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  • American Society of Hematology  (35.540)
  • Düsseldorf : Sozialdemokratische Gemeinschaft für Kommunalpolitik in NRW
  • 2020-2023  (1)
  • 2010-2014  (35.542)
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  • 1
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    Düsseldorf : Sozialdemokratische Gemeinschaft für Kommunalpolitik in NRW
    Publikationsdatum: 2022-02-18
    Beschreibung: Dieser Beitrag zeigt, dass es sich bei der Strompreisentwicklung um eine ungerechte Verteilung von Lasten und Vorteilen zwischen verschiedenen Kundengruppen handelt und dass von einer Gefährdung des Industriestandortes nicht die Rede sein kann, sondern ganz im Gegenteil, die Industrie zu den wesentlichen Nutznießern der Energiewende zählt. Denn während stromintensive Industriekunden von nahezu allen Lasten befreit werden, profitieren sie zudem von immensen finanziellen Kostenvorteilen beim Strombezug, der durch den Ausbau regenerativer Energien entsteht (Merit-Order-Effekt). Vor allem die Haushaltskunden zahlen momentan für die größte industriepolitische Herausforderung seit dem zweiten Weltkrieg, nämlich den nahezu kompletten Umbau unserer Stromversorgung.
    Schlagwort(e): ddc:300
    Repository-Name: Wuppertal Institut für Klima, Umwelt, Energie
    Sprache: Deutsch
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  • 2
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    Düsseldorf : Sozialdemokratische Gemeinschaft für Kommunalpolitik in NRW
    Publikationsdatum: 2022-02-18
    Beschreibung: In seinem Beitrag "Ich will, wenn du willst" thematisiert Michael Kopatz individuelle, institutionelle und wirtschaftliche Beweggründe, die Bürger(innen) und Kommunen davon abhalten, sich für den Klimaschutz einzusetzen.
    Schlagwort(e): ddc:300
    Repository-Name: Wuppertal Institut für Klima, Umwelt, Energie
    Sprache: Deutsch
    Materialart: bookpart , doc-type:bookPart
    Format: application/pdf
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  • 3
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    Düsseldorf : Sozialdemokratische Gemeinschaft für Kommunalpolitik in NRW
    Publikationsdatum: 2022-02-18
    Beschreibung: Ein attraktives Nahverkehrsangebot ist sozial- und umweltpolitisch unverzichtbar. Fehlende Finanzierungsmöglichkeiten der Kommunen gefährden den erforderlichen Ausbau des ÖPNVs. Eine Diskussion über Finanzierungsalternativen ist daher notwendig. Eine Möglichkeit dazu wäre, den Nahverkehr in Zukunft nach dem Vorbild des Rundfunkbeitrages für Haushalte durch eine allgemeine Umlage zu finanzieren - dem Bürgerticket.
    Schlagwort(e): ddc:380
    Repository-Name: Wuppertal Institut für Klima, Umwelt, Energie
    Sprache: Deutsch
    Materialart: bookpart , doc-type:bookPart
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  • 4
    Publikationsdatum: 2022-08-22
    Beschreibung: © The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Aymonnier, K., Ng, J., Fredenburgh, L. E., Zambrano-Vera, K., Muenzer, P., Gutch, S., Fukui, S., Desjardins, M., Subramaniam, M., Baron, R. M., Raby, B. A., Perrella, M. A., Lederer, J. A., & Wagner, D. D. Inflammasome activation in neutrophils of patients with severe COVID-19. Blood Advances, 6(7), (2022): 2001–2013, https://doi.org/10.1182/bloodadvances.2021005949.
