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  • American Society of Hematology  (12)
  • 1
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4725-4725
    Abstract: Background: In recent years, diffuse large B-cell lymphoma (DLBCL) has been classified into the germinal center B-cell (GC) type, the activated B-cell (ABC) type, and the type 3 using global gene expression profiling or immunohistochemical staining. It has been reported that the GC type DLBCL showed significantly longer survival than the non-GC (ABC and the type 3) type DLBCL treated with CHOP or CHOP like regimen not using rituximab. Methods: We analyzed retrospectively the prognosis between the GC and non-GC types of DLBCL treated with R-CHOP regimen. All 50 patients with DLBCL, diagnosed between July 2003 and July 2005 were included in this study. The pathology was reviewed by hematopathologist and confirmed to be de novo DLBCL according to the WHO classification. Patients with primary CNS- and post-transplant lymphomas were excluded. GC type or non-GC type DLBCL was determined by immunohistochemistry such as the expression patterns of CD10, BCL-6, and IRF-4 (MUM1). All patients were initially treated with six cycles of R-CHOP regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. If we evaluated partial response after six cycles of R-CHOP, the patients have added radiation therapy. Results: The patients consisted of 30 GC type and 20 non-GC type DLBCL with a median age of 61.0 yr (range 31–83 yr). The median follow up of surviving patients was 24 months. CR rate between GC and non-GC types were 57.0% vs. 75.0%, p=0.186, and overall response rate were 87.0% vs. 90.0%, p=0.929, respectively. The median of progression free survival was 17.3 months vs. 19.6 months, p=0.80. There is no statistical significance difference between two groups. Conclusion: These results suggest that addition of rituximab to CHOP regimen improves clinical outcome of non-GC type DLBCL as well as GC type DLBCL.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 2
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    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 3001-3001
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 3001-3001
    Abstract: Many tumor suppressor genes are silenced by epigenetic mechanisms in human cancers, including mantle cell lymphoma (MCL). In this study, we have used a variety of research tools to screen for genes that are epigenetically silenced in MCL. Changes in the global gene expression profile of the MCL cell line, Jeko1, were analyzed after treatment with the combination of the demethylating agent, 5-aza-2′-deoxycytidine, and the histone deacetylase inhibitor, suberoyl anilide bishydroxamide, by DNA microarray technique. By screening over 22,000 genes, we identified 26 candidate tumor suppressor genes, expression of which were enhanced by the treatment, in the MCL line. Basal expression of these 26 genes were low in Jeko1 cells. The treatment enhanced the expression more than 2 folds and the enhancement was also confirmed by real-time PCR. Methylation status of these 26 genes were examined by bisulfite sequencing and/or combined bisulfite and restriction enzyme digestion assay in Jeko1 cells. We found hypermethylation of a CpG island in the middle of the INPP5F gene. We also found the hypermethylation of that region of INPP5F in normal peripheral blood. We also examined expression levels of these 26 genes in normal mantle cells by real-time PCR and found only 11 genes showed high levels of transcription in laser-dissected normal mantle cells. We examined expression of these 11 genes in eight MCL clinical samples by real-time PCR and found that only three genes, INPP5F, DUSP10 and FGD2 showed very low expression levels. We conclude that expression of INPP5F, DUSP10 and FGD2 genes were suppressed in MCL cells although the expression of these genes are high in normal mantle cells. INPP5F is a inositol phosphatase and could be involved in PI3K pathway. DUSP10 is a dual specific phosphatase and could be involved in JNK pathway. FGD2 is a RAS-GAP gene and could be involved in RAS pathway. These three genes may be candidate tumor suppressