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  • American Society of Hematology  (5)
  • Zhang, Lingyan  (5)
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Verlag/Herausgeber
  • American Society of Hematology  (5)
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Erscheinungszeitraum
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  • 1
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 9544-9545
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2022
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 2
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5323-5323
    Kurzfassung: Introduction: B-cell non-Hodgkin lymphoma is the most frequent type of non-Hodgkin's lymphoma. RCHOP regimen is established as the standard therapy for aggressive and indolent B-cell NHL, which has a 10%-20% rate of febrile neutropenia (FN). Recently, pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) is frequently used in clinical practice. This randomized controlled clinical study was conducted to investigate the efficacy and safety of prophylactic PEG-rhG-CSF in patients with B-cell non-Hodgkin lymphoma on RCHOP chemotherapy. Methods:We included 162 patients with pathological diagnosis of B-cell non-Hodgkin lymphoma including diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma (MCL),from October 2016 to May 2019 at Shandong Provincial Hospital Affiliated to Shandong University. All patients gave written informed consent in accordance with the Declaration of Helsinki. The patients were randomized into PEG-rhG-CSF and rhG-CSF groups. Each patient received three cycles of chemotherapy with identical RCHOP regimens. In the study group, the patients received PEG-rhG-CSF 6mg(weight≥45Kg)or 3mg(weight≤45Kg)once 24 hours after the end of chemotherapy drugs of every chemotherapy cycle. In the control group, they weren't preventively administered rhG-CSF. If their neutrophil count (ANC)≤1.0×109/L, they were administered rhG-CSF:5ug/kg/day until their neutrophil count (ANC)≥2.0×109/L. The primary endpoint was the incidence of III/IV grade neutropenia and febrile neutropenia(FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application and safety were observed. Analyses were performed with SPSS Statistics 20.0 (IBM-SPSS, Chicago, Illinois). The numerical data was presented as mean ± SD. Statistical analysis was performed using one-way analysis of variance and chi-square test. A p-value 〈 0.05 was considered statistically significant. Results: Clinical characteristics for PEG-rhG-CSF and rhG-CSF groups were shown in Table1. There were no significant differences in age, gender,height, body weight, body mass index, Ann Arbor and IPI staging. The incidence of IV grade neutropenia during cycle 1 in 81 evaluable study cycles and 81 evaluable control cycles were 7.41% and 35.80%( P 〈 0.01), with durations of 2.85±0.62 days and 3.11±1.23 days (P 〉 0.05). The differences in I/II/III grade neutropenia between study and control groups weren't statistically significant (Table2,Fig.1). After secondary prophylactic use of PEG-rhG-CSF In the study group, the incidences of III/IV grade neutropenia decreased from 77.78% to 14.81% (P 〈 0.01).Statistically significant differences were observed in the incidences of FN (12.35% and 34.57% for the PEG-rhG-CSF and rhG-CSF groups, respectively; P 〈 0.01) and in the proportion of patients who received antibiotic therapy (11.11% and 37.04%, respectively; P 〈 0.01) during cycle 1(Table2,Fig .2). The safety profiles of PEG-rhG-CSF and rhG-CSF were similar. Bone pain occurred in 7.41% of the cases during the study cycles and 2.47% in the control cycles (P 〉 0.05 ), which were mostly mild or moderate. Patients receiving PEG-rhG-CSF who developed III/IV grade neutropenia were significantly older than those without neutropenia (53.41±14.96 vs. 63.64±4.65;years; p=0.01) (Fig.3).The incidence of III/IV grade neutropenia in patients older than 60 years was significantly higher than that in patients younger than 60 years(24.44% vs. 6.38%; P =0.038). Conclusions: Prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade III/IV neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve prognosis. III/IV grade neutropenia after prophylactic use of PEG-rhG-CSF were more likely to occur in patients older than 60 years. After the use of PEG-rhG-CSF, the elderly patients should be pay more attention to them. Disclosures No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2019
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 3
    Online-Ressource
    Online-Ressource
    American Society of Hematology ; 2020