    Beschreibung: Infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the inflammasome in monocytes and macrophages and leads to the cytokine storm in COVID-19. Neutrophils, the most abundant leukocytes, release neutrophil extracellular traps (NETs), which have been implicated in the pathogenesis of COVID-19. Our recent study shows that activation of the NLRP3 inflammasome is important for NET release in sterile inflammation. However, the role of neutrophil inflammasome formation in human disease is unknown. We hypothesized that SARS-CoV-2 infection may induce inflammasome activation in neutrophils. We also aimed to assess the localization of inflammasome formation (ie, apoptosis-associated speck-like protein containing a CARD [ASC] speck assembly) and timing relative to NETosis in stimulated neutrophils by real-time video microscopy. Neutrophils isolated from severe COVID-19 patients demonstrated that ∼2% of neutrophils in both the peripheral blood and tracheal aspirates presented ASC speck. ASC speck was observed in neutrophils with an intact poly-lobulated nucleus, suggesting early formation during neutrophil activation. Additionally, 40% of nuclei were positive for citrullinated histone H3, and there was a significant correlation between speck formation and nuclear histone citrullination. Time-lapse microscopy in lipopolysaccharide -stimulated neutrophils from fluorescent ASC reporter mice showed that ASC speck formed transiently and at the microtubule organizing center long before NET release. Our study shows that ASC speck is present in neutrophils from COVID-19 patients with respiratory failure and that it forms early in NETosis. Our findings suggest that inhibition of neutrophil inflammasomes may be beneficial in COVID-19.
    Beschreibung: P.M. received an Individual Marie Skłodowska-Curie Actions fellowship by the European Commission (796365 - COAGULANT). This work was supported by the National Institutes of Health (NIH)/Research Program Award grant R35 HL135765 (D.W.), by the NIH/National Heart, Lung, and Blood Institute grant T32 HL007633-35 (J.N.), and by the NIH/National Institute of Allergy and Infectious Diseases grant U01AI138318 (J.L and M.P); by the Massachusetts Consortium on Pathogen Readiness (MassCPR) Evergrande COVID‐19 Response Fund Award to B.R.; and by a generous gift to D.W. from the Steven Berzin family.
    Schlagwort(e): Phagocytes ; Granulocytes ; Myelopoiesis
    Repository-Name: Woods Hole Open Access Server
    Materialart: Article
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  • 5
    Publikationsdatum: 2014-12-06
    Beschreibung: Hyperhaemolysis is a rare, poorly understood complication of red cell transfusion. We report the outcomes of SCT in 2 boys of Middle Eastern origin who developed life-threatening hyperhaemolysis each following their third transfusion for β-TM at the ages of 2.5 and 4 years. The diagnosis of hyperhaemolysis was based on laboratory evidence for haemolysis, post-transfusion haemoglobin (Hb) levels lower than pre-transfusion, positive Coomb’s tests and no allo-antibody able to be identified. Haemolysis was intravascular, extravascular and severe. Precipitous drops in Hb made transfusion unavoidable. The first boy responded to prednisolone, intravenous immunoglobulin (IVIG) and splenectomy. Haemosidderosis and fibrosis were present on liver biopsy, he was therefore regarded as a Class 3 thalassaemia patient and received hydroxyurea, azathioprine, erythropoietin, desferrioxamine, busulfan, cyclophosphamide and fludarabine conditioning prior to an HLA identical sibling SCT. He is alive and well 7 years post BMT with 30% stable donor chimerism and a normal Hb. The second child’s hyperhaemolysis failed to respond to prednisolone, IVIG, rituximab and splenectomy. Provision of the large number of suitably matched red cell units required was problematic. After receiving hydroxyurea, azathioprine, desferrioxamine, busulfan, cyclophosphamide, fludarabine, thiotepa and antithymocyte globulin (ATG) preparation for a CD3/CD19 depleted maternal haplotype peripheral blood SCT, the haemolysis finally stopped. Post-transplant severe veno-occlusive disease and multi-organ failure (MOF) required dialysis and ventilation. The maternal graft was rejected so 28 days after the first transplant he received a 4/6 mismatched unrelated cord blood transplant (UCBT) following further fludarabine and ATG, which fully engrafted. He recovered from MOF and was discharged from hospital 47 days after the UCBT, transfusion independent. On day +86 he contracted Respiratory Syncytial Virus chest infection with acute intravascular haemolysis necessitating transfusions. Fulminant liver failure developed, presumably due to iron toxicity, and death occurred on day +102, having received 112 transfusions in the 12 months since presentation. In conclusion, avoiding red cell transfusion is not always possible in hyperhaemolysis, especially in β-TM. Patients may quickly become classified as Class 3 in terms of predicting BMT outcome. Immune modulation therapy and SCT was effective in 1 case but only temporarily stopped haemolysis in the other, despite full engraftment ultimately being achieved with a mismatched UCBT. SCT should be considered early in cases of hyperhaemolysis in β-TM because it can potentially cure both and result in transfusion independence. Disclosures Off Label Use: Intravenous immunoglobulin and rituximab for treatment of haemolytic anaemia; hydroxyurea, azathioprine, fludarabine, erythropoeitin, busulphan, cyclophosphamide, thiotepa and antithymocyte globulin for use in stem cell transplantation in children with thalassaemia.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
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  • 6
    Publikationsdatum: 2014-12-06
    Beschreibung: Background: Post-remission treatment for AML is very aggressive and many times a SCT is needed. Comparisons between Allo-SCT and Auto-SCT ve always shown more Transplant Related Mortality (TRM) but less Cumulative Incidence of Relapse (CIR) in the first group. Our study describes, not only the long-term survival outcomes, but also the quality of life in long survivors. Methods: Retrospective study of 274 patients diagnosed with non-promyelocytic AML who underwent SCT between 1982 and 2011 in our center. Characteristics in the 162 Allo-SCT and the 112 Auto-SCT groups of patients were respectively: median age of 38 and 45 years old, secondary AML in 20% and 10%, refractory to Induction AML in 16% and 3%, pre-SCT status different from Complete Remission (CR) in 13% and 3% and year of SCT before 2005 in 53% and 86%. No significant differences between both groups were found in other risk factors as hyperleucocytosis at diagnosis or adverse cytogenetics. Results: With a median follow-up of 55 months [2-316], Overall Survival (OS) until 1997 in Allo-SCT and Auto-SCT were respectively, 40% and 61% at 1 year and 28% and 45% at 5 years (figure 1), but from 1997, 66% and 70% at 1 year and 47% and 48% at 5 years (figure 2). Disease Free Survival (DFS) until 1997 in Allo-SCT and Auto-SCT were respectively, 50% and 65% at 1 year and 38% and 46% at 5 years, but from 1997, 67% and 63% at 1 year and 52% and 47% at 5 years. In the last 15 years, no differences were found between both groups in OS nor DFS. CIR in Allo-SCT and Auto-SCT were respectively, 18% and 32% at 1 year and 24% and 50% at 5 years, without dependence on year of SCT. No relapse was observed later in any group. TRM until 1997 in Allo-SCT and Auto-SCT were respectively, 30% and 7% at 1 year and 35% and 9% at 5 years, but from 1997, 16% and 2% at 1 year and 25% and 4% at 5 years. Multivariable analysis showed that the only risk factor with a negative impact on OS was not having achieved CR at the time of SCT. Other variables as older age, hyperleucocytosis at diagnosis, adverse cytogenetics, secondary AML or sooner year of SCT lost their univariable analysis significance. Allo-SCT: From the 162 patients, 72(44%) are alive by this moment, 43(60%) with ECOG 0, 21(29%) with ECOG 1 and the other 8(11%) with ECOG 2, basically because of graft versus