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  • 1
    In: Oncology Reports, Spandidos Publications, ( 2005-08-01)
    Type of Medium: Online Resource
    ISSN: 1021-335X , 1791-2431
    Language: Unknown
    Publisher: Spandidos Publications
    Publication Date: 2005
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  • 2
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2535-2535
    Abstract: Introduction: We conducted a randomized trial comparing two different doses of daunorubicin as induction chemotherapy in young adults with acute myeloid leukemia (AML) and showed intensification of induction therapy using a high daily dose of daunorubicin (90 mg/m2/d x 3d) improved both complete remission (CR) rate and survival duration compared to standard daunorubicin dose (45 mg/m2/d x 3d) (Lee JH et al. Blood 2011;118:3832). As it is necessary to compare the effects of high-dose daunorubicin with that of other agents, especially idarubicin, we performed another randomized trial comparing two induction regimens in young adults with AML: idarubicin vs. high-dose daunorubicin (ClinicalTrials.gov #NCT01145846). Here, we present final results of the study. Methods: Between May 2010 and March 2014, a total of 316 patients (65 years or younger) with newly diagnosed AML except acute promyelocytic leukemia were registered in this study. Seventeen patients were removed from the study (change of diagnosis in 11, patient's refusal to be randomized in 3 and other in 3) and the remaining 299 patients were analyzed. After random assignments, 149 patients received idarubicin (AI, 12 mg/m2/d x 3d) and 150 patients received high-dose daunorubicin (AD, 90 mg/m2/d x 3d) in addition to cytarabine (200 mg/m2/d x 7d) for induction of CR. Patients with persistent leukemia received the second attempt of induction chemotherapy, consisting of idarubicin (AI, 12 mg/m2/d x 2d) or daunorubicin (AD, 45 mg/m2/d x 2d) plus cytarabine (5d). Patients who attained CR received 4 cycles of high-dose cytarabine (3 g/m2 x 6 doses) in patients with good- or intermediate-risk cytogenetics and 4 cycles of cytarabine (1 g/m2 x 6d) plus etoposide (150 mg/m2 x 3d) in those with high-risk cytogenetics. Hematopoietic cell transplantation (HCT) was performed according to attending physician's discretion after one or two cycles of consolidation chemotherapy in most transplant cases. Results: CR was induced in 232 (77.6%) of 299 patients. Reasons for induction failure were resistant disease in 50, hypoplastic death in 5, and indeterminate cause in 12. As postremission therapy, 3 patients received no further treatment, 71 received consolidation chemotherapy without HCT, 137 underwent allogeneic HCT, and 21 underwent autologous HCT. The CR rates were not significantly different between two arms: 80.5% (120 of 149, AI) vs. 74.7% (112 of 150, AD) (P=0.224). With a median follow-up of 1046 days, overall survival probabilities at 4 years were 51.1% in AI vs. 54.7% in AD (P=0.756). The probabilities at 4 years for relapse-free survival were 63.5% in AI vs. 74.2% in AD (P=0.181) and those for event-free survival were 44.8% in AI vs. 50.7% in AD (P=0.738). Toxicity profiles were similar between two arms. Interestingly, overall and event-free survivals of 44 patients with FLT-ITD mutants (27 in AI and 17 in AD) were significantly different according to the induction regimens (AI vs AD; overall survival, 30.8% vs. 61.9%, P=0.030; event-free survival, 31.4% vs. 61.9%, P=0.025). Conclusions: The results of this phase 3 trial, which compared idarubicin (12 mg/m2/d x 3d) with high-dose daunorubicin (90 mg/m2/d x 3d), did not show significant differences between two arms in the outcomes of patients in terms of CR rates and overall, relapse-free or event-free survivals. In subset analysis, high-dose daunorubicin seems to be more effective than idarubicin in patients with FLT-ITD mutants. Disclosures Kim: Celgene: Research Funding; Alexion Pharmaceuticals: Research Funding; Il-Yang: Research Funding; Novartis: 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: 2015
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 24 ( 2017-08-20), p. 2754-2763
    Abstract: We compared two induction regimens, idarubicin (12 mg/m 2 /d for 3 days) versus high-dose daunorubicin (90 mg/m 2 /d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD] ) were analyzed. All patients received cytarabine (200 mg/m 2 /d for 7 days). Results Complete remission (CR) was induced in 232 patients (77.6%), with no difference in CR rates between the AI and AD arms (80.5% v 74.7%, respectively; P = .224). At a median follow-up time of 34.9 months, survival and relapse rates did not differ between the AI and AD arms (4-year overall survival, 51.1% v 54.7%, respectively; P = .756; cumulative incidence of relapse, 35.2% v 25.1%, respectively; P = .194; event-free survival, 45.5% v 50.8%, respectively; P = .772). Toxicity profiles were also similar in the two arms. Interestingly, overall and event-free survival times of patients with FLT3 internal tandem duplication (ITD) mutation were significantly different (AI v AD: median overall survival, 15.5 months v not reached, respectively; P = .030; event-free survival, 11.9 months v not reached, respectively; P = .028). Conclusion This phase III trial comparing idarubicin with high-dose daunorubicin did not find significant differences in CR rates, relapse, and survival. Significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 23 ( 2023-09), p. S189-S190