    In:  Blood Vol. 136, No. Supplement 1 ( 2020-11-5), p. 49-49
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 49-49
    Kurzfassung: Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic strategy to cure a large number of hematologic diseases. Acute graft-versus-host disease (aGVHD) remains a major obstacle against long-term survival for patient underwent allo-HSCT. Oxidative stress can generate large amounts of oxygen free radicals affecting the metabolism, proliferation, and differentiation of normal cells. It may also further induce the autoimmune response to form a waterfall effect, causing reversible to extracellular insults. It has been confirmed that oxidative stress plays an important role in the pathogenesis of aGVHD and the following organ injury. Multiple immunosuppressant agents including calmodulin inhibitor, corticosteroids, anti-CD25 antibody, and JAK1/JAK2 inhibitors have been used to treat GVHD in clinical scenarios. However, quite an amount of patients will develop to glucocorticoid-refractory aGVHD and too intensive immunosuppressive therapy will increase the incidence of infection and malignancy relapse. Nrf2/HO-1 (Nuclear factor E2-related factor 2/ Haemoxygenase-1) signaling pathway has been recognized as a major regulator against oxidative stress injury. Recent studies have demonstrated that hyperbaric oxygen therapy (HBOT) significantly improved non-healing ulcers secondary to GVHD and hemorrhagic cystitis after HLA-mismatched allo-HSCT whether induced by infection or aGVHD. Based on the important role of oxidative stress in the process of aGVHD, we hypothesis that HBOT can improve aGVHD via up-regulating Nrf2/HO-1 pathway. Methods: By using an allo-HSCT murine model of C57BL/6 (H-2KB)→BALB/C (H-2KD), we evaluated the therapeutic effects of HBO on aGVHD. The murine model of aGVHD was established in BALB/C mice by lethally body irradiation, followed by 1×107 bone marrow cells and 2×107 spleen cell transplantation. Mice were randomly divided into three groups: BMT+HBO group, GVHD group, and GVHD+HBO group. BMT+HBO group and GVHD+HBO group mice were simultaneously treated with HBO per day for 2 weeks from day -7 to +7 before- to post stem cell transfusion. The HBO therapy was performed for mice in a sealed chamber at a pressure of 2.4 atmosphere absolute (ATA) for 90 min per day. The induction of the murine GVHD process and GVHD scores were calculated according to the method of Cooke et al (1996) every 6 days. Results: The flow cytometry showed that the level of H-2KB positive cells in the bone marrow cavity of the recipient mice was more than 95%, indicating successful implantation (Figure A). The BALB/C recipient mice in the control group (non-HBOT) showed typical aGVHD symptoms within 20 days, mainly including wasting, ruffled fur, hunched back, skin defect, ocular signs, diarrhea, and anal swelling (Figure B). The aGVHD+HBO group only showed slightly ruffled fur on 40 days post-transplantation (Figure C) and the aGVHD score of aGVHD+HBO group was much lower than that of GVHD group (Figure D) Weight loss was mild in the aGVHD+HBO group than that in the aGVHD group (Figure E). All aGVHD group mice eventually succumbed within 1 month after transplantation, the survival was shorter than that of aGVHD+HBO group. The survival time was analyzed by Kaplan-Meier method (Figure F). The BMT+HBO group served as a control for HBO toxicity. Immunofluorescence microscopy evaluation of mouse liver, skin, and small intestine revealed an attenuation of fluorescence signal in the aGVHD+HBO group, indicating HBO can significantly reduce ROS levels (Figure G). Immunohistochemical staining showed that the expression of NRF2 protein in the liver collected in day 16 post-transplantation was higher than the BMT+HBO group and aGVHD group (Figure H). Conclusions: By using this murine model of aGVHD following allo-HSCT, our results indicated that ROS inhibition by HBOT markedly reduced the infiltration of inflammatory cells and tissue damage to targeted organs, resulting in significantly improved symptoms and prolonged survival. In conclusion, our study provided laboratory evidence that HBO can prevent and treat aGVHD by upregulating the expression of NRF2 and HO-1. HBOT might be a promising prophylactic and pre-emptive treatment choice for aGVHD. In the future, we will further investigate the accurate mechanism of HOBT in the process of aGVHD via Nrf2/HO-1 pathway, verify our preliminary animal experimental results in clinical application. Figure Disclosures No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2020
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 4
    Online-Ressource
    Online-Ressource
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5339-5339
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5339-5339
    Kurzfassung: Background: According to the 2016 revised World Health Organization (WHO) Classification of Lymphoid Tumors, high grade B-cell lymphoma (HGBL) has been delimited as a new category with two subgroups: HGBL with rearrangements of MYC and BCL2 and/or BCL6 (so-called "double/triple hit lymphoma), and HGBL-NOS (HGBLs with features intermediate between DLBCL and Burkitt lymphoma). Retrospective data indicated many patients with HGBL diagnosed at an advanced stage and often have extremely poor outcome even if they received intensive chemotherapy. The accurate genetic and pathological mechanism of this high-risk lymphoma remains uncertain. For HGBL, traditional scoring may not be systematic enough and has limited reference value, more accurate prognostic grouping indicators are needed. The aim of this study was to evaluate the clinicopathological significances in newly diagnosed HGBL and DLBCL. Several clinical and hematological indexes in concert with Fluorescence in situ hybridization (FISH) rearrangement and Immunohistochemistry (IHC) expression profiles of biomarkers between HGBL and DLBCL will also be analyzed. Methods: We reviewed 52 patients diagnosed as HGBL or DLBCL in our hospital from 2017 to 2018 retrospectively. The clinical and hematological characteristics of the patients including age, gender, Ann-Arbor stage, B symptoms, serum LDH levels, β2-microglobulin (β2-MG), peripheral EBV-DNA copies, white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and IPI score were collected. FISH detection was done in each patient to identify whether the patient had MYC, BCL2, and BCL6 rearrangement. The expressions of the above three indexes were done by IHC as well. NLR (neutrophil to lymphocyte ratio) was definited as ANC/ALC ratio. Results: A total of 52 newly diagnosed patients were included in this study, including 34 (65.4%) males and 18 (34.6%) females. The median age at diagnosis was 54.1 years old (range, 15-88 years), and 22 (42.3%) of them were more than 60 years old. Six patients were classified into the HGBL category and 2 of them were HGBL-NOS subgroup. Twenty-five patients were MYC, BCL2, or BCL6 rearrangement single-positive. Among them, MYC, BCL2, and BCL6 rearrangement were detected in 13.5%, 7.7%, and 30.8% of 52 patients respectively.MYC (cut-off value 〉 40%), BCL2 (cut-off value 〉 50%), and BCL6 expression was found in 48.1%, 50%, and 65.4% of 52 patients, respectively. Among all of the patients, 32.7% (17/52) CD5 positive and 73.1% (38/52) MUM1 positive. 30.8% (16/52) of them were at stage Ⅰ/Ⅱ and 69.2% (36/52) of them were at stage Ⅲ/Ⅳ. 53.8% (28/52) of the patients had a high blood LDH level, 26.9% (14/52) showed an elevation of β2-MG level ( 〉 3mg/L) and 38.5% (20/52) presented high IPI score (IPI 〉 2). The baseline clinical, hematological, and pathological characteristics are described in Table 1, 2. 3. With Pearson's Chi-square Tests analysis, the IPI score was significantly higher in patients older than 60 years old (P 〈 01). Patients with the rearrangement of both BCL2 and BCL6 as well as CD5+ tend to have a higher Ki 67 ratio (P=0.045) and the same thing happened to patients with both MYC and BCL6 expression (P=0.049). By the combination of either a positive gene rearrangement or a positive IHC marker (CD5 or MUM 1), there was a close association between any of the above with high β2-MG (P=0.024) and pheripheral EBV DNA copoies (P=0.012). Besides, the triple positive rearrangements combined with CD5 positive is associated with a higher NLR (P=0.027). Conclusions: In this study, we validated the prognostic value of several clinical, hematological, genetic, and pathological indexes in newly diagnosed HGBL and DLBCL. We found that if there's only one rearrangement gene or IHC marker (CD5 or MUM 1) positive, there was no significant difference between these alterations and some classic evaluation indexes such as serum LDH and Ann-Arbor stage. Patients with BCL2 + BCL6, or MYC + BCL6, or triple positive arrangement might have a more aggressive disease progression if positive CD5 expression could be detected at the same time. In the future, we plan to further evaluate if NLR has any correlation with the clinical outcome of patients with double-/triple-hit lymphomas or double-/triple expression lymphomas. More data from larger patient subset are needed to corroborate these findings. Disclosures No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2019
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 5
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 2-3
    Kurzfassung: Introduction: CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is characterized by a poor prognosis, poorly respond to the regulatory treatment strategy, and a relatively high incidence of central nervous system (CNS) infiltration. In this study, we aim to identify key differentially expressed miRNAs (DE-miRNAs) and their target genes in the peripheral blood of CD5+ refractory and relapsed (CD5+ R/R DLBCL) patients. The relationship of the DE-miRNAs and the pathogenesis of CD5+ R/R DLBCL will also be analyzed by bioinformatics tools. Methods: Three female patients with confirmed CD5+ R/R DLBCL were enrolled in this study, their age were 38, 62 and 65 years old, respectively. Three healthy female adults aged 42, 55 and 61, respectively were selected as the control group. The peripheral venous blood of them was collected for RNA extraction and standard small RNA sequencing. Differentially expressed miRNAs analysis was performed with R package edgeR. The target genes of DE-miRNAs were predicted by miRNet. A protein protein interaction (PPI) network was established for these target genes through string database. Functional annotation and pathway enrichment analyses for the target genes were performed through DAVID database to identify their potential functions, target genes, and pathways they might be involved in. Results: 1. Scatter plots, Volcano plots and Heat-maps were used to visualize miRNAs of Differentially expressed genes. As shown in Fig.1, Fig. 2 and Fig. 3. 2. Fifty-five sequences were significantly upregulated and 23 were significantly downregulated in patients with CD5+ R/R DLBCL.Among the candidate miRNAs, 11 up-regulated genes and 4 down-regulated genes were selected according to the log2FC value. The target genes of 11 potential up-regulated and 4 down-regulated DE-miRNAs were successively predicted by As shown in Table 1, a total of 439 and 632 predicted targets of the up-regulated and down-regulated DE-miRNAs were identified, respectively. 3. PPI networks of predicted target genes of 11 upregulated DE-miRNAs (Fig.4a) and 4 downregulated DE-miRNAs (Fig. 4b) were separately constructed using the STRING database and Cytoscape software. According to a degree, the top 10 hub genes in the networks were screened out and were listed inTable 2. Six important hub genes were identified, including two target genes predicted by up-regulating DE-miRNAs, namely NRAS and PIK3R1, and four target genes predicted by down-regulating DE-miRNAs, namely EGFR, VEGFA, IGF1 and Grb2. 4. DAVID now provides a comprehensive set of functional annotation tools for investigators to understand biological meaning. GO analysis was divided into three functional groups, including molecular function (MF), biological processes (BP), and cell composition (CC). The top 10 GO terms of targets of up-regulated DE-miRNAs were presented in Fig.5a-c. The top 10 GO terms of targets of down-regulated DE-miRNAs were shown in Fig. 5d-f. 5. Based on the KEGG database, we analyzed the pathways in which the differentially expressed target genes were involved in. As shown in Fig. 6a-b. The targets of up-regulated DE-miRNAs were enriched in pathways in cancer, oxytocin signaling pathway, ErbB signaling pathway, Rap1 signaling pathway, and proteoglycans in cancer. Whereas the targets of down-regulated DE-miRNAs were enriched in pathways in cancer, Ras signaling pathway, and PI3K-Akt signaling pathway. Conclusions: In this study, we analyzed the differentially expressed miRNAs in CD5+ R/R DLBCL patients, identified their potential functions, target genes, and pathways they might be involved in. This study found that ErbB signaling pathway, Rap1 signaling pathway, Ras signaling pathway and PI3K Akt signaling pathway were the most frequently involved pathways of miRNAs related genes. Target genes including NRAS, PIK3R1, EGFR, VEGFA, IGF1, and Grb2 might have a close relationship in the pathogenesis of CD5+ R/R DLBCL. New targeted drugs related to these pathways and genes may be beneficial to the treatment of CD5+ DLBCL. Our preliminary informatic results might be helpful to deeply understand the pathogenesis and chemotherapy resistance mechanism of CD5+ R/R DLBCL. In the future, we will verify our preliminary informatic results in pathological tissues from patients with CD5+ DLBCL in larger samples. Disclosures No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2020
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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