host disease (GVHD in 39 patients, 21 steroid-dependent and 3 refractory to any treatment). All of them have been in CR during the last 2 years of follow-up. In contrast, 90(56%) patients have died: 52(58%) because of SCT complications (20 infections, 16 GVHD, 8 toxicity and 8 mixed causes), 33(37%) because of disease and 5(5%) because of other causes. With a median follow-up of 43 months [2-316], there have been 4 secondary neoplasm, all of them solid ones, which appeared with a median of 242 months [179-311] from SCT. None of them had previously received radiotherapy. Auto-SCT: From the 112 patients, 43(38%) are alive by this moment, 32(74%) with ECOG 0 and the other 11(26%) with ECOG 1. All of them have been in CR during the last 2 years of follow-up. In contrast, 69(62%) patients have died: 45(65%) because of disease, 14(20%) because of SCT complications and 10(15%) because of other causes. With a median follow-up of 93 months [5-230], there have been 6 secondary neoplasm, 5 of them hematologic ones, which appeared with a median of 90 months [76-115] from SCT. None of them had received radiotherapy, but previously treated hematopoietic stem cells. Only one is alive at the time of last follow-up. Conclusions: In one hand, despite the high incidence of relapse in Auto-SCT in any period, OS is lower in Allo-SCT during the first years [1982-1996], although it has a tendency towards OS in Auto-SCT from 1997 because of the decrease in TRM, which is more significative in Allo-SCT. In the other hand, DFS is slightly higher in Allo-SCT during the last years [1997-2011], although the quality of life in long survivors is worse, basically because of GVHD. In summary, we have not really found differences between Allo-SCT and Auto-SCT in terms of OS and DFS in our series, so both procedures are efficient to treat AML (near 50% of the patients in both groups are alive at 5 years from SCT in recent years). The decrease in TRM until 4% at 5 years in Auto-SCT makes it a good choice, particularly for older patients without risk factors. However, the development of secondary hematologic neoplasms is a relevant fact, with an incidence of 11% and a high late mortality. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
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  • 7
    Publikationsdatum: 2014-12-06
    Beschreibung: By reducing treatment intensity allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become feasible for elderly patients. Different reduced-intensity conditioning (RIC) regimens are available, but there is little consensus about the optimal preparative regimen to use, in particular with regard to the outcomes counterbalancing the aim of feasibility and tolerability with higher rates of relapse. Here, we retrospectively evaluate the outcome of sequential therapy employing RIC with fludarabine 30 mg/m2, cytarabine 2g/m2 and amsacrine 100 mg/m2 for 4 days (FLAMSA; Schmid C et al. JCO 2005) followed by busulfan 10 x 0.8 mg/kg (FLAMSA-Bu) compared to RIC utilizing fludarabine 5 x 30 mg/m2, carmustine (BCNU) 2 x 150 mg/m2 and melphalan 110 mg/m2 (FBM; Marks R et al. Blood 2008) in elderly patients treated consecutively at our institution between July 2005 and October 2012. We analyzed the course of 114 patients (pts) with acute myeloid leukemia (AML; n=99) or myelodysplasia (MDS; n=15) aged ≥ 59 years with 59 pts aged ≥ 66 years who were treated with either FLAMSA-Bu (n=66; n=24 ≥ 66 years) or FBM (n=48; n=35 ≥ 66 years). All patients received sero-therapy with anti-thymocyteglobuline (ATG). Median patient age was 66 years for the entire cohort (68 years FBM; 64 years FLAMSA-Bu). 