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  • 1
    In: Oncotarget, Impact Journals, LLC, Vol. 8, No. 23 ( 2017-06-06), p. 37605-37618
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2560162-3
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  • 2
    In: Acta Haematologica, S. Karger AG, Vol. 140, No. 3 ( 2018), p. 146-156
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 The neutrophil-to-lymphocyte ratio (NLR) is an independent prognostic marker in solid and hematological cancers. While the derived NLR (dNLR) was shown to be non-inferior to the NLR in large cohorts of patients with different cancer types, it has not been validated as a prognostic marker for multiple myeloma (MM) to date. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Between May 22, 2011 and May 29, 2014, 176 patients with MM from 38 centers who were ineligible for autologous stem cell transplantation were analyzed. The dNLR was calculated using complete blood count differential data. The optimal dNLR cut-off value according to receiver operating characteristic analysis of overall survival (OS) was 1.51. All patients were treated with melphalan and prednisone combined with bortezomib. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The complete response rate was lower in the high dNLR group compared to the low dNLR group (7 vs. 26.1%, respectively; 〈 i 〉 p 〈 /i 〉  = 0.0148); the corresponding 2-year OS rates were 72.2 and 84.7%, respectively ( 〈 i 〉 p 〈 /i 〉  = 0.0354). A high dNLR was an independent poor prognostic factor for OS (hazard ratio 2.217, 95% CI 1.015–4.842; 〈 i 〉 p 〈 /i 〉  = 0.0458). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The dNLR is a readily available and cheaply obtained parameter in clinical studies, and shows considerable potential as a new prognostic marker for transplantation-ineligible patients with MM.
    Type of Medium: Online Resource
    ISSN: 0001-5792 , 1421-9662
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2018
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  • 3
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1151-1151
    Abstract: Abstract 1151 Poster Board I-173 Introduction The mainstay of treatment for chronic graft-versus-host disease (GVHD) is steroid. However, there is limited treatment option for steroid-refractory chronic GVHD. Although the pathogenesis of chronic GVHD is still uncertain, the possible relation of auto-antibodies with chronic GVHD (Patriarca F, et al. Exp Hematol 389-96, 2006) and the result from a previous pilot study (Cutler C, et al. Blood 756-762, 2006) suggested that a treatment strategy targeting against B cells might become another effective therapy for chronic GVHD. Thus, we performed a study to determine the efficacy of rituximab (Mabthera®, Roche), an anti-CD20 monoclonal chimeric antibody in patients with steroid-refractory chronic GVHD. Patients and methods This is a multicenter, open-labeled prospective phase II study performed by the Korean Society of Blood and Marrow Transplantation (NCT00472225). Patients should be diagnosed as chronic GVHD according to the criteria for clinical trials in chronic GVHD proposed by National Institutes of Health Consensus Development Project (Filipovich AH, et al. Biol Blood Marrow Transplant 945-56, 2005). The steroid-refractoriness was defined as the same severity during the last one month while patients received the equivalent of prednisone ≥0.5mg/kg per day or 1mg/kg every other day at least for 30 days or longer. The treatment schedule consists of induction (rituximab 375mg/m2 weekly IV for 4 consecutive weeks) and maintenance (rituximab 375mg/m2 monthly IV for 4 consecutive months). The response and the quality of life (SF36 questionnaire) were evaluated during the follow-up. Results 37 patients (20 male, 17 female) were evaluated, and their median age was 29 years (range 8-57 years, 7 patients from pediatrics and 30 from internal medicine). The time interval between transplantation and rituximab treatment was from 4.0 to 45.7 months. The most commonly involved organs were skin, oral cavity, eyes and lungs. The average number of involved organ per each patient was three and their average severity was grade 2-3. The median potential follow-up was 12.3 months (95% confidence interval: 12.06-12.54 months). The maximum response during follow-up was as follows: 8 complete response (21.6%), 22 partial response (59.5%), 6 no response (16.2%), and 1 disease progression (2.7%). Thus, the overall response rate was 81.1%. The dosage of steroid was reduced in all responders including complete withdrawal of steroid. The quality of life was improved in terms of physical health and mental/emotional health after treatment. However, 5 responders showed the progression of disease activity during follow-up, and infectious complications were life-threatening, thus, 8 patients died due to infections including pneumonia. The involvement of skin and oral cavity showed better response than the involvement of lungs and eyes. Conclusion The weekly administration of rituximab followed by monthly maintenance rituximab may be an effective treatment for steroid-refractory chronic GVHD, however, the active prophylaxis against infection should be considered. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 4
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4372-4372
    Abstract: 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.
