bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS1228 SF3B1 KNOCKDOWN AT EARLY ERYTHROPOIESIS INDUCED CELL APOPTOSIS BY USING A TET‐ON LENTIVIRAL VECTOR
Authors: Huang Y. , Wu X. , Sun L. , An X. 
Published: June 2019

Background:SF3B1 has been drawing great interests of scientists due to their significantly high mutation frequency in one kind of hematological disease Myelodysplastic syndromes‐Refractory anemia with ring sideroblasts (MDS‐RARS), which is characterized by the anemia in clinic. However, the physiological roles of SF3B1 in erythropoiesis are poorly studied.Aims:To elucidate the biological functions of SF3B1 in specific stages of human erythropoiesis through precise temporal control of SF3B1 expression. To test the efficiency and safety of the new TET‐on lentiviral vector in differentiating cells.Methods:TET‐on lentiviral vector was constructed for conditional gene knockdown. Undifferentiated CD34+ cells were transduced with the Lentivirus and SF3B1 gene knockdown was induced by doxycycline in different differentiation stages across human erythropoiesis. The efficiency and safety of the TET‐on lentiviral vector were assessed by monitoring green fluorescent protein expression and erythroblasts differentiation, respectively. Knockdown of SF3B1 gene was checked by using qRT‐PCR and western blot analyses. The effects of SF3B1 ablation on progenitors were detected by colony forming assay and apoptosis was assessed by flow cytometry.Results:The TET‐on vector is efficient and safe for erythroblasts with no disturbance to the proliferation, differentiation, morphology and enucleation. Knockdown of SF3B1 in erythroblasts impairs erythroid colony forming and induced cell apoptosis. Interestingly, knockdown of SF3B1 shows temporal effects on erythropoiesis: in early stages, the deficiency of SF3B1 leads to significant cell apoptosis; however, it has no effect on cell growth at late stages of erythropoiesis.Summary/Conclusion:Our findings indicate that the TET‐on lentiviral vector is a powerful tool for precise temporal control of gene expression in differentiating cells, and SF3B1 is critical for the growth of early erythropoiesis.
PS1253 MAGNIFY: PHASE IIIB INTERIM ANALYSIS OF INDUCTION #R2 FOLLOWED BY MAINTENANCE IN PATIENTS WITH RELAPSED/REFRACTORY INDOLENT NON‐HODGKIN LYMPHOMA
Authors: Rummel M.J. , Andorsky D.J. , Coleman M. , Yacoub A. , Melear J.M. , Fanning S.R. , Kolibaba K.S. , Lansigan F. , Reynolds C. , Foon K. , Li J. , Llorente M. , Sharman J. 
Published: June 2019

Background:There is a lack of standard treatment approaches for patients with relapsed indolent non‐Hodgkin lymphoma (iNHL). Current study results with PI3K inhibitors have reported a median PFS of <1 y in the relapsed/refractory setting (R/R) for patients with iNHL. Lenalidomide, an immunomodulatory agent, enhances the activity of rituximab when combined into a regimen known as R2, which has recently reported a median PFS of 39.4 mo in patients with R/R iNHL patients from the phase III AUGMENT study (Leonard. ASH 2018:445).Aims:These analyses examine the interim primary endpoint of overall response rate (ORR; 1999 IWG) for induction R2 in efficacy‐evaluable patients receiving ≥ 1 treatment and who have available baseline and post‐baseline assessments.Methods:The multicenter, non‐registrational phase IIIb MAGNIFY trial in patients with R/R follicular lymphoma (FL) grade 1–3a and marginal zone lymphoma (MZL) was designed to determine the optimal duration of lenalidomide (NCT01996865). R2 treatment includes lenalidomide 20 mg/d, d1–21/28 plus rituximab 375 mg/m2/wk cycle 1 and q8wk cycles 3+ given for 12 cycles, and is followed by 1:1 randomization in patients with stable disease or better to continued R2 vs rituximab maintenance.Results:370 enrolled patients (80% FL grade 1–3a; 20% MZL) had a median age of 66 y, 83% stage III/IV disease, and a median of 2 prior therapies (95% prior rituximab‐containing). At a median 16.7 mo follow‐up, efficacy‐evaluable patients demonstrated a 73% ORR and 45% complete response (CR; Table). Similar efficacy results were shown for patients by histology. Overall, the median time to response (TTR) was 2.7 mo, median duration was response (DOR) was 36.8 mo, and median progression‐free survival (PFS) was 36.0 mo. According to their refractory status to rituximab at baseline, patients who were rituximab‐refractory and non‐refractory, respectively, had an ORR (CR) of 63% (40%) and 78% (47%), and median PFS of 18.1 mo and not reached. Of 370 patients who were randomized, 142 (38%) have entered the maintenance phase. The most common all‐grade adverse events were 48% fatigue, 40% neutropenia, 35% diarrhea, 30% nausea, and 29% constipation. Although the grade 3/4 adverse event neutropenia was 34%, all others were <6%.Summary/Conclusion:R2 therapy is an active treatment regimen in patients with R/R FL grade 1–3a and MZL, including patients refractory to rituximab, and with a tolerable safety profile.image
PS1258 CLONAL B‐CELL LYMPHOCYTOSIS OF MARGINAL ZONE ORIGIN (CBL‐MZ): CLINICAL SIGNIFICANCE OF ABSOLUTE CLONAL B CELL COUNTS
Authors: Kalpadakis C. , Pangalis G. , Konstantinou I. , Sachanas S. , Tsirkinidis P. , Moschogiannis M. , Yiakoumis X. , Siakantaris M. , Tsaftaridis P. , Iliakis T. , Befani M. , Dimopoulou M. , Asimakopoulos I. , Dimitrakopoulou A. , Butsikas G. , Korkolopoulou P. , Kontopidou F. , Koulieris E. , Pontikoglou C. , Ximeri M. , Psylaki M. , Roumelioti M. , Rontogiannis D. , Papadaki H. , Panagiotidis P. , Vassilakopoulos T. , Angelopoulou M. 
Published: June 2019

Background:CLL‐like MBL is divided into low and high count, with significant clinical and biological differences. No studies have been conducted so far in CBL‐MZ.Aims:In accordance to the proposed grouping of CLL‐like MBL, we aimed to investigate the clinical significance of such distinction in MZL‐like MBL.Methods:95 consecutive CBL‐MZ cases were analyzed, with any number of circulating CD5‐ CBL, no B‐symptoms, organomegaly, lymphadenopathy, cytopenias or any other features indicating a known lymphoproliferative disorder. Patients were grouped in 3 categories: A. low count (CBL≤500/μL), B. high count (CBL > 500/μL and ≤5000/μL) and C. frank lymphocytosis (CBL>5000/μL). Using this subdivision a comparison of several laboratory and disease evolution parameters was performed.Results:3/95 patients belonged to group A, 59 to group B and 33 to group C. The characteristics and outcome of the three groups are shown in table. Apart from WBC, ALC and CBL that differed significantly by definition, the only parameters that were statistically different between the three groups, were absolute neutrophil counts, CD11c expression, BM infiltration, and the frequency of evolution to SMZL. More specifically, the frequency of CD11c expression was highest in group C (68%) compared to group B (33%) and A (0%). Surprisingly, ANC were significantly higher with rising ALC. The percentage of BM infiltration differed significantly between the three groups and was highest in the lymphocytosis group (C); however, this difference was mainly due to the difference between group B and C. Notably, the three patients with low‐count MBL had BM infiltration between 30–40%, which was similar to the group C. There was a trend for a higher frequency for SMZL evolution in group C. Four out of 5 patients who evolved to SMZL belonged to the group C, whereas the remaining one patient had a low‐count MBL. At a median follow‐up time of 42 months, need of therapy, time to progression (TTP), time to treatment (TTT) and overall survival (OS) did not differ significantly between the three groups. Not CBL counts, but elevated LDH and BM infiltration≥50% were the only significant factors for TTT by multivariate analysis. Treatment due to cytopenias was more frequent in group B.Summary/Conclusion:CBL‐MZ patients have an excellent prognosis. The cut‐off of 5x109//L CBL does not seem to be the optimal threshold to distinguish prognostically different subgroups, with the exception of SMZL development. BM infiltration≥50% and elevated LDH are associated with shorter TTT.image
PS1260 EFFICACY OF MOGAMULIZUMAB IN PREVIOUSLY TREATED PATIENTS WITH LESS ADVANCED MYCOSIS FUNGOIDES: RESULTS FROM THE MAVORIC STUDY
Authors: Zinzani P.L. , Scarisbrick J. , Bagot M. , Fisher D.C. , Elmets C. , Duvic M. , Beylot‐Barry M. , Kim E.J. , Moriya J. , Leoni M. , Geskin L.J. 
Published: June 2019

Background:In the MAVORIC Phase 3 study, patients (pts) with previously treated mycosis fungoides (MF)/Sézary syndrome (SS) stage IB‐IVB who received mogamulizumab (MOGA) had significantly prolonged progression‐free survival and greater overall response rates (ORRs) compared to pts on vorinostat (VORI) (Kim et al. Lancet Oncol 2018). Less advanced MF (stage IB/IIA) is a chronic skin malignancy that can involve blood and lymph nodes and may require many lines of systemic therapy over the disease course.Aims:This post‐hoc analysis specifically examined efficacy and safety of the recently approved MOGA in stage IB/IIA MF pts.Methods:In MAVORIC, stage IB‐IVB MF/SS pts who were treated with ≥1 prior systemic therapy were randomized to MOGA or oral VORI. In the post‐hoc analysis, time to next treatment (TTNT) was defined as time to any therapy excluding topical steroids or focal radiation treatment. ORR was based on global composite response in 4 disease compartments – skin, blood, lymph nodes, and viscera – achieved at 2 consecutive visits at least 8 weeks apart. Individual compartment responses were also assessed.Results:A total of 85 pts with stage IB/IIA CTCL were included (MOGA, IB n = 15, IIA n = 21; VORI, IB n = 27, IIA n = 22). Overall, 24% (10/42) of IB pts and 28% (12/43) of IIA pts had received ≥6 prior therapies. Median TTNT with MOGA in IB pts was 11.5 months (mo) (95% CI, 1.4,16.0) compared to 3.1 mo (95% CI, 2.7, 5.3) with VORI; in IIA pts, median TTNT was 10.1 mo (95% CI, 5.5, 12.6) and 4.9 mo (95% CI, 2.4, 8.0), respectively. ORR in IB pts receiving MOGA and VORI was 20% (3/15) and 18.5% (5/27), respectively; ORR in IIA was 19% (4/21) and 0% (0/22), respectively. For stage IB and IIA, compartmental response rates with MOGA were – skin: 20% (3/15) and 38% (8/21), blood: 0% (0/2) and 75% (6/8), and lymph nodes: 0% (0/0) and 15% (3/20), respectively. Adverse events were generally manageable and consistent with the ITT population.Summary/Conclusion:Though MAVORIC was not powered to determine treatment effect by disease stage, this post‐hoc analysis of TTNT, ORR, and compartmental response in stage IB/IIA demonstrates meaningful clinical benefit with MOGA in previously treated, less advanced MF pts.
PS1275 INVASIVE ASPERGILLOSIS CAUSED BY ”RARE“ PATHOGENS: CLINICAL REGISTRY DATA ANALYSIS
Authors: Shadrivova O. , Ryabinin I. , Desyatik E. , Borzova Y. , Volkova A. , Popova M. , Bogomolova T. , Zubarovskaya L. , Afanasyev B. , Vasilyeva N. , Klimko N. 