36 patients (75%) of the FBM and 42 patients (63 %) of the FLAMSA-Bu group suffered from high risk disease defined as relapsed or refractory AML or refractory anemia with excess of blasts in transformation (RAEB-T). The hematopoietic cell transplantation comorbidity index (HCT-CI) was higher for the patients of the FBM group than for the FLAMSA-Bu group with 26 (54 %) versus (vs) 24 patients (36 %) scoring ≥ 2 (p 0.085). Graft source after conditioning with FBM/FLAMSA-Bu was bone marrow (1/2), G-CSF mobilized peripheral blood stem cells (40/62) and double-umbilical cord-blood (7/1). In 23 pts (20 %) HLA-matched related and in 91 pts (80 %) HLA-matched unrelated donor transplantation was performed. Engraftment failure was observed in 1 patient after FLAMSA-Bu, while engraftment was achieved in all evaluable patients of the FBM group in a median of 23 days vs 18 days after FLAMSA-Bu (p 0.003), while 7 pts with double-umbilical cord-blood transplantation where included in the FBM group vs 1 pt in the FLAMSA-Bu group. Non-hematological treatment-related acute toxicity ≥ CTC III (gastrointestinal, hepatic, cardiovascular, renal, centralnervous system) occurred in 12/48 pts (25 %) after FBM and in 18/66 pts (27 %) after FLAMSA-Bu. Incidence of severe acute (III-IV) and chronic GvHD was 22.9 %/16.6 % for FBM vs 18.2 %/19.7 % for FLAMSA-Bu, respectively. After conditioning with FBM 2/48 pts vs 9/66 pts after FLAMSA-Bu were diagnosed with a secondary malignancy (p 0.08). Non-relapse mortality (NRM) after 12 months was 26.8 % for FBM versus 25.2 % for the FLAMSA-Bu group. Incidence of relapse after FBM vs FLAMSA-Bu conditioning was 22.9 % vs 15.2 % after 1 year and 31.3 % vs 16.7 % after 2 years. Occurrence of relapse was significantly related to an incomplete or mixed chimerism (donor cells ≤ 95 % in peripheral blood and/or bone marrow) at day +30 (p 0.001). After a median follow up of 31.4 months (range 4.4-97.5) estimated overall survival (OS) and relapse-free survival (RFS) after 2 years was 55.4 % and 51.4 % for the FBM vs 58 % and 56.7 % for the FLAMSA-Bu group, respectively. Analyzing different subgroups, FBM conditioning might be favorable for pts aged ≥ 66 years when suffering from high risk AML (n=26): Within this group 1-year OS after FBM vs FLAMSA-Bu was 71.4 % vs 66.7 % (p 0.58) and 1-year RFS was 71.4 % vs 58.3 % (p 0.59), respectively. Notably, for pts at highest risk (aged ≥ 66 years and suffering from secondary or therapy-related AML; n=24) the benefit of FBM conditioning becomes more pronounced: 1-year OS after FBM vs FLAMSA-Bu was 62.5 % vs 37.5 % (p 0.26) and 1-year RFS 54.2 % vs 37.5 % (p 0.17). Both conditioning regimens are feasible, and provide similar rates of acute toxicity, NRM and GvHD. There might be evidence for a benefit of conditioning with FBM for the subgroup of “the oldest patients at highest risk”. Taking into account that there is an increasing group of ‘medically fit’ elderly patients in the field of allogeneic transplantation, prospective clinical trials are needed to investigate different conditioning regimens considering their special requirements. Disclosures No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
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  • 8
    Publikationsdatum: 2014-12-06
    Beschreibung: Introduction Cerebral sinus venous thrombosis (CSVT) is potentially life-threatening thrombosis with mortality around 10%. Venous thromboembolism (VTE) is a common complication in children with cancer. These children have several thrombotic risk factors such as the malignancy itself, severe infections, prothrombotic medication and immobilization. The treatment of acute lymphoblastic leukemia (ALL) includes steroids and asparaginase (ASP), raising the VTE risk. In children with ALL the central nervous system (CNS) is a common localization for VTE. However, retrospective studies on small numbers of patients, larger studies and population-based data in children are scarce. The five Nordic countries, Estonia and Lithuania have a common treatment protocol for children with ALL between 1 and 18 years of age with prospective registration of toxicities, including CSVT offering a unique opportunity to study CSVT in this patient group. This is to our knowledge the largest report of children with ALL and CSVT describing the incidence, symptoms, treatment and the effect of CSVT on ALL treatment. Methods We assessed the symptoms, treatment, clinical risk factors and outcome of all children between ages 