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 5
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1833-1833
    Abstract: The effectiveness of anthracycline dose intensification for induction of CR in AML has not been studied in a randomized fashion. We conducted a prospective randomized trial to compare the therapeutic efficacy and toxicity of two different doses of daunorubicin in combination with cytarabine in AML. This study began on August 2001 and 293 adult patients (younger than 60 years) with newly diagnosed AML except M3 have been enrolled. Fourteen patients were removed from the study and the remaining 279 patients were analyzed. After random assignments, 135 patients received standard-dose daunorubicin (SD-DN, 45 mg/m2/d × 3 d) and 144 patients received high-dose daunorubicin (HD-DN, 90 mg/m2/d × 3 d) in addition to cytarabine (200 mg/m2/d × 7 d) for induction of CR. Patients with persistent leukemia received the second attempt of induction chemotherapy, consisting of standard-dose daunorubicin (2 d) plus cytarabine (5 d). Patients who attained CR received 4 cycles of high-dose cytarabine (3 g/m2 × 6 doses) and 2 cycles of daunorubicin (1 d) plus cytarabine (5 d). For patients in intermediate- or high-risk cytogenetic groups, allogeneic hematopoietic cell transplantation was performed if there was a suitable donor. CR was induced in 98 of 135 patients (72.6%) in SD-DN arm and 119 of 144 (82.6%) in HD-DN arm (P = 0.044). The impact of daunorubicin dose intensification on the CR rates were different by cytogenetic risk group: the CR rates for SD-DN vs. HD-DN arm were 24/25 (96.0%) vs. 35/36 (97.2%) for good-risk group, 63/88 (71.6%) vs. 64/83 (77.1%) for intermediate-risk group, and 10/20 (50.0%) vs. 19/24 (79.2%) for poor-risk group. With a median follow-up of 596 days for surviving patients, the 4-year probabilities of overall survival, disease-free survival, and relapse-free survival were similar between SD-DN and HD-DN arm. Two different doses of daunorubicin (SD-DN vs. HD-DN) showed similar toxicity profiles regarding recovery times from myelosuppression, transfusion requirements, severe toxicities (grades III to IV) classified by NCI-CTC ver 2.0 including cardiac toxicities, and duration of antibiotics administration. In conclusion, high-dose daunorubicin showed higher CR rates in AML patients of intermediate- and poor- cytogenetic risk groups without increase of toxicities compared to standard-dose daunorubicin.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 6
    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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    detail.hit.zdb_id: 80008-9
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  • 7
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1707-1707
    Abstract: Abstract 1707 Core binding factor AML including t(8;21) and inv(16) have been associated with a relatively favorable prognosis compared with patients with normal or adverse karyotypes, and treated similarly. However, both t(8;21) and inv(16) AML seem to differ with respect to several biologic features and several reports demonstrated inferior outcome of t(8;21) compared with inv(16). Advanced age, higher WBC or granulocytic count, as well as CD56 expression or granulocytic sarcoma have been reported as poor prognostic factors in t(8;21) patients. Higher bone marrow (BM) blasts, lower platelets, and non-white race in t(8;21) AML adversely affected the probability to achieve CR. The KIT mutation is associated with poor prognosis in AML1-ETO-positive AML. Five-year survival rate was only around 40% in patients with t(8;21) having poor prognostic factors. Several chemotherapeutic strategies have been reported, among which high-dose cytarabine (HDAC) is generally the most effective option for successful postremission therapy. Furthermore, none of the randomized studies disclosed an advantage of allogeneic SCT (alloSCT) in this group of patients, given the relatively high treatment-related death (TRD) rate. Patients with t(8;21) AML with unfavorable prognosis may benefit from intensive postremission therapy such as early hematopoietic SCT. We conducted a retrospective study to investigate whether postremission therapies impact on survival according to prognostic factors in 132 AML patients with t(8;21) achieving first CR. Univariate