestinal T-cell lymphoma in Asians might be MEITL. To further elucidate the clinicopathologic features of this new disease entity, we carried out a multicenter, retrospective analysis from 9 tertiary institutes in Korea. Patients and methods: A total of 38 patients who were diagnosed with MEITL between 2002 and 2017 from 9 institutes were included in the analysis. Medical records including age, sex, stage, presenting symptoms, laboratory findings, primary sites, and treatment outcomes were collected. The histopathologic diagnoses were centrally-reviewed by experienced lymphoma histopathologists. The primary end-point of the analysis was overall survival (OS). Results: The median age of the patients was 59 (range, 20 - 84) and 27 patients (71.1%) were male. None of the patients had prior history of Celiac disease. Thirty one patients (81.5%) were stage I-II by the Ann-Arbor classifications, and 28 patients (73.7%) were stage I-II1&2 by the Lugano classifications. The most frequent site of involvement was jejunum (N = 20) followed by ileum (N = 17), and 11 patients had multiple site involvement. In line with the previous reports, most cases expressed CD8 (77.1%) and CD56 (92.1%), and did not expressed CD30 (5.3%), and EBER (6.9%). T-cell intracellular antigen was positive in 14 out of 17 cases (82.4%). The median progression-free survival was 6.9 months (95% CI 4.2 - 9.6), and the median OS was 14.8 months (3.0 - 26.6). Thirty one patients (81.6%) received surgery, and 34 patients (89.5%) received chemotherapy. CHOP (N = 28) was the most frequently used regimen followed by CHOEP (N = 3), and ICE, IMVP-16, and EPOCH (N = 1 each). Complete response (CR) rate was 47.1%, and 14 patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 22 cases, and the most frequent site was the primary site (N = 20). Of note, relapse at central nervous system was found in 4 cases. Older age (≥ 55 years), advanced Lugano stage (IIE~IV), not achieving CR, and not receiving ASCT were associated with adverse OS. Conclusion: Although most patients had limited stage, the clinical outcomes of MEITL patients were dismal. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem to be essential. In addition, considering the frequent local failure, as well as the CNS relapse, novel therapeutic approaches are required to improve survival. Figure. Figure. Disclosures Kim: Mundipharma: Research Funding; Merck: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Roche: Honoraria, Research Funding; Kyowa-Kirin: Research Funding; Eisai: Honoraria, Research Funding; J&J: Research Funding; Celltrion: Honoraria, Research Funding; Novartis: Research Funding.

Description: B ackground The advent of new agents has contributed to the prolonged survival of multiple myeloma (MM) patients. From the Durie-Salmon staging system, international staging system (ISS) and recently, revised ISS (R-ISS) have been developed to better prognosticate the survival of MM. R-ISS includes chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization (iFISH) and lactate dehydrogenase (LDH) in addition to the ISS. However, the R-ISS has still some limitations in the real clinical settings, as it has enrolled patients exclusively on clinical trials which includes more young patients (age 〈 65 years old), contains non-standardized iFISH results and has short median follow-up duration. The first-line drugs used in the patients could also affect the prognosis. Therefore, a more detailed and standardized but also convenient prognostic system is needed with clinical findings commonly observed in MM patients treated with new agents in the real clinical world. Patient and Method Adult patients who were confirmed multiple myeloma between January, 2011 to December, 2017 and patients who had received thalidomide and/or bortezomib or lenalidomide-based chemotherapy as a first-line treatment were included for the analysis. A total of 861 patients from 13 centers participating Korean multiple myeloma working party were analyzed. Baseline serum albumin, serum ß2-microglobulin, cytogenetics by iFISH, LDH (lactate dehydrogenase), ALC (absolute lymphocyte count), CRP (C-reactive protein) and ferritin were measured within 4 weeks before beginning the first line of chemotherapy. Each factors of age ≥ 65 years, serum ß2-microglobulin ≥ 5.5 mg/L, LDH 〉 normal, cytogenetic high risk by FISH (del17p, t(4;14), t(14;16)), ALC 〈 1500/mm3, CRP ≥ 1.5 mg/dL, and ferritin ≥ 500 ng/mL were defined as abnormal findings, which were given 1 point (Table 1) and the sum of points were used to discriminate inflammatory factor-based staging system (IFBSS). IFBSS were defined as follows: Stage I (point 0), stage II (point 2-3), stage III (point 4-5), and stage IV (point 5-7). Overall survival (OS) was defined by the date of MM diagnosis to the date of death by any cause or follow-up loss. Results Baseline characteristics of the patients were as listed in Table 2. With a median follow-up duration of 22.70 months (range, 0.20-86.80 months), age ≥ 65 years, serum ß2-microglobulin ≥ 5.5 mg/L, LDH 〉 normal, cytogenetic high risk by FISH (del17p, t(4;14), t(14;16)), ALC 〈 1500/mm3, CRP ≥ 1.5 mg/dL, and ferritin ≥ 500 ng/mL showed significant higher OS by univariate and multivariate analysis. Albumin 〈 3.5 mg/dL were excluded into the staging system due the unpredictability to OS in univariate analysis (Table 3). Study groups of inflammatory factor-based scoring system comprised of 61 patients in stage I, 395 patients in stage II, 189 patients in stage III and 36 patients in stage IV. The median OS were not reached in stage I and II, stage III and IV showed a median OS of 36.57 months (95%CI, 33.96-.39.18) and 17.60 months (95%CI, 9.16-.26.04). The OS according to the IFBSS showed significant differences (P 〈 0.001), which predicted OS better compared with conventional ISS and R-ISS (Table 4). Conclusion In the new agent era, inflammatory factors incorporated into the staging system can better discriminate prognosis of multiple myeloma patients compared to the ISS or R-ISS. Validation of this finding in a larger cohort is needed to expand usage of this new staging system. Disclosures Yoon: Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Kyowa Hako Kirin: Research Funding; Janssen: Consultancy; Yuhan Pharma: Research Funding; Genentech, Inc.: Research Funding; MSD: Consultancy.