    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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  • 5
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5379-5379
    Abstract: VMP regimen for newly diagnosed myeloma patients is well-documented treatment. However patients in real practice generally have worse performance status and less attention than those in clinical trials. Thus we conducted observational study to evaluate the efficacy and toxicity of VMP treatment in newly diagnosed Korean myeloma patients. Patients and Methods Data were prospectively collected from 39 hospitals. One hundred seventy three patients who started VMP as first line from 2011 May to 2012 April were included for analysis. Results Median age was 71 and 22.5% were more than 75 years old. Fifty-seven per cent were male sex. IgG type was most common (61.9%) and IgA 24.9%. ISS stage I was 13.8% and III was 51.5%. Patients with high risk FISH (Del17p, t(4;14), and t(4;16)) were 4.1%, 4.1%, and 2.3% respectively. Dose and schedule was followed original VISTA trial except for use of prednisolone instead of prednisone. Median 5cycles (range 1-9) were given and 105 patients stopped in the course of treatment. Most common cause were adverse event (28.8%) followed by disease progression or no response (19.6%). Twenty-five mortality cases were reported and 22 were in the course of treatment. The most common cause of mortality was infection (61%) followed by disease progression (13%). Overall response rate was 72.3% and response more than VGPR was 37.6%. Median progression free survival is 455 days and median OS was 504 days. One year PFS was 80.9 % and one year OS was 83.4%. Most common toxicity was cytopenia, peripheral neuropathy, and gastrointestinal toxicities such as nausea and diarrhea. Peripheral neuropathy of all grade and grade 3 or more was 58.6% and 6.36%, respectively Discussions Even though patients with higher proportion of ISS stage, efficacy of VMP regimen was considerable in Korean patients. With relatively high mortality due to infection in the course of treatment prophylactic measures for infection need to be developed. To reduce the incidence of peripheral neuropathy, close observation and intervention are needed to prevent aggravation of neuropathy. Disclosures: Off Label Use: lenalidomide in newly diagnosed myeloma. Kwak:celgene: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
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  • 6
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5184-5184
    Abstract: Introduction: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) generally offers improved outcomes compared with conventional chemotherapy in patients with multiple myeloma. The disease status before ASCT such as the achievement of complete response (CR) was also reported as an important prognostic factor in multiple myeloma. Thus, the type and efficacy of induction therapy could affect the treatment outcome of ASCT because these induction chemotherapy regimens are designed to reduce myeloma burden leading to CR before ASCT. A combination chemotherapy regimen, VAD consisting of vincristine, doxorubicin, and dexamethasone is the induction therapy regimen which has been used for a log time. However, many new induction regimens have been used including thalidomide plus dexamethasone, and bortezomib since their efficacy was proven for relapsed or refractory multiple myeloma. However, the efficacy of these new induction therapy regimens and their effects on outcomes of ASCT has rarely been compared to VAD induction therapy. Methods: We performed a retrospective multicenter analysis supported by the Korean Multiple Myeloma Working Party (KMMWP). We have compared the efficacy of induction therapy regimens including VAD chemotherapy, thalidomide-based induction therapy, bortezomib-containing induction therapy, cyclophosphamide-based therapy. We also assessed the effects of these induction therapies on the outcome of ASCT in terms of response, relapse after ASCT, and survival. Results: We analyzed 344 patients who received induction therapy followed by high-dose chemotherapy with single ASCT at 13 hospitals in Korea. Patients who received tandem ASCT or ASCT followed by allogeneic stem cell transplantation were excluded. Their median age at diagnosis was 55 year old (range 20–72). The most common immunophenotype was IgG kappa and lambda (103, and 63 respectively) while 72 patients had light chain disease (kappa 30, lambda 42). 241 patients (70.1%) received VAD chemotherapy as an induction therapy prior to ASCT, and 35 patients (10.2%) received thalidomide-based chemotherapy before ASCT including thalidomide with/without dexamethasone. 46 patients (13.4%) were exposed to bortezomib including bortezomib alone or combined with other agents such as bortezomib, doxorubicin, dexamethasone (PAD). 