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  • 1
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4365-4365
    Abstract: Abstract 4365 Background Ovarian cancer is one of the most chemotherapy sensitive solid tumors. However, the role of dose intensity in the chemotherapy of advanced epithelial ovarian cancer has remained controversial. Accordingly, the current study attempted to analyze the outcome of high dose chemotherapy and autologous peripheral blood stem cell transplantation for ovarian cancer retrospectively. Methods Clinical data were collected retrospectively from 6 transplant centers in Korea between January 1996 and July 2008. Results Twenty three patients of total 6 centers were analyzed. The median age of the patients was 52 years (40-62 years). Nineteen patients (82.6%) were platinum sensitive and 4 patients were not. The conditioning regimens were reported to be ICE (ifosfamide, carboplatin, and etoposide) in 43.5 %, CTM (cyclophospamide, thiotepa, and melphalan) in 26.1 %, melphalan in 13%, other in 17.4 %. The median time to attain a neutrophil count greater than 500/mm3, following the transplantation, was 13 days (4∼38), and to attain a platelet count greater than 20,000/mm3, was 13 days (4∼38 days). There was primary graft failure of platelet in 3 patients. The median duration of progression free survival and overall survival were 6.3 months (95% CI, 0-19.3) and 19.7 months (95% CI, 10-29.4). The median overall survival was 25.9 months in the platinum sensitive patients and 17.4 months in the platinum resistant patients, however, there was no statistically significant difference in PFS between two groups. Poor prognostic factor for survival which retained statistical significance at multivariate level were platinum resistance (p=0.06, RR 3.99; 95% CI, 0.94-16.97) and clear cell type (p=0.015, RR 9.63; 95% CI, 1.56-59.45). Conclusion Some subgroups (non clear cell types, platinum sensitive groups) of patients with ovarian cancer seem to have good outcomes after high dose chemotherapy with autologous stem cell transplantation, although several biases may have affected these observations. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 2
    In: Acta Haematologica, S. Karger AG, Vol. 122, No. 4 ( 2009), p. 200-210
    Abstract: 〈 i 〉 Aim: 〈 /i 〉 The Korean Multiple Myeloma Working Party performed a nationwide registration of multiple myeloma patients via a web-based data bank system. 〈 i 〉 Methods: 〈 /i 〉 We retrospectively analyzed registered data from 3,209 patients since 1999. 〈 i 〉 Results: 〈 /i 〉 The median overall survival (OS) was 50.13 months (95% confidence interval: 46.20–54.06 months). Patients ≤40 years demonstrated a longer OS than patients 〉 65 years of age (median OS 71.13 vs. 36.73 months, p 〈 0.001). Patients who received novel agents at any time during their treatments showed a longer OS than patients who did not (median OS 42.23 vs. 55.50 months, p 〈 0.001). Response to treatment was associated with OS, with tandem autologous stem cell transplantation (SCT) producing longer OS than single autologous SCT. 〈 i 〉 Conclusions: 〈 /i 〉 We demonstrated associations between survival outcomes and treatment modalities as well as baseline disease characteristics in a registry of multiple myeloma patients using a web-based data analysis.
    Type of Medium: Online Resource
    ISSN: 0001-5792 , 1421-9662
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
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  • 3
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4881-4881
    Abstract: Abstract 4881 Introduction The Korean Multiple Myeloma Working Party (KMMWP) initiated a nationwide registration of myeloma patients via a web page designated the “Korean Myeloma Registry.” This registry includes demographic features, characteristics of disease, treatment outcomes, and survival status. Herein, we retrospectively reviewed data representing 3,209 Korean myeloma patients. Methods Members of the registry committee of the KMMWP designed the web-based registration site for the “Korean Myeloma Registry (www.myeloma.or.kr).” A total of 3,209 patients were registered from 39 hospitals. Each one of participated hospitals registered their patients who were diagnosed as MM between the years 1999 and 2009. The approximate duration of registration was from May 2005 until March 2009; following collection, the data was downloaded for analysis. Results The median age at diagnosis was 64 years (range, 20 – 93 years) with 84 patients ' 40 years of age; this included three patients 〈 30 years of age (ages 20, 28, and 29 years old). Poor performance status (ECOG grade 2-3), anemia (Hgb 〈 10 g/dL), hypoalbuminemia ( 〈 3.5 g/dL), and elevated serum β2 microglobulin ( 〉 5.5 mg/dL) were more frequently observed in the 〉 65 years of age group than in the groups '65 years of age. Thus, an advanced ISS stage was more common in patients older than 65 years. The most common idiotype of myeloma was IgG (46.0%, 1475/3209), followed by IgA type (18.6%). Non-secretory myeloma accounted for 4.4% of cases, with IgD, IgM, and IgE subtypes being very rare. However, patients ' 40 years of age demonstrated a tendency toward a higher incidence of the IgD type (7.1%, 6/84) and light chain disease (22.6%, 19/84) compared to the other age groups. Other characteristics, including the presence of extramedullary plasmacytoma, demonstrated a similar pattern among the groups. Chromosomal studies of bone marrow aspirates were performed in 1,943 patients with 499 patients (25.7%) demonstrating abnormalities. In 60.9% of patients (1,954/3,209), an objective response to induction treatment included complete response (CR), partial response (PR), and minimal response (MR) (Table 4); 463 patients demonstrated progressive disease (PD) during induction treatment. Response could not be evaluated in 300 patients (9.3%) due to early drop out, including follow-up loss and early death. Eight hundred four patients (25.1%) received SCT. The majority of patients (23.1%, 741 patients) received autologous SCT within one year of diagnosis; designated as “early transplantation.” Autologous SCT was performed in those patients who achieved an objective response following induction treatment. Sixty three patients (2.0%) underwent autologous SCT after relapse; designated as “delayed transplantation.” Five hundred eighty patients received single autologous SCT. Tandem autologous SCT was performed in 134 patients. Allogeneic SCT was performed for 63 patients following autologous SCT. The median OS was 50.13 months (95% confidence interval (CI) of 46.20 – 54.06 months). When OS was compared according to age strata, patients '40 years of age demonstrated a prolonged OS (median OS of 71.13 months) compared with patients 〉 65 years of age (median OS of 36.73 months, P 〈 0.001). When we compared the survival of patients who received novel agents such as bortezomib or thalidomide at any time during the course of their treatments with patients who did not receive novel agents, there was a significant difference of OS between two groups (median OS 42.23 versus 55.50 months, P 〈 0.001). Tandem autologous SCT produced a superior OS when compared with single autologous SCT. Furthermore, patients who underwent delayed SCT demonstrated a longer OS compared with early SCT (P = 0.017). Multivariate analysis found that age 〉 65 years, poor performance status, platelet count 〈 100,000/μL, serum albumin 〈 3.5 g/dL, serum creatinine ≥ 2.0 mg/dL, serum β2 microglobulin ≥ 3.5 mg/dL, the presence of extramedullary plasmacytoma, and the presence of chromosomal abnormalities were all found to be independent prognostic factors for OS. Conclusion In this study, we demonstrate improved survival of patients with multiple myeloma after the introduction of novel agents and autologous stem cell transplantation. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 4
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4902-4902
    Abstract: Abstract 4902 Introduction Cytogenetics and fluorescent-in situ hybridization (FISH) are important outcome predictors in multiple myeloma (MM). There were only few small studies that investigated prognostic implication of FISH and/or conventional karyotyping in Korean MM patients. We investigated the incidences and prognostic significances of chromosomal abnormalities detected by FISH and/or conventional karyotyping among Korean MM patients. Patients and Methods We collected data of patients from Korean Myeloma Registry and performed retrospective analysis. We compared the survival of patients with chromosomal abnormalities and other clinical findings. Results From 2000 to 2009, total of 801 newly diagnosed myeloma patients were enrolled in this study. Median age of patients was 62 years. Median overall survival was 82 months, and median follow up of time was 92 months. Among the patients who had conventional karyotype analysis, 17.1% were complex karyotype, followed by del13q (7.4%), hyperdiploidy (7.6%), hypodiploidy (3.0%), and t(11;14) (3.9%). Among the patients who had FISH analysis, 22.8% were del 13q, followed by t(11;14) (18.2%), t(4;14) (13.7%), del17p (11.8%) and t(14;16) (5.9%). Univariate analyses revealed that complex karyotype (p 〈 0.01), hypodiploidy (p=0.01), del13q (p 〈 0.01) by conventional karyotyping, and t(4;14) (p=0.04) by FISH negatively impacted the overall survival. Other genomic aberrations did not affect the overall survival. Clinical parameters that impact on overall survival were percentage of plasma cells in bone marrow, serum beta2-microglobulin, creatinine, low hemoglobin, and low albumin levels. On multivariate analysis, percentage of plasma cells in bone marrow (p 〈 0.01) and low serum albumin level (p 〈 0.01) were independent risk factors for overall survival. Conclusions Our results showed that complex karyotype, hypodiploidy, t(4;14), and del13q by FISH and/or conventional karyotyping were negative prognostic factors for overall survival in univariate analyses. On multivariate analysis, low serum albumin level and percentage of plasma cells in bone marrow were independent risk factors for overall survival. In future, prospective trial with laboratory standardization is warranted for more reliable results from FISH and/or conventional karyotyping in MM patients. Disclosures Suh: Janssen Korea: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 5
    Online Resource
    Online Resource
    Annals of Laboratory Medicine ; 2007
    In:  Annals of Laboratory Medicine Vol. 27, No. 3 ( 2007-06-01), p. 188-191
    In: Annals of Laboratory Medicine, Annals of Laboratory Medicine, Vol. 27, No. 3 ( 2007-06-01), p. 188-191
    Type of Medium: Online Resource
    ISSN: 2234-3806 , 2234-3814
    Language: English
    Publisher: Annals of Laboratory Medicine
    Publication Date: 2007
    detail.hit.zdb_id: 2677441-0
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2006
    In:  Surgery Today Vol. 36, No. 9 ( 2006-09-28), p. 831-834
    In: Surgery Today, Springer Science and Business Media LLC, Vol. 36, No. 9 ( 2006-09-28), p. 831-834
    Type of Medium: Online Resource
    ISSN: 0941-1291 , 1436-2813
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2006
    detail.hit.zdb_id: 1463169-6
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  • 7
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3221-3221
    Abstract: Introduction Imatinib mesylate (IMT) dose escalation has been proposed as a therapeutic option in patients (Pts) with chronic myeloid leukemia (CML) who failed to achieve optimal response with standard dose IMT. We report the results of prospective multi-center single arm phase ¥≥study evaluating efficacy of escalated dose IMT. We intended to identify patterns of molecular change using serial quantitative RT-PCR and its relationship with clinical outcome. We also planned to find predictive markers for outcome with array comparative genomic hybridization (aCGH) and epigenetic study of bcr gene in addition to BCR/ABL mutation. Patient and methods Pts in chronic phase (CP) CML who failed to achieve optimal response by European LeukemiaNET with adequate organ function were enrolled. Pts in accelerated phase (AP) or blast crisis (BC) who failed to achieve complete hematologic response after 3 months of IMT were also eligible. CP Pts received 600mg daily, while Pts in AP or BC received 600 or 800mg IMT daily. Pts received IMT for at least 12 months or until the appearance of a progressive disease, intolerable toxicity. Along with cytogenetic response (CyR), molecular response (MR) was assessed with BCR-ABL/ABL gene ratio of peripheral blood or bone marrow aspirate. Baseline BCR/ABL gene mutation test was performed using Matrix-assisted laser desorption/ionization time of flight mass spectrometry. Genome-wide screening for regions of genetic gains and losses with baseline blood samples was performed for 38 Pts using aCGH. Methylation status of 4 CpG sites in bcr gene promoter region was tested for 40 Pts and average methylation level was used for analysis. Blood samples at baseline and 6 months after dose escalation were tested. 29 optimal responders to standard dose IMT and 38 healthy donors were also tested for bcr methylation status for additional comparison. Results 71 Pts (median age 49.0 years, M:F=50:21) received escalated dose IMT. Median time to treatment failure (TTTFx) was 18.0 months and toxicities were manageable. 44 and 52 Pts were evaluable for FISH at 6 months and 1 year, where 16 and 17 Pts showed complete CyR (CCyR) respectively. For 61 Pts with serial MR data, TTTFx was longer in Pts who achieved molecular reduction of more than 50% within 6 months (Molecular early responder: MER) than who didn’t (p & lt;0.001). MER’s achieved CCyR more frequently at 6 months and 12 months (p=0.010, & lt;0.001 respectively). Of 24 Pts who had mutational status data, 4 had mutation. They experienced TFx within 12 months and all failed to achieve CCyR. aCGH revealed significant copy number (CN) gain in chromosome 16p11.2 in MER’s compared to non-MER’s (p=0.034). Tendency for increased CN in 22q11.23 and decreased CN in 17q12 was observed in MER’s without reaching statistical significance (p=0.072 and 0.070 respectively). 4 candidate genes within the above regions – GSTT1, SULTA1A, PYCARD, TADAZL – were evaluated for CN variation. GSTT1 CN loss was more frequently observed in MER’s (p=0.035). GSTT1 CN loss also predicted the longer TTTFx without reaching statistical significance (p=0.086). In epigenetic study, Pts in PCyR at the time of study enrollment had increased baseline bcr methylation compared to Pts in less than PCyR (p & lt;0.001). Pts who had increased amount of bcr methylation at 6 months compared to baseline had longer TTTFx compared to who did not (p=0.012). Baseline bcr methylation amount of study Pts was lower when compared to that of optimal responders and healthy donors (p=0.001 and p & lt;0.001 respectively). bcr methylation decreased with increased duration of standard dose IMT both in study Pts and optimal responders (p=0.042 and 0.004 respectively), although the pattern of decrease was different between the two groups (p & lt;0.001). In multivariate analysis baseline bcr methylation status was the only variable related to TTTFx (p=0.047). Conclusion Escalated dose IMT is a reasonable option for CML Pts showing less than optimal response to standard IMT. MER after escalated dose IMT is a useful early predictive marker for long term response. Mutational status of BCR-ABL at baseline is possibly important for response. Chromosome 16p11.2, 22q11.23 and 17q12 are potential locations related to IMT response and GSTT1 CN loss may be a genetic change affecting clinical outcome. bcr methylation status is an epigenetic marker associated with IMT response, where decreased bcr methylation status is related to poor IMT response.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 8