Published: June 2019

Background:Publications describing invasive aspergillosis (IA) caused by “rare” pathogens are limited. Species identification of the pathogen is necessary for the selection of antifungal therapy, as some Aspergillus spp. may be resistant to antifungal drugs.Aims:Analysis clinical registry data of patients with IA caused by “rare” pathogensMethods:Retrospective analysis of patients with IA caused by “rare” pathogens in 1998–2019 yy. For the IA diagnosis EORTC / MSD, 2008 criteria were used. In accordance with the European guidelines, DNA sequencing and MALDI‐TOF were used to identify of the “rare” Aspergillus spp.Results:In our registry we included 800 patients with IA. In 227 patients Aspergillus spp. were isolated. The “rare” pathogens were detected in 18 (8%), and these patients were included in group I; age varied from 5 to 67 years, median – 40.5,males – 50%. The control group consisted 209 patients with other Aspergillus spp. (A. fumigatus,A. niger and A. flavus), from 1 to 99 years old, median ‐ 47, males – 53%. In both groups IA predominantly occurs in patients with hematologic malignancies (73% vs 76%): acute leukemia – 27% vs 33%, lymphoma – 22% vs 27%, multiple myeloma 12% vs 6%, chronic leukemia 6% in each group, other hematological diseases – 6% vs 4%. We identified, IA caused by ”rare“ pathogens more often developed in children(22% vs 11%, p < 0.05).In addition to standard risk factors, in patients with ”rare“ pathogens more often was detected lymphocytopenia 67% vs 55%, with duration 21 vs 14 days, p < 0.05, less frequent was noted fever (46% vs 78%, p <  0.05), but significantly more lung damage accompanied by hemoptysis (17% vs 10%, p <  0.05). “Rare” pathogens were A. ustus – 38%, A. nidulans – 22%, A. calidoustus – 8%,A. versicolor– 8%,A.glaucus – 8%,A. candidus – 8%, andA. sydowii – 8%. In controlgroup etiological agents were A. fumigatus – 52%,A. niger – 31%, A. flavus– 17%. Two or more species of Aspergillus were isolated in 44% vs 9%, p < 0.05. Antifungal therapy was used in 100% vs 97% of patients. Twelve weeks overall survival rate was 82% vs 81%. In the group with “rare” pathogens more frequently observed relapse of IA – 33% vs 12%, p <0.05.Summary/Conclusion:Patients with “rare” pathogens account for 8% of patients with isolated Aspergillus spp. cultures. IA caused by ”rare“ pathogens, more often occurs in children – 22%. The features of IA caused by “rare” pathogens are: long‐term lymphocytopenia (67%, median ‐ 21 days), combination of two or more pathogens – 44%, high relapse rate – 33%. Survival of patients with “rare” pathogens does not differ from the total cohort of patients – 82%.
PS1286 INVASIVE YEAST INFECTIONS IN HEMATOLOGICAL PATIENTS AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Popova M. , Rogacheva Y. , Volkova A. , Markova I. , Frolova A. , Shvetcov A. , Nikolaev I. , Goloshchapov O. , Bykova T. , Paina O. , Gevorgian A. , Darskaya E. , Vladovskaya M. , Bondarenko S. , Moiseev I. , Baykov V. , Zubarovskaya L. , Klimko N. , Afanasyev B. 
