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  • 1
    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
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  • 2
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 9498-9500
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
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  • 3
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4871-4871
    Abstract: Abstract 4871 BACKGROUND Bortezomib is increasingly being employed as an important treatment for relapsed/refractory patients with multiple myeloma (MM) who have received at least one prior therapy. Osteolytic bone disease is a major problem in the management of MM. Myeloma bone disease is a result of excessive osteoclast activation and impaired osteoblast function. METHODS This study aimed to evaluate the effect of bortezomib on bone remodeling in the patients with MM who received one prior therapy. Total 104 patients were enrolled and serum samples were collected from 81 patients at baseline and after 4 cycles of bortezomib treatment, respectively. An enzyme linked immunosorbent assay (ELISA) was used for the detection of the following serum markers; (1) the osteoblastic markers including serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), (2) dickkopf-1 (DKK-1), an osteoblastic inhibitor and (3) a main inducer of osteoclast activity, receptor activator nuclear factor κB ligand (RANKL) and its soluble decoy receptor, osteoprotegerin (OPG). RESULTS There was no correlation between bone disease status and the concentrations of the bone markers; patients with myeloma bone disease at baseline did not have increased values of DKK-1, RANKL and RANKL/OPG ratio as well as decreased levels of OC and BAP when compared with those without osteolytic bone lesions. To our surprise, there was also a strong tendency towards a negative correlation with serum levels of OC (P=.009) and BAP (P=.049) and disease duration (≥ vs. 〈 6 months). Moreover, DKK-1 concentrations were positively associated with disease duration (P=.047). The objective response rate (≥ partial response) after four cycles of therapy was 58%. Bortezomib administration significantly reduced serum DKK-1 (P=.011) and sRANKL/OPG ratio (P=.034) after 4 cycles irrespective of treatment response. OPG levels were significantly different according to the type of previous therapy (stem cell transplantation vs. alkylator-based, P=.029) CONCLUSIONS This study suggests that bortezomib can inhibit the down-regulation of osteoblastic response and bone resorption by reducing circulating levels of DKK-1 and sRANKL/OPG ratio. Serum concentrations of the bone-remodeling markers can be different according to the disease duration rather than the status of bone disease. Bortezomib treatment early after diagnosis may benefit myeloma patients with bone disease considering that the change of bone markers was bound up with disease duration. Disclosures Min: Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Lee:Janssen Korea: Research Funding. Suh:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Yoon:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Kang:Janssen Korea: Research Funding. Choi:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Kwak:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Joo:Janssen Korea: Research Funding. Mun:Janssen Korea: Research Funding. Jo:Janssen Korea: Research Funding. Park:Janssen Korea: Research Funding. Park:Janssen Korea: Research Funding. Kim:Janssen Korea: 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: 2009
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  • 4
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2844-2844
    Abstract: Introduction Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of diseases associated with poor prognosis, representing 10-15% of non-Hodgkin lymphomas. Although CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens are often preferred as 1st line treatment, the treatment outcome is poor with 5-year overall survival (OS) rate of 30-40%. In an effort to improve the survival outcomes of these patients, autologous hematopoietic stem cell transplantation (ASCT) as an upfront consolidative treatment has been proposed for patients achieving partial or complete remission after induction therapy. However, the role of ASCT still remains undefined since no randomized trials have demonstrated survival benefit of ASCT in this setting. To better understand the clinical characteristics, treatment patterns, and outcomes in patients with PTCL, we have conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with PTCL. Methods Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored (ClinicalTrials.gov, no. NCT02364466). All patients were pathologically diagnosed with PTCL according to the 2008 World Health Organization classification of lymphoid neoplasms. Extranodal