22 patients (6.4%) received cyclophosphamide-based induction therapy. Age, sex, stage (Durie-Salmon and International staging system), and immunophenotype were balanced among these four groups of patients. Complete response (CR) rate including nCR (near CR) of VAD chemotherapy was 20.3% (49/241). CR rate of bortezomib and thalidomide-based therapy was 43.5% (20/46), and 37.1% (13/35) respectively. Cyclophosphamide-based induction therapy induced 27.2% of CR (6/22). Thus, CR rate of bortezomib-based induction therapy was significantly higher than other regimens (P & lt; 0.05). There was no significant difference in the stem cell harvest and transplantation-related morbidity based on the type of induction therapy. The melphalan-based conditioning regimen was used in all patients, and the dosage of melphalan was from 100mg/m2 to 200mg/m2. There was no difference of conditioning regimen among the four groups. When we assessed the response after ASCT, the results were as follows: VAD group (48 patients with continued CR, 85 patients with induced CR, 55.2% of CR rate), Thalidomide group (20 patients with continued CR, 12 patients with induced CR, 60.0% of CR rate), Bortezomib group (20 patients with continued CR, 12 patients with induced CR, 69.6% of CR rate), and Cyclophosphamide group (5 patients with continued CR, 7 patients with induced CR, 54.5% of CR rate). There was no significant difference in the stem cell harvest and transplantation-related morbidity based on the type of induction therapy. Relapse rate after ASCT was lower in bortezomib group (34.8%) than VAD group (63.1%), cyclophosphamide group (63.6%), and thalidomide group (54.3%). However, there was no significant difference of overall survival among these four groups. Conclusions: Bortezomib-based induction therapy might be more effective for improving CR rate in patients who received single ASCT. A further prospective study should be warranted to confirm whether this augmented response rate with bortezomib-based induction therapy might be translated into survival benefits.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 7
    In: Oncotarget, Impact Journals, LLC, Vol. 8, No. 45 ( 2017-10-03), p. 79517-79526
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2560162-3
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  • 8
    In: International Journal of Hematology, Springer Science and Business Media LLC, Vol. 113, No. 1 ( 2021-01), p. 81-91
    Type of Medium: Online Resource
    ISSN: 0925-5710 , 1865-3774
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2028991-1
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  • 9
    In: Journal of Korean Medical Science, XMLink, Vol. 28, No. 1 ( 2013), p. 80-
    Type of Medium: Online Resource
    ISSN: 1011-8934 , 1598-6357
    Language: English
    Publisher: XMLink
    Publication Date: 2013
    detail.hit.zdb_id: 2056822-8
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  • 10
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5138-5138
    Abstract: Abstract 5138 Background: Response to treatment has been associated with improved survival in multiple myeloma (MM). The use of novel agents changed achievement of CR rates compared with conventional chemotherapy. The purpose of our study is to show influence of early response after treated with bortezomib combined chemotherapy to survival in patients with newly diagnosed MM who are ineligible for stem cell transplantation. Methods: We assessed response at least forth cycles before next chemotherapy by international myeloma working group response criteria. The median duration from starting chemotherapy to initial response date was 2.3 month (range; 0.9 – 3.7 months). The enrolled cases were all received bortezomib combined chemotherapy as front line therapy. We divided into good response group (A group) which were included showing more than very good partial response (VGPR) and poor response group (B group) which were partial response (PR) or less than PR. Endpoints were comparision of progression free survival (PFS) and overall survival (OS) between A and B groups. Results: We retrospectively analyzed 129 patients registered data for our study from the Korean Multiple Myeloma Working Party (KMMWP) performed a nationwide registration of MM patients. In our results of initial response, 16 patients were in CR (12.4%), 50 were in VGPR (38.8%), 40 were in PR (31.0%), 14 were in SD (10.9%), and 9 were in PD (7.0%). However, in results of best responses, 46 patients were in CR (35.7%), 31 were in VGPR (24.0%), 32 were in PR (24.8%), 11 were in SD (8.5%) and 9 were in PD (7.0%). 3 years PFS of A group and B group were 55.6% and 18.4%, respectively (p-value 〈 0.001). 3 years OS of A and B group were 65.3% and 52.9%, respectively (p-value 0.078). Conclusion: Early response at least forth cycles before next chemotherapy might be helpful for prediction of PFS in patients who were ineligible stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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    detail.hit.zdb_id: 80069-7
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