analyses of prognostic factors for survival were performed in the patients with t(8;21), as well as more limited population of chemotherapy (CTx) group according to postremission therapies. The BM cellularity was a single most important independent prognostic factor on survival when using BM cellularity cutoffs as 90%. The 5-year overall survival (OS) in patients with t(8;21) and CTx group were significantly lower at 49.7% and 44.3% in patients with ≥ 90% BM cellularity, compared with 81.4% and 81.9% in those with 〈 90% BM cellularity, respectively (P = 0.001 and 0.027, respectively). The only other prognostic factor that influenced OS in CTx group was WBC count with cutoffs as 9.1 × 109/L. High WBC count was trend towards poor OS in CTx group (P = 0.067). In multivariate analysis, BM cellularity appeared to be the only independent prognostic factor for OS in either AML patients with t(8;21) (P = 0.002) or CTx group (P = 0.055). Interestingly, we found positive correlation between BM cellularity and WBC count (P = 0.013), peripheral blood (PB) blast percentage (P = 0.001) and serum LDH level (P = 0.017) but not hemoglobin level and BM blast percentage in a linear regression model. And also, we confirmed negative correlation between BM cellularity and platelet count (P = 0.009). It is speculated that BM cellularity represents on poor prognostic factors including WBC and platelet counts, and PB blast percentage in patients with t(8;21). By combining dichotomized WBC count and BM cellularity in a univariate analysis for OS in CTx group, three risk groups could be established: low risk group, WBC count less than 9.1 × 109/L and BM cellularity less than 90%; intermediate risk group, WBC count ≥ 9.1 × 109/L and BM cellularity less than 90%; high risk group, BM cellularity ≥ 90%. In CTx group, 5-year OS was 81.9% in low risk group, 64.8% in intermediate group, and 32.1% in high risk group (P = 0.041). In alloSCT group, 5-year OS was 94.1% in low risk group, 29.1% in intermediate risk group, and 77.8% in high risk group (P = 0.042). In low risk group, 5-year OS was 81.9% in CTx group, 65.6% in autologous SCT (autoSCT) group, 94.1% in alloSCT group. In intermediate risk group, 5-year OS was 64.8% in CTx group, 29.1% in alloSCT group. In high risk group, 5-year OS was 32.1% in CTx group, 52.5% in autoSCT group, and 77.8% in alloSCT group. We found that BM cellularity was the most powerful independent prognostic factor in AML patients with t(8;21). The newly proposed model using BM cellularity and WBC count demonstrated a simple and valid measurement as main prognostic factor. We suggest a risk-adapted postremissin strategies based on this prognostic model for AML with t(8;21) such as low and intermediate risk patients receiving three cycles or more than three cycles of HDAC CTx and high risk patients undergoing SCT in first CR as postremission therapy. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 8
    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
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    Online Resource
    Online Resource
    Korean Association of Internal Medicine ; 2021
    In:  The Korean Journal of Internal Medicine Vol. 36, No. 3 ( 2021-05-01), p. 491-514
    In: The Korean Journal of Internal Medicine, Korean Association of Internal Medicine, Vol. 36, No. 3 ( 2021-05-01), p. 491-514
    Type of Medium: Online Resource
    ISSN: 1226-3303 , 2005-6648
    Language: English
    Publisher: Korean Association of Internal Medicine
    Publication Date: 2021
    detail.hit.zdb_id: 2500508-X
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  • 10
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 7 ( 2020-07-21), p. 2310-
    Abstract: Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host disease (GVHD) prophylaxis regimens on clinical outcomes. From 16 centers in Korea, 41 acute myeloid leukemia (AML) and 29 ALL (acute lymphoblastic leukemia) patients undergoing CBT were enrolled. For AML patients, the neutrophil engraftment was observed in 87.5% of reduced intensity conditioning (RIC) and 72.0% of myeloablative conditioning (MAC) (p = 0.242). The median RFS was 5 months and OS 7 months. Conditioning regimen did not affect relapse free survival (RFS) or overall survival (OS). GVHD prophylaxis using calcineurin inhibitors (CNI) plus methotrexate was associated with better RFS compared to CNI plus ATG (p = 0.032). For ALL patients, neutrophil engraftment was observed in 55.6% of RIC and 90.0% of MAC (p = 0.034). The median RFS was 5 months and OS 19 months. MAC regimens, especially total body irradiation (TBI)-based regimen, were associated with both longer RFS and OS compared to other conditioning regimens. In conclusion, individualized conditioning regimens will add value in terms of enhancing safety and efficacy of CBT.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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