NK/T cell lymphoma, cutaneous T cell lymphoma, Mycosis fungoides and Sezary syndrome were excluded. The target number for enrollment was 200, and an interim analysis was previously reported at the time of enrollment of 155 patients (ASH 2017). An updated analysis of 198 patients was performed. Results The median age was 59 years (range, 49-70), 122 patients (61.6%) were male and 168 (84.9%) had ECOG performance status of 0-1. PTCL, not otherwise specified was the most common pathologic subtype (n = 80, 40.4%), followed by angioimmunoblastic T cell lymphoma (n = 60, 30.3%). The most frequently administered 1st line regimen was CHOP or CHOP-like regimen (n = 165, 83.3%), followed by ICE (ifosfamide, carboplatin, and etoposide) or ICE-like regimen (n = 23, 11.6%), and others (n = 10, 5.1%). With a median follow-up duration of 28.2 months (95% CI, 25.6-30.6), 2-yr progression-free survival (PFS) rate was 44.4% (95% CI, 37.5-57.4) and 2-yr OS rate was 64.4% (95% CI, 57.4-72.1). Response evaluation for 1st line regimens were available in 175 patients. Among these patients, there was no significant difference in overall response rate (ORR) and complete response (CR) rate between patients treated with CHOP or CHOP-like vs. ICE or ICE-like regimen (ORR: 73.6 vs. 72.7%, P = 1.000; CR rate: 58.1% vs. 45.5%, P = 0.375). In addition, no significant difference was observed regarding PFS and OS between the two treatment groups (CHOP or CHOP-like vs. ICE or ICE-like; 2-yr PFS rate: 45.2 vs. 38.3%, P = 0.39; 2-year OS rate: 65.7 vs. 50.7% P = 0.43) (Figure 1A, B). Among 121 patients younger than 65 years of age who are eligible for transplantation, autologous hematopoietic stem cell transplantation (ASCT) was performed as an upfront consolidative treatment in 51 patients (42.1%). Patients who received upfront ASCT was associated with significantly better PFS and OS compared with patients who did not, with a 2-yr PFS rate of 52.3 vs. 37.0% (P = 0.032) and 2-yr OS rate of 74.2 vs. 57.1% (P = 0.028), respectively (Figure 2A, B). A total of 81 patients were treated with 2nd line chemotherapy for refractory or relapsed disease, and response evaluation for 2nd line chemotherapy was available in 63 patients. Among these patients ORR and CR rate were 49.2% and 30.2%, respectively. Conclusion Our study demonstrated that survival outcome with current treatment options for patients with PTCL remains poor. Although CHOP or CHOP-like regimens were the most commonly used 1st line regimens, no survival benefit was observed when compared with ICE or ICE-like regimens, suggesting that more efforts are needed to establish a standard 1st line treatment for PTCL. ASCT may provide survival benefit in transplant eligible patients, which warrants further evaluation in randomized controlled trials. Disclosures Yoon: Janssen: Consultancy; MSD: Consultancy; Novartis: Consultancy, Honoraria; Yuhan Pharma: Research Funding; Amgen: Consultancy, Honoraria; Genentech, Inc.: Research Funding; Kyowa Hako Kirin: Research Funding. Kim:F. Hoffmann-La Roche Ltd: Research Funding; Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: 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: 2019
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  • 5
    In: American Journal of Gastroenterology, Ovid Technologies (Wolters Kluwer Health), Vol. 118, No. 8 ( 2023-08), p. 1373-1380
    Abstract: This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. METHODS: We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to 〉 10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline. RESULTS: No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37–214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37–183 days). DISCUSSION: Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF (ClinicalTrials.gov ID: NCT02354846).
    Type of Medium: Online Resource
    ISSN: 0002-9270 , 1572-0241
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 6
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2683-2683
    Abstract: Abstract 2683 Background Secondary central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) includes CNS relapse or CNS involvement with systemic disease progression. Although many publications have provided information regarding the incidence and risk factors for CNS involvement in DLBCL, its incidence reported across those studies varies widely. It might be related with that the majority of data were from retrospective analyses. Furthermore, the role of CNS prophylaxis for DLBCL has been challenged, especially in the era of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). As a result, this rare but fatal clinical problem still remains a therapeutic dilemma in the management of DLBCL. In this study, we prospectively explored the risk factors of CNS involvement and the clinical impact of screening evaluation for CNS involvement. Methods We analyzed