1 and 17 years at diagnosis of B-cell precursor or T-cell ALL between June 2008 and July 2013 and with CSVT. Data were collected from the patients’ medical records and the NOPHO leukemia registry. Results In total, 20 (1.9%) of the 1038 children with ALL treated according to the NOPHO ALL 2008 protocol developed CSVT. The cumulative incidence of CSVT was 2.0%. All the thromboses occurred within the first 5 months of treatment. The most common symptoms at the diagnosis of CSVT were headache, convulsions, weakness/fatigue and cerebral nerve palsy/hemiparesis/hemiplegia. The most frequent localizations for CSVT were sinus sagittalis (n=16) and sinus transversus (n=10). However, in most cases multiple cerebral veins were involved ( 70%). Median D-dimer at time of the CSVT diagnosis was 0.85 mg/L (range 0.19-4.7 mg/L) with 5 patients having normal D-dimer. We could not identify any clinical risk factors for CSVTs. CSVT was associated with steroids (treatment within 2 weeks before the diagnosis of CSVT) in 16/20 and with Pegylated asparaginase in 16/20. Fifteen patients were later screened for the inherited thrombophilic factors; one child had heterozygous prothrombin G20110A mutation and another heterozygous factor V (R506Q) Leiden mutation. Most patients (19/20) were treated with anticoagulants: mostly low molecular weight heparin (LMWH). The median treatment with LMWH was 26 weeks (range 14-119 weeks). No bleeding complications were observed in connection with LMWH. Two deaths were directly related to CSVT. Asparaginase was omitted from the treatment in 7 and delayed or reduced in 5 of the cases raising the risk for subsequent suboptimal leukaemia treatment. Of the surviving 18 patients, follow-up imaging revealed complete recanalization in 7 and partial recanalization in 7 cases. No imaging was available for the remaining 4 patients. Conclusions The incidence of CSVT in children with ALL was approximately 2%. No statistically significant clinical predictors for CSVT were identified. The mortality related to CSVT was 10%. Anticoagulation with LMWH was the treatment of choice in most cased and was well tolerated. Disclosures No relevant conflicts of interest to declare.
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  • 9
    Publikationsdatum: 2014-12-06
    Beschreibung: Introduction: Busulfan (Bu) is used in the conditioning regimen for hematopoietic stem cell transplantation (HSCT). Therapeutic drug monitoring (TDM) of Bu with subsequents adjustments doses based on a “target” therapeutic concentration may reduce toxicity after HSCT. Objectives: To evaluatethe impact of TDM of Bu and clinical outcomes in patients with acute leukemia that underwent to allogeneic matched related donor (MRD) and allogeneic matched unrelated donor (MUD) HSCT. Patients and methods: From January 2009 to January 2014, we prospectively analyzed 42 patients with diagnosis of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) who underwent TDM of Bu (IV or oral) before transplantation (test dose) and TDM on 1st day of conditioning regimen. Samples were collected at 0, 30’, 60’ and subsequently every hour until 6 hours after administration of busulfan. The plasma was extracted by HPLC (High Performance Liquid Chromatography). All the patients that were submitted to TDM had a test dose 15 days to 48 hours before transplantion. The dose of Bu was adjusted during the first day of the conditioning regimen based on test dose. At the same time we analyzed 21 patients in the retrospective group who did not underwent TDM (from 2004 to 2010). Results: In the retrospective group (n=21), all of them underwent to MRD transplantation. Six (46.2%) were in first complete remission (CR1), 18(85.7%) patients received Bu and cyclophosphamide (BuCy) and the mean of age was 38 years (18-55 Yo). The median of CD34+ cells was 5.4 x 106/kg. The second group consisted by patients that received oral Bu (n= 21): 7 (33.3%) underwent to MUD transplantation, 14 (66.6%) to MRD transplantation, 8 (44.4%) patients were second complete remission (CR2), 4 (22.2%) had