Published: June 2019

Background:Invasive yeast infection is rare invasive fungal disease but associated with high mortality rate in hematological patients. Data on Invasive yeast infection in hematopoietic stem cell transplantation (HSCT) recipients are limited.Aims:The aim of our study was to estimate epidemiology of invasive yeast infections in large HSCT recipients’ cohort for the 10‐year period transplant activity in CIC725.Methods:Between 2008 and 2017 2430 stem cell transplantation have been performed in CIC 725: 1647 allogeneic HSCT and 783 autologous HSCT. A retrospective study included 30 cases of invasive yeast infections in patients with hematological malignances and non‐malignant hematological diseases after HSCT. EORTC/MSG 2008 criteria were used for the diagnosis of proven yeast infections as well as to evaluate response to therapy.Results:Incidence of invasive yeast infections for the 10‐year period of high transplant activity was 1,2%: 1,4% in allo‐HSCT recipients (n = 23), 0,9% – auto‐HSCT (n = 7) predominantly in patients with acute leukemia – 67% (n = 20). The median age was 10 y.o. (range, 1 month‐59 years). In study population allo‐HSCT from unrelated donor was performed in 50% (n = 15), haplo‐HSCT in 27% (n = 8) and auto‐HSCT in 23% (n = 7). In study cohort 30% of patients had no complete remission at the moment of HSCT. As a primary antifungal prophylaxis was used: fluconazole – 37% (n = 11), echinocandins – 13% (n = 4), without prophylaxis – 23% (n = 7); as a secondary prophylaxis – voriconazole in 27% (n = 8). The median day of onset of invasive yeast infections after allo‐HSCT was 109 days (3–1337), auto‐HSCT – 20 days (8–33). The etiology of invasive yeast infections was: Candida spp. – 87% (n = 26), Malassezia furfur – 7% (n = 2), Trichosporon asahii – 3% (n = 1), Cryptococcus spp. – 3% (n = 1). Febrile fever was the main clinical symptom and septic syndrome developed in 60% of cases. OS at 30 days from diagnosis of invasive yeast infection was 63%. The central venous catheter removal was the only factor significantly improved OS at 30 days after invasive yeast infection diagnosis (91% vs 17%, p = 0,001).Summary/Conclusion:Incidence of invasive yeast infections for the 10 years of observation was 1,2%: 1,4% in allo‐HSCT recipients, 0,9% – auto‐HSCT. The main etiology was Candida spp. (87%). Overall survival at 30 days from the diagnosis of invasive yeast infections was 60%. Removing of central venous catheter improved overall survival in hematological patients after HSCT with invasive yeast infections.
PS1290 HEPARIN‐ANALOGUE SEVUPARIN INHIBITS STREPTOCOCCUS‐INDUCED VASCULAR HYPERPERMEABILITY THROUGH NEUTRALIZING NEUTROPHIL‐DERIVED PROTEINS
Authors: Wahlgren M. , Rasmuson J. , Kenne E. , Soehnlein O. , Lindbom L. 
Published: June 2019

Background:Acute lung injury (ALI) and respiratory distress can develop as a consequence of sepsis with pathogens such as Group A streptococcus (GAS) including S. pyogenes. In the pathogenesis of sepsis‐associated ALI, plasma exudation and leukocyte accumulation in the lungs are central events, and endothelial barrier disruption brought on by degranulation of neutrophil‐derived proteins is considered a causative factor. Heparin and heparin derivatives have been suggested as novel therapeutics in sepsis on the basis of their pleiotropic anti‐inflammatory effects.Aims:Here, we study wheter sevuparin, a heparinoid wihich lacks anticoagulant activity, affects neutrophil‐induced lung plasma leakage.Methods:A murine model of systemic inflammation evoked by heat‐killed GAS and furthermore, we utilized human neutrophils and endothelial cell monolayersResults:We demonstrate that sevuparin inhibits hkGAS‐induced endothelial barrier disruption by neutralizing the activity of neutrophil‐derived proteins. By mass spectrometry of neutrophil secretion we identify candidate proteins, including serprocidins, S100 proteins and histone H4, that interact with sevuparin and that are responsible for the disruptive effect on endothelial integrity.Summary/Conclusion:Collectively, our results corroborate the role of neutrophil‐derived proteins in vascular hyperpermeability caused by Group A streptococci, and suggest sevuparin as a potential therapeutic in acute neutrophilic inflammation.
PS1300 A NURSE LED IRON INFUSION CLINIC REDUCES POTENTIAL PATIENT HARM AND IMPROVES HOSPITAL EFFICIENCY
Authors: Newman L. , Wright T. 