Description: Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening hematologic disorder leading to hemolytic anemia, which can occur concomitantly with bone marrow disorders (BMD), such as aplastic anemia (AA) and myelodysplastic syndrome (MDS). Accordingly, patients with PNH often require red blood cell (RBC) transfusions to treat anemia due to hemolysis or bone marrow failure. After demonstrating a non-inferior efficacy and safety profile in two of the largest clinical trials to date, ravulizumab was approved as a treatment for adults with PNH, including patients with an underlying history of bone marrow disease, who are transfusion dependent or independent. Aims: To assess the efficacy of ravulizumab in patients with PNH with or without an underlying pathology of AA or MDS, and to investigate the impact of ravulizumab on transfusion burden as measured by number of transfusions and total packed RBC (pRBC) units transfused over a 52-week period. Methods: This phase 3 multicenter, randomized, active-controlled, open-label study (study 301, NCT02946463) enrolled complement-inhibitor-naïve patients with PNH. Patients were aged ≥ 18 years with a confirmed diagnosis of PNH by flow cytometry and lactate dehydrogenase (LDH) level ≥ 1.5x the upper limit of normal (ULN; 246 U/L). Patients received either ravulizumab or eculizumab for 26 weeks; after which all patients received ravulizumab from week 26 to week 52. Efficacy outcomes included the proportion of patients achieving transfusion avoidance (TA), number of pRBC units transfused and the number of pRBC or whole blood transfusions (WBT) received from baseline to 26 and 52 weeks of treatment. In this retrospective analysis, outcomes were analysed for the following subgroups: AA, MDS or no BMD (medical history of AA or MDS was determined by the investigator at screening). Descriptive statistics were calculated for continuous (means) and categorical variables (numbers and percentages). Formal hypothesis testing for significance between treatment groups was not performed. Results: Of the 246 patients included in the study, 79 had a history of AA (32.1%) and 13 (5.3%) had a history of MDS. Baseline characteristics were comparable between treatment groups. From baseline to week 26, a comparable proportion of patients with AA achieved TA to those with no BMD; 75.6% for patients with AA and no BMD receiving ravulizumab, and 60.5% and 73.7% for patients with AA and no BMD receiving eculizumab, respectively (Table 1). Importantly, TA was maintained through 52 weeks, with similar proportions of patients with AA (87.1‒91.3%) maintaining TA to patients without BMD (85.7‒91.5%). More specifically, 65.9% of patients with AA and 69.2% of patients without BMD achieved TA through 52 weeks of ravulizumab treatment, and 55.3% and 63.2% of patients with AA and without BMD, respectively, achieved TA on eculizumab followed by ravulizumab. The proportion of patients with MDS who achieved TA appeared numerically lower compared with patients with AA or no BMD, however, this subgroup sample size was small. Furthermore, a lower proportion of patients on ravulizumab with AA or MDS received any transfusion from baseline to weeks 26 and 52 compared with those treated with eculizumab followed by ravulizumab: for week 26, 24.4% and 57.1% for ravulizumab versus 39.5% and 100.0% for eculizumab in patients with AA and MDS, respectively, and for week 52, 29.3% and 57.1% for patients with AA and MDS receiving ravulizumab for 52 weeks versus 44.7% and 100.0% for patients with AA and MDS treated with eculizumab followed by ravulizumab. In addition, ravulizumab-treated patients with AA or MDS had numerally fewer transfusions and units of pRBC/WBT compared with those who received eculizumab followed by ravulizumab. Overall, the exploratory nature of the analysis and small sample size means that interpretation of the data is limited. Conclusions: This analysis demonstrates that majority of patients with PNH and AA who received ravulizumab avoided the need for transfusion up to 52 weeks of treatment. Patients treated with ravulizumab for the 52-week period had numerically fewer transfusions and units of pRBC/WBT transfused compared with patients who received eculizumab followed by ravulizumab. Overall, these findings support the use of ravulizumab in complement-inhibitor-naïve patients with PNH, with or without a history of BMD. Disclosures Risitano: Amyndas: Consultancy; Samsung: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; RA pharma: Research Funding; Pfizer: Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biocryst: Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees. Schrezenmeier:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Yonemura:Alexion Pharmaceuticals: Honoraria, Research Funding. Munir:Alexion: Honoraria; F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Pavani:Alexion Pharmaceuticals: Current Employment. Wang:Alexion Pharmaceuticals Inc.: Current Employment. Kulagin:Alexion Pharmaceuticals Inc.: Consultancy, Research Funding. Kulasekararaj:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sicre de Fontbrune:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Röth:Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Biocryst: Consultancy, Honoraria; Apellis: Consultancy, Honoraria; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Research Funding.