active disease status with a mean age of 32.7 years (14-58 Yo). Fifteen (71.4%) received BuCy and 16 (76.2%) received cells from peripheral blood. The median of CD34+ cells was 5.8 x106/kg. The median area under the curve (AUC) in 24 hours was 4950 μMol.min (3196.6- 8212 μMol.min). The third group was IV Bu (n= 21): 7 (33.3%) patients underwent MRD and 14 (66.6%) MUD transplantation, 7 (33.3%) patients were CR1, 7 (33.3%) had active disease or prior HSCT with a mean of age 52.7 years (20-74 Yo). The majority of patients received fludarabine and Bu (n=18; 85.7%) as conditioning and bone marrow was the main source. Immunosuppression was based on FK-506 and methotrexate (90.5% of patients). The median of AUC in 24 hours was 5690 μMol.min (3539.6- 8881.8 μMol.min). The cumulative incidence (CI) of sinusoidal obstructive syndrome (SOS) in the retrospective group and IV Bu were 9.5% for both, while in the group oral Bu it was at 19% (p = 0.566). The median AUC of Bu received during conditioning for those who died of SOS was lower in oral Bu than IV Bu (4872 uMol.min vs 5732 uMol.min respectively). The CI of acute graft-versus-host disease (aGVHD) at D+100 was 38.1% in the retrospective group, 40.6% in oral Bu and 42.9% in IV Bu. Chronic GVHD was 13.6% in oral Bu, 34% in IV Bu and 42.9% in the retrospective group (p = 0.142). The CI of relapse at D+100 was 19% in IV Bu, 4.8% in the retrospective group and oral Bu did not have this event. The IC of death at D+100 was 34.9% in group oral Bu, 9.5% in IV Bu and 14.3% in the retrospective (p = 0.102). The CI of relapse at 1.5 years was 35.8% in the IV Bu, 34.8% in oral Bu and 14.3% in the retrospective group. The CI of death at 1.5 years was 9.5% in group IV Bu, 53.5% in oral Bu and 34.3% in the retrospective (p = 0.015). Among patients who died until D+100, the median of AUC was 5732 μMol.min (5578.5-6818.5 μMol.min) during the conditioning for IV Bu and 4872 μMol.min (3448-8212 μMol.min) for oral Bu. The range between the AUC was large and there was no correlation with patients who died. Conclusion: In acute leukemia SOS had an impact on mortality at D+100 after HSCT (p
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  • 10
    Publikationsdatum: 2014-12-06
    Beschreibung: Introduction: The application of nanoparticles in dendritic cell (DC)-based cancer immunotherapy represents a promising strategy to enhance antigen-specific T cell immune responses. This study was to investigate the effect of bPEI-SPIONs on antigen-specific T cell responses elicited by DCs loaded with apoptotic U266 myeloma tumor antigen in the presence or absence of bPEI-SPIONs. Materials and Methods: The myeloma tumor antigens were prepared as following: 1) apoptotic U266 cells by UBV-irradiation and overnight incubation (16 h irradiated cells) and 2) apoptotic U266 cells by UVB-irradiation and 2 h incubation in the absence (2 h irradiated cells) or 3) presence of bPEI-SPIONs (bPEI-SPION 2 h irradiated cells). Monocyte-derived immature DCs were activated with TNF-α, loaded with several kinds of myeloma tumor antigens 2 h after TNF-α stimulation, and cultured for 2 days. Results: Optimal concentration of bPEI-SPIONs was 16 µg/mL to uptake into tumor cells and the bPEI-SPIONs render U266 cells sensitive to UVB-irradiation through reactive oxygen species (ROS) induction pathway hence accelerated the apoptotic cell death. 2 h irradiated cells and bPEI-SPION 2 h irradiated cells released immunogenic proteins, including HSP70, HSP90, and HMGB1. bPEI-SPION 2 h irradiated cells were easily up-taken by DCs without alteration of surface phenotypes and migration capacities. DCs loaded with bPEI-SPION 2 h irradiated cells showed highest IL-12p70 production level and Th1 polarization compared to other DCs. Conclusion: These results suggest that bPEI-SPIONs are a promising tool to improve immunogenicity of myeloma tumor cells and to enhance Th1 polarization of DCs loaded with these tumor cells. Disclosures No relevant conflicts of interest to declare.
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