Published: June 2019

Background:The introduction of a rapid iron infusion protocol (ferric carboxymaltose) whilst more convenient and safe for patients has the potential to change the management of iron deficiency anaemia (IDA) away from best practice guidelines. Latrobe Regional Hospital (LRH) deliver all outpatient intravenous (IV) iron infusions through their chemotherapy day unit (CDU), providing an opportunity to study the total prescribing practices in a busy rural referral centre.Aims:To assess the appropriateness of intravenous iron prescribing in a regional setting and implement service improvement projects where deviations from best practice were identified.Methods:Baseline data of all IV iron infusions was collected from May 2017 to January 2018 (PRE phase 9 months). From February to October 2018 (POST‐phase 9 months), referrals from primary care physicians requesting an iron infusion were assessed by a haematology clinical nurse consultant (CNC) iron infusion clinic with physician supervision. All internal medicine specialist requests for iron infusions were coordinated by the haematology CNC. Iron infusion and prescribing rates were summarised for three groups, physician, local medical officer (LMO) and obstetrics and gynaecology (O & G). All requests for iron infusions were assessed according to best practice guidelines.Results:Table one summarises the total 311 iron infusions delivered over the 9‐month pre‐phase data collection period. The physician group referred an older population of both males and females. The LMO referral group were predominantly female.Figure one shows the average monthly IV iron infusions delivered for the entire collection period and as per each referral group.There was a significant reduction in the average monthly IV iron infusions from 38 to 23. Monthly infusions delivered following referrals from the LMO group reduced significantly from 17 to 6. Whilst referrals from the physician group increased and O & G group decreased, these were not significant.Summary/Conclusion:The development of an iron infusion clinic led by a haematology CNC provides a safe evidenced based assessment of patient referrals. This model significantly reduced the rate of iron infusions in our regional hospital, allowing more efficient use of the expert outpatient infusion centre services and reducing potential harm related to an inappropriate therapy.image
PS1358 POTENT ANTI‐MYELOMA EFFICACY OF DENDRITIC CELL THERAPY IN COMBINATION WITH POMALIDOMIDE AND PROGRAMMED DEATH‐LIGAND 1 BLOCKADE IN A PRECLINICAL MODEL OF MULTIPLE MYELOMA
Authors: Jung S.‐H. , Chu T.‐H. , Vo M.‐C. , Park H.‐S. , Lakshmi T.J. , Ahn S.‐Y. , Kim H.‐J. , Lee J.‐J. 
Published: June 2019

Background:Dendritic cell (DC)‐based vaccines are recognized as a promising immunotherapeutic strategy against cancer, and various combination approaches have been developed to enhance DC function by modulating immune responses and tumor microenvironment.Aims:In this study, we investigated the efficacy of DC vaccination in combination with pomalidomide and programmed death ligand‐1 (PD‐L1) blockade in a murine model of multiple myeloma (MM).Methods:MOPC‐315 cell lines were injected subcutaneously to establish MM bearing mice. Four test groups were used to mimic clinical protocol: (1) PBS control, (2) DCs + pomalidomide/dexamethasone, (3) Pomalidomide/dexamethasone + PD‐L1 blockade, and (4) DCs + pomalidomide/dexamethasone + PD‐L1 blockade.Results:The combination of DCs + pomalidomide with dexamethasone + PD‐L1 blockade inhibited more strongly tumor growth and prolonged survival of treated mice compared to the other groups. This effect was associated with a significant reduction in immune suppressor cells, such as myeloid‐derived suppressor cells, regulatory T cells, and M2 macrophages, and level of immunosuppressive factors, such as vascular endothelial growth factor, transforming growth factor‐β, and interleukin‐10, and with the significant induction of immune effector cells, such as CD4+ and CD8+ T cells, memory T cells, natural killer (NK) cells, and M1 macrophages, in the spleen and tumor microenvironment. Functional activities of cytotoxic T lymphocytes and NK cells in spleen were also enhanced by the combination of DCs + pomalidomide with dexamethasone + PD‐L1 blockade.Summary/Conclusion:The collective findings in the murine MM model suggest that DC vaccination combined with pomalidomide and PD‐L1 blockade synergistically enhance antitumor immunity through two‐way mechanism, which inhibits immunosuppressive cells while activating effector cells with superior polarization of the Th1/Th2 balance in favor of the tumor immune response.