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1516-1516
    Abstract: Abstract 1516 Background: Front-line combination of imatinib with conventional chemotherapy has demonstrated an improved complete remission (CR) rate, an increased transplantation proceeding rate with CR, and a better survival in adults with Ph+ ALL. However, in the light of disease aggressiveness and recurrence, mainly as a result of the outgrowth of leukemic subclones with imatinib-resistant mutations, an improved strategy to induce more effective leukemic cell clearance is clearly needed. Dasatinib, a potent dual BCR-ABL/SRC family kinase inhibitor, has been shown to be effective in patients with imatinib-resistant chronic myeloid leukemia and Ph+ ALL. Methods: We present the first interim results of the Korean prospective phase II study protocol designed to evaluate the clinical efficacy of first-line dasatinib plus conventional chemotherapy for adults with newly diagnosed Ph+ ALL. This study is registered at www.ClinicalTrials.gov as NCT01004497. The protocol is designed for 51 patients, and recruitment started in March, 2010. The protocol enrolls patients (15–65 years) who receive dasatinib (100 mg once daily for 4 weeks) as an alternative schedule after each conventional chemotherapy course (alternating modified hyper-CVAD and high-dose cytarabine/mitoxantrone). Patients in CR who have a suitable related/unrelated donor undergo allogeneic transplantation as early as possible (depending on the speed of coordination process). Patients without a donor continue to receive dasatinib plus conventional chemotherapy (up to 4 courses; depending on the patient's tolerability) followed by dasatinib maintenance therapy (100 mg once daily for up to 2 years). Minimal residual disease monitoring for BCR-ABL transcript is centrally evaluated by real-time quantitative PCR (4.5 log sensitivity) through handling of bone marrow samples from all patients (Research Institute of Molecular Genetics, The Catholic University of Korea, Seoul, Korea). Results: A total of 36 patients have been enrolled to date. Of these, 3 patients are receiving the first dasatinib cycle (too early); 3 patients died before starting the first dasatinib cycle from infections. Thus, 30 patients are evaluable for assessment of response to dasatinib plus conventional chemotherapy. Median age was 47 years (range, 19 to 64 years). Karyotype analysis revealed additional chromosomal changes in 18 (60%) of the 30 patients. Twenty patients (67%) had m-BCR transcript. All patients (100%) have achieved CR with a decrease in the minimal residual disease by the first dasatinib cycle, and of these, 13 patients (43%) have achieved major molecular response [MMR; including 5 complete molecular response (CMR4.5)]. By the second dasatinib cycle, 25 patients (83%) have achieved MMR (including 11 CMR4.5). So far, no dasatinib-related serious adverse events (≥grade 3 toxicity) have been observed. Twenty-four (80%) of the 30 patients have undergone allogeneic transplantation in CR; 6 patients are receiving continuous dasatinib plus conventional chemotherapy in CR. With a median follow-up duration of 10 months (range, 5 to 17 months), 25 patients are at present alive in continuous CR, and 4 patients have died (2 infections during consolidation chemotherapy, 2 transplant-related complications). Only 1 patient who failed to achieve MMR has relapsed at 11 months from diagnosis (at 5 months after allogeneic transplantation). The estimated probabilities of disease-free survival and overall survival at 1 year were 76% and 83%, respectively. Conclusions: Our interim analysis indicates that first-line combination of dasatinib with conventional chemotherapy appears to be effective in achieving a good quality of molecular response (MMR/CMR4.5) in adults with Ph+ ALL. Whether this would translate to an improved long-term survival remains to be investigated. Disclosures: Lee: Bristol Myers Squibb: Honoraria, Research Funding. Kim:Bristol Myers Squibb: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 9
    Online Resource
    Online Resource
    Elsevier BV ; 2004
    In:  Journal of Systems Architecture Vol. 50, No. 4 ( 2004-3), p. 169-175
    In: Journal of Systems Architecture, Elsevier BV, Vol. 50, No. 4 ( 2004-3), p. 169-175
    Type of Medium: Online Resource
    ISSN: 1383-7621
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2004
    detail.hit.zdb_id: 1499743-5
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  • 10
    In: Journal of the American Academy of Dermatology, Elsevier BV, Vol. 84, No. 6 ( 2021-06), p. 1619-1627
    Type of Medium: Online Resource
    ISSN: 0190-9622
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2001404-1
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