the incidence of secondary CNS involvement in pathologically confirmed DLBCL patients enrolled in the Prospective Cohort Study with Risk-adapted Central Nervous System Evaluation in Diffuse Large B-cell Lymphoma (PROCESS study, NCT01202448). Patients should be treated with at least one cycle of R-CHOP, and provide written informed consents. We assessed the risk of CNS involvement based on previously reported risk factors: serum LDH elevation, the number of extranodal involvements, serum albumin, bone marrow invasion, HIV positivity, the involvement of testis, breast, paranasal sinus, bone, retroperitoneal lymph nodes, orbit, and epidural space. If patients had any of these risk factors, they underwent CSF study to screen the CNS involvement at diagnosis. If the results were abnormal, additional studies including brain MRI could be done depending on physicians' decision. CNS prophylaxis was done with intrathecal chemotherapy with methotrexate for patients who had positive findings of screening evaluation or were determined to have a risk of CNS involvement based on physicians' decision. Results 564 patients were enrolled between 2010 and 2012 from 26 institutions belonged to the Consortium for Improving Survival of Lymphoma (CISL). They were prospectively monitored with the median follow-up duration of 10.5 months. The median age was 59.5 years old (range 20–89 years), and approximately a half of patients had Ann Arbor stage III/IV (n = 276, 48.9%) and 193 patients involved two or more than two extranodal sites (34.2%). Based on the International Prognostic Index (IPI) risk, 192 patients belonged to high or high-intermediate risk (34%). Among patients (n = 368) who had at least one of risk factors for CNS involvement, 243 patients underwent CNS evaluation, and the evidence of CNS involvement was found in16 patients including positive cytology (n = 11), and brain parenchyma lesion (n = 5). The other 78 patients showed equivocal results of CSF analysis including the presence of atypical cells (n = 17). Intrathecal prophylaxis was done for 51 patients whereas high dose methotrexate chemotherapy was combined with R-CHOP for patients with brain lesion. During follow-up, 14 cases of additional CNS involvement including brain parenchyma (n = 8), leptomeningeal (n = 5), and ocular invasion (n = 1) were observed. The median time to CNS event in these 14 patients was 7.5 months (range 1.2 – 15.9 months). Thus, 30 cases of secondary CNS involvement were documented in our study population at the time of analysis (5.3%) including 16 cases at diagnosis and 14 cases during follow-up. The univariate analysis for evaluation of risk factors demonstrated serum LDH, the number of extranodal involvements, bone marrow invasion, and the involvement of retroperitoneal lymph nodes, breast, paranasal sinus and orbit were significantly associated with CNS involvement. The high/high-intermediate risk of IPI was also predictive of CNS involvement (P 〈 0.05). However, in the multivariate analysis, bone marrow invasion and the involvement of breast, paranasal sinus and orbit were independently predictive for CNS involvement. Conclusions The incidence of secondary CNS involvement in DLBCL patients treated with R-CHOP was around 5%, and a half of cases had the evidence of CNS involvement at diagnosis. Considering a particular risk of CNS involvement of disease-related factors, risk-adapted active screening against CNS involvement may help to improve treatment outcome of patients with DLBCL. 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: 2012
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  • 7
    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
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 8
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4421-4421
    Abstract: Introduction Although several previous studies addressed the role of radiation in treating localized diffuse large B-cell lymphoma (DLBCL), chemotherapy alone has shown promising efficacy with the emergence of Rituximab. Thus, we evaluated the clinical efficacy outcomes and failure patterns of patients with localized DLBCL according to two different treatment strategies, either 6 or more cycles of R-CHOP chemotherapy alone or 3 or 4 cycles of R-CHOP followed by involved field radiotherapy (IFRT). Methods A prospectively collected database from 21 tertiary centers participating the Consortium for Improving Survival of Lymphoma (CISL), built up for PROCESS study (NCT01202448) for secondary central nervous system involvement in DLBCL, was recruited for current study in addition to the Asan Medical Center (AMC) Lymphoma Registry. CISL database and AMC lymphoma registry consisted of data from patients with newly diagnosed DLBCL between August 2010 and August 2012, and between February 2004 and February 2012, respectively. Inclusion criteria were localized (stage I or II), non-bulky ( 〈 10cm in longest diameter) DLBCL treated with R-CHOP as 1st line chemotherapy, and patients either who received 6 or more cycles of R-CHOP chemotherapy only (R-CHOP alone group) or received 3 or 4 cycles of R-CHOP chemotherapy followed by IFRT (R-CHOP plus RT group). Comparisons of clinicopathologic parameters, clinical outcomes and the patterns of relapse were performed between two groups. The types of relapse were classified as either locoregional or distant, according to whether it involves any separate region from primary sites. Efficacy outcomes included complete response (CR) rate, 2-year overall survival (OS) rate, and 2-year event-free survival (EFS) rate. Results A total of 357 patients (CISL prospective cohort: 161 patients, AMC registry: 196 patients) were eligible for the analyses. Two hundred ninety nine patients (83.5%) received 6 or more cycles of R-CHOP chemotherapy alone, and 58 patients (16.2%) underwent 3 or 4 cycles of R-CHOP followed by IFRT. Median age was 54 years (range, 16-87). During the median follow-up of 24 months (range, 4-116 months), 35 patients (9.8%) experienced relapse, and 22 patients (6.1%) died. Two-year OS and EFS rate was 94.7% and 89.9%, respectively, and 345 out of 357 patients (96.6%) achieved CR. Comparing R-CHOP alone to R-CHOP plus RT group, there was no significant difference in clinicopathologic parameters. R-CHOP alone could achieve significantly higher CR rate of 97.7 % than 91.4% of R-CHOP plus RT group (p = 0.030). Two-year OS and EFS were significantly longer in R-CHOP alone group than R-CHOP plus RT group (96.1 vs 89.9 %, p = 0.029 and 91.7% vs 81.8%, p= 0.028) (Figure 1). Relapse rate was significantly lower in R-CHOP alone group compared with R-CHOP plus RT group than group (7.4% vs 22.4%, p=0.001), and distant relapses were also significantly lower (15.5% vs 2.7%, p 〈 0.001). In addition, even only in relapsed patients, R-CHOP alone group showed lower incidence of distant relapses with marginal statistical significance (36.4% vs 69.2 %, p=0.062) (Table 1). Conclusion In our cohort, R-CHOP alone for six to eight cycles without IFRT could achieve significantly higher 2-year OS and EFS rate as well as CR compared with R-CHOP plus RT group. In addition, the rate of relapse and systemic failure were significantly lower in R-CHOP alone group, which altogether warrant further validation in prospective trial. Table 1. Explorative comparison of overall clinical outcomes and patterns of relapse between two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Total (%) R-CHOP alone group (%) R-CHOP plus RT group (%) P -value Number of patients 357 (100) 299 (83.5) 58 (16.2) Treatment response Complete response 345 (96.6) 292 (97.7) 53 (91.4) 0.030 Overall response 351 (98.3) 294 (98.3) 57 (98.3) 1.000 Rate of relapse 35 (9.8%) 14 (7.4) 11 (22.4) 〈 0.001 Median time to relapse (95% CI) 11 (7-15) 11 (8-14) 10 (5-14) 0.346 Pattern of relapse 〈 0.001 (0.062) Locoregional 14 (4.7) (63.6) 4 (6.9) (30.8) Distant 8 (2.7) (36.4) 9 (15.5) (69.2) Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 2 Figure 2. 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: 2014
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 27, No. 35 ( 2009-12-10), p. 6027-6032
    Abstract: On the basis of the benefits of frontline radiation in early-stage, extranodal, natural killer (NK)/T-cell lymphoma (ENKTL), we conducted a phase II trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of etoposide, ifosfamide, cisplatin, and dexamethasone (VIPD). Patients and Methods Thirty patients with newly diagnosed, stages IE to IIE, nasal ENKTL received CCRT (ie radiation 40 to 52.8 Gy and cisplatin 30 mg/m 2 weekly). Three cycles of VIPD (etoposide 100 mg/m 2 days 1 through 3, ifosfamide 1,200 mg/m 2 days 1 through 3, cisplatin 33 mg/m 2 days 1 through 3, and dexamethasone 40 mg days 1 through 4) were scheduled after CCRT. Results All patients completed CCRT, which resulted in 100% response that included 22 complete responses (CRs) and eight partial responses (PRs). The CR rate after CCRT was 73.3% (ie, 22 of 30 responses; 95% CI, 57.46 to 89.13). Twenty-six of 30 patients completed the planned three cycles of VIPD, whereas four patients did not because they withdrew (n = 2) or because they had an infection (n = 2). The overall response rate and the CR rate were 83.3% (ie; 25 of 30 responses; 95% CI, 65.28 to 94.36) and 80.0% (ie, 24 of 30 responses; 95% CI, 65.69 to 94.31), respectively. Only one patient experienced grade 3 toxicity during CCRT (nausea), whereas 12 of 29 patients experienced grade 4 neutropenia. The estimated 3-year, progression-free and overall survival rates were 85.19% (95% CI, 72.48 to 97.90) and 86.28% (95% CI, 73.97 to 98.59), respectively. Conclusion Patients with newly diagnosed, stages IE to IIE, nasal ENKTL are best treated with frontline CCRT.
    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: 2009
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  • 10
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4076-4076
    Abstract: Background: Primary breast diffuse large B-cell lymphoma (DLBCL) has poor outcomes with frequent extranodal failures, particularly in the central nervous system (CNS). To prevent CNS recurrence, we designed this phase II trial that addressed feasibility and activity of conventional immunochemotherapy and CNS prophylaxis. Methods: This prospective, multicenter, single-arm phase II study was conducted to evaluate efficacy and safety of 6 cycles of conventional rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP) with the addition of 4 doses of intrathecal methotrexate (IT MTX; 12mg) during the first 4 cycles of R-CHOP in patients with primary breast DLBCL. Primary breast lymphoma was defined as lymphoma involving one or both breasts as a sole extranodal site regardless of specific nodal involvement status. The primary end-point was 2-year progression-free survival (PFS). Secondary end-points included cumulative incidence of CNS recurrence, overall survival (OS), and safety. All patients provided written informed consents and the study was registered at www.clinicaltrials.gov as #NCT01448096. Results: Thirty-three patients with primary breast DLBCL were enrolled between Jan 2012 and Jul 2017 in the Consortium for Improving Survival of Lymphoma (CISL) member institutions. The median age was 50 years at diagnosis (range, 29-75) and all were female. Right breast involvement was more common than left (18 [55%] vs 14 [42%] ) and bilateral breast involvement was found in one patient (3%). Nodal involvement was present in 16 patients (49%), primarily in regional nodes (14 patients). Thus, the Ann Arbor stage was IE in 17 (52%), IIE in 13 (39%), IIIE in 2 (6.1%), and IV in 1 (3.0%). ECOG performance status was ≥2 in 1 patient (3%) and serum LDH level was elevated in 9 (27%). Therefore, the IPI and the CNS-IPI risk were mainly low (28 patients, 85%; respectively). No patients had CNS involvement at diagnosis. 32 (97%) of the 33 patients completed R-CHOP as planned, and the remaining patient withdraw a consent after four cycles of R-CHOP because of poor tolerance. CNS prophylaxis using IT MTX was completed as planned in 31 patients (94%), but it was discontinued in 2 patients because of patient's refusal. These 2 patients received two and three IT MTX doses, respectively. 32 patients (97%) were evaluable for treatment response and all these patients achieved a complete response. At the cutoff date of this analysis (10 Jul 2019), all patients who entered a follow-up phase had at least 24.0 months of follow-up. With a median follow-up duration of 46.1 months (IQR 31.1-66.8), 6 patients had experienced treatment failure and 3 of these died. The 2-year PFS and OS were 81.3% (95% CI, 67.7-94.8) and 93.5% (95% CI, 84.9-100.0), respectively (fig 1A and B). Of the 6 patients with treatment failure, diseases involved CNS with or without lymph nodes in 4 patients and breasts in 2 patients (1 ipsilateral and 1 contralateral breast recurrence). 3 of the four patients with CNS recurrence had isolated CNS recurrences (2 brain parenchymal and 1 meningeal disease) and one had a concurrent meningeal and lymph nodal recurrence. All 4 patients with CNS recurrence had received prophylactic IT MTX as planned by protocol. The 2-year cumulative incidence of CNS recurrence, taking into account the competing risk of death, was 12.5% (95% CI, 0.3-23.2, fig 1C). Although the number of patients with intermediate CNS-IPI risk was small (5 patients, 15%), the cumulative incidence of CNS recurrence did not differ significantly according to the CNS-IPI risk group. All CNS recurrences occurred within the first 2 years after enrolment. Toxicities were generally manageable during the R-CHOP and IT MTX treatment. No deaths as a result of toxicity occurred during treatment. Conclusion: Our study shows that conventional R-CHOP with prophylactic IT MTX is feasible in patients with primary breast DLBCL. However, given a substantially high rate of CNS recurrence, further studies to properly define the best strategy for CNS prophylaxis should be needed in patients with primary breast DLBCL. Figure 1 Disclosures Yoon: F. Hoffmann-La Roche Ltd: Research Funding. Kim:Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding; F. Hoffmann-La Roche Ltd: 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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