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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-06-13)
    Abstract: Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein  〈  0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87] ), along with eGFR (per 30 mL/min/1.73 m 2 : 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m 2 ) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR ( 〈  60 mL/min/1.73 m 2 ) and high albumin concentration ( 〉  1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 2
    In: Journal of Nephrology, Springer Science and Business Media LLC, Vol. 35, No. 4 ( 2022-05), p. 1135-1144
    Type of Medium: Online Resource
    ISSN: 1724-6059
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1475007-7
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  • 3
    Online Resource
    Online Resource
    The Japan Institute of Marine Engineering ; 2003
    In:  Journal of The Japan Institute of Marine Engineering Vol. 38, No. 5 ( 2003), p. 292-297
    In: Journal of The Japan Institute of Marine Engineering, The Japan Institute of Marine Engineering, Vol. 38, No. 5 ( 2003), p. 292-297
    Type of Medium: Online Resource
    ISSN: 1346-1427 , 1884-3778
    Uniform Title: FCD材引け巣へのHIP処理の効果
    Language: Japanese
    Publisher: The Japan Institute of Marine Engineering
    Publication Date: 2003
    detail.hit.zdb_id: 2939000-X
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  • 4
    In: Marine Engineering, The Japan Institute of Marine Engineering, Vol. 45, No. 4 ( 2010), p. 488-499
    Type of Medium: Online Resource
    ISSN: 1346-1427 , 1884-3778
    Uniform Title: 2009年における各研究委員会の活動
    Language: English , Japanese
    Publisher: The Japan Institute of Marine Engineering
    Publication Date: 2010
    detail.hit.zdb_id: 2939000-X
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  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2910-2910
    Abstract: Background: The number of solid organ transplantation (SOT) is increasing. While the remarkable improvement in SOT procedures provides recipients with a good chance of long-term survival, the prolonged immunosuppression has led toa variety of malignancies in solid organ transplant (SOT) recipients; post-transplant lymphoproliferative disorder (PTLD) is a life-threating complication among them. However, there remain some controversies regarding its clinical features. Method: We retrospectively surveyed the patients who had visited both departments: hematology and urology, or renal surgery in kidney center at Tokyo Women's Medical University Hospital from 2003 to 2017. We identified 61 patients diagnosed with hematological disorder in kidney-transplant recipients. Among them, PTLD were analyzed. Continuous variables were compared using Student's t-tests. Overall survival rate (OS) was calculated using the Kaplan-Meier method. P values 〈 0.05 were considered significant. Statistical analyses were performed using JMP Pro 14 (SAS Institute Inc., Cary, NC, USA) and GraphPadPrism version 7.0 (GraphPad Software, San Diego, USA). This study was conducted in accordance with the Declaration of Helsinki and approved by the institutional review boards. Results: During the survey period, 3,133 patients had visited both departments: hematology and urology, or surgery in Kidney Center. Among them, 61 kidney-transplant recipients were diagnosed with hematological disorder; they comprised 27 PTLD, 10 plasmacytic disorder, 6 idiopathic thrombocytopenic purpura, 5 myelodysplastic syndromes, 4 acute leukemia, 3 polycythemia, 6 other diseases. Among the patients with PTLD (n = 27), 18 patients (66.7%) were male.Median patient ages at the diagnosis of PTLD and kidney transplant were 54 (25-79) and 43 (16-75) years, respectively. Eighteen and nine patients had received kidney-transplant from a living donor (15 related and three unrelated donors) and a cadaveric donor, respectively. The median time from kidney transplant to diagnosis of PTLD was 7.8 years; there was a significant difference in the time between the kidney-transplant recipients from a cadaveric donor and those from a living donor (Figure 1A, 11.3 and 5.6 years, P = 0.02). With regard to the histological subtypes of PTLD, they comprised 17 diffuse large B-cell lymphoma (63.0%), 2 Burkitt lymphoma (7.4%), 4 unclassified B-cell lymphoma (14.8%), 2 T-cell lymphoma (7.4%), and 2 unknown cases (7.4%). 24 of 27 patients had extranodal involvement: 9 central nervous system (33.3%), 7 gastrointestinal tract (25.9%) and other sites. First-line treatment procedure which all patients received was the modification of immunosupressants; complete response (CR) rate was 37.0%. After the failure of first-line therapy, 15 of 27 patients received chemotherapy: 4 rituximab monotherapy (30.8%), 6 CHOP-like regimens (46.2%), and other regimens (33.3%). Among them, five patients experienced relapse. They received salvage chemotherapy, and 2 and one patients achieved CR and partial response, respectively. Rest of them died of lymphoma and infection. The estimated five-year OS from the diagnosis of PTLD and the initiation of chemotherapy was 88.7% and 86.7%, respectively. During the survey period, 5 patients died; their causes of death were 3 lymphomas, 1 infection, and 1 heart failure. There were no deaths in kidney-transplant recipients from a cadaveric donor (Figure 1B). Discussion: While our cohort had more extranodal PTLD recipients than those reported previously, the modification of immunosupressants improved them in more than one-third of cases, which showed the usefulness of it as first-line treatment procedure for PTLD. Nearly half of cases were identified in recipients from a cadaveric donor; the results suggest that the incidence o PTLD among them is higher than those from a living donor because the number of kidney-transplant from a living donor was 10 times higher than those from a cadaveric donor. This study has several limitations due to its retrospective nature and small sample size. In addition, the estimated five-year OS might be better than actual because some patients became lost to follow-up. Further large-scale studies are warranted to validate the findings of this study. Disclosures Hagiwara: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Tanaka:Bristol-Myers Squibb: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 6
    Online Resource
    Online Resource
    Wiley ; 2004
    In:  Journal of Polymer Science Part B: Polymer Physics Vol. 42, No. 12 ( 2004-06-15), p. 2407-2418
    In: Journal of Polymer Science Part B: Polymer Physics, Wiley, Vol. 42, No. 12 ( 2004-06-15), p. 2407-2418
    Type of Medium: Online Resource
    ISSN: 0887-6266 , 1099-0488
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2004
    detail.hit.zdb_id: 1473448-5
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  • 7
    In: British Journal of Haematology, Wiley, Vol. 186, No. 6 ( 2019-09)
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1475751-5
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  • 8
    In: Clinical and Experimental Nephrology, Springer Science and Business Media LLC, Vol. 27, No. 5 ( 2023-05), p. 480-489
    Type of Medium: Online Resource
    ISSN: 1342-1751 , 1437-7799
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1499111-1
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  • 9
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5219-5219
    Abstract: Background: Methotrexate-associated lymphoproliferative disorders (MTX-LPD) develops in patients with rheumatoid arthritis (RA) or other autoimmune disorders during low-dose MTX treatment. MTX-LPD includes wide variety disease spectrum, ranging from polymorphic proliferation to aggressive lymphoma. Although etiology of MTX-LPD has not been fully understood, approximately half of the MTX-LPD cases showed association with EB virus (EBV), suggesting that MTX treatment causes reduced immune response to EBV-positive cells, and results in MTX-LPD development. Natural killer (NK) cells play important roles in eradicating tumor and virus-infected cells. NK cell function is modulated by multiple cell surface receptors, including Killer immunoglobulin-like receptor (KIR). There are multiple KIR genes (inhibitory or activated), which are various in number and/or composition among individuals, on chromosome 19q. Previous reports demonstrated that combination of KIR genes affects NK cell function, and is associated with the risk of development of certain types of cancers, viral infections and collagen disease. There is no report about the association of KIR genotype and MTX-LPD. We consider that NK cells play a significant role in suppression of MTX-LPD development. In this study, we focused on examining genotype KIR and KIR-ligand (HLA class I). Methods: We retrospectively analyzed 35 MTX-LPD cases diagnosed between 2009 and 2019. Genomic DNA was extracted from mononuclear cells that were isolated from the bone marrow or peripheral blood samples of patients with MTX-LPD. KIR genotypes were analyzed using the KIR genotyping sequence-specific primers kit. The variations of KIR content and haplotype and their relationship with progression to malignant lymphoma (ML) and response to chemotherapy were investigated. HLA was analyzed using PCR-Luminex assay. The frequency of each HLA allele and each combination was determined by referring to the data base of an HLA laboratory. Chi-squared (χ2) tests and Wilcoxon rank sum tests were used to test associations between the variables. Results: Among the 35 patients, 25 were diagnosed with ML and 10 with polymorphic LPD. Diffuse large B cell lymphoma (DLBCL) was most common type in ML (57.7%). Table 1 showed characteristics of patients and summary of the results. All patients underwent MTX treatment for RA. The median duration of MTX administration at the time of MTX-LPD diagnosis is 11.5 years (range=0.8-27.2), and median MTX dose was 10mg/week (range=4-17.6). The duration and dose of MTX had no effect between ML and polymorphic LPD. Twenty-three patients required chemotherapy, and 12 patients had tumor regression after stopping MTX treatment. Relative patient populations requiring chemotherapy in ML or polymorphic LPD were 85% or 11%, respectively (P=0.0001). EBV-positive patients tended to regress tumors with MTX discontinuation alone (P=0.16). In KIR genotype analysis, patterns of number and combination of the KIR genes are mainly classified as haplotype "A" containing multiple inhibitory KIR genes with a KIR 2DS4 (an activated KIR [aKIR]) and haplotype "B" (other than haplotype "A"). Patients were classified in haplotype A (13 cases, 37%) and haplotype B (22 cases, 63%), respectively. ML patients showed higher ratio in haplotype A (ML 46.2% vs LPD 11.1% P=0.045). There was no difference in number of aKIR or iKIR between ML and polymorphic LPD patients. In HLA Class I analyses, there was significant difference in frequencies of HLA-C haplotype between lymphoma and polymorphic LPD patients (P=0.026). Furthermore, HLA- C1 / C1 patients were more relapsed or refractory to chemotherapy than C1 / C2 patients (P = 0.17). Conclusion: This is the first report showing clinical significance of KIR genotypes in MTX-LPD. Patients with haplotype A, a suppressive haplotype, seems to be at high risk for developing lymphomas that require chemotherapy during MTX treatment. HLA- C1/C1 patients are more likely to develop lymphomas that respond poorly to treatment, suggesting that the activity of NK cells may be lower because ligands can match with KIRs that are more restricted than C1/C2. Considering the potential NK functions with KIR genotype would improve the understanding of the prognosis and lead to prevention for MTX-LPD. Disclosures Hagiwara: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Harigai:Bristol Myers Squibb Co: Other: personal fees, Research Funding; Eisai Co: Other: personal fees, Research Funding; Ayumi Pharmaceutical Co: Other: personal fees, Research Funding; AbbVie Japan GK,: Other: personal fees, Research Funding; Eli Lilly Japan K.K: Other: personal fees; Kissei Pharmaceutical Co.: Other: personal fees; Teijin Pharma Ltd: Other: personal fees, Research Funding; Mitsubishi Tanabe Pharma Co: Research Funding; Nippon Kayaku Co.: Research Funding; Pfizer Japan Inc.: Other: personal fees; Chugai Pharmaceutical Co., Ltd.: Other: personal fees; Japan College of Rheumatology: Other: personal fees; Boehringer Ingelheim Japan, Inc: Other: personal fees; GlaxoSmithKline K.K: Other: personal fees; Oxford Immuotec,: Other: personal fees. Tanaka:Bristol-Myers Squibb: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3133-3133
    Abstract: Recent advances of monoclonal antibodies provide a potent anti-myeloma effect based on antibody-dependent cytotoxicity (ADCC). Elotuzumab is a monoclonal antibody which binds SLAMF7 on the surface of myeloma cells and induces ADCC by NK cells (Cancer Immunol Immunother 64:61-73,2015). Lenalidomide may enhance the killing activity ad IFN-gamma production in NK cells (Blood 126:50-60,2015). In Eloquent-2 trial, the combination therapy of Elotuzumab, Lenalidomide, and Dexamethasone (ELD) showed a significant relative reduction in the risk of disease progression or death (N Engl J Med 373:621-631,2015). However, the number of NK cells in patients with multiple myeloma is generally suppressed, and the activity is often exhausted (Cytometry 26:121-124,1996, Med Oncol 24:312-317,2007). It is unclear if they fully exhibit the ADCC against myeloma cells. Also, enough number of NK cells as effector cells is required to obtain effective ADCC. To enhance the ADCC activity of NK cells against multiple myeloma, cell therapy using expanded NK cells might be effective. Therefore, we conduct the clinical trial of ex-vivo expanded NK cell infusion therapy in combination with ELD for minimal residual disease (MRD) after autologous stem cell transplantation (ASCT). Clinical trial registry number: UMIN000033128 Study design: Non-randomized single-arm phase I/ II clinical trial. Study population: 20; Five for phase I part and 15 for phase II. Primary endpoint: Any grade of adverse events, and the response defined by IMWG criteria. Secondary endpoint: Overall survival, progression-free survival, and MRD. Study protocol: 1x106 - 5x107/kg of ex-vivo expanded NK cells are infused on day 2 of ELD regimen in patients who failed to achieve sCR or with detective MRD after ASCT. The NK cell infusion with ELD therapy will be repeated 4 cycles monthly. Major inclusion criteria: (1)Multiple myeloma diagnosed by IMWG diagnostic criteria, (2)Age: 20= 〈 , 65 〉 =, (3)ECOG Performance status0-2, (4)PR or better after induction therapy, (5) Transplant eligible patients without severe organ damages, (6)Patients failed to achieve sCR after stem cell transplantation or positive for minimal residual disease by 6-8 color Flow cytometry. Major exclusion criteria: (1) Patients who were previously transplanted, (2) Failed to obtain more than 2x106/kg of CD34+ cells, (3) Patients who are not eligible for harvest or transplant due to cardiac or pulmonary disorder, AST/ALT/total bilirubin 〉 2.5x lower limit, serum Cr 〉 =2.0mg/dl, (4) Patients who have severe allergy or uncontrollable active infection. Currently, two participants completed the protocol and are under the observation. Figure Disclosures Hagiwara: Bristol-Myers Squibb: Research Funding. Kanno:Agios Pharmaceuticals, Inc.: Honoraria. Tanaka:Bristol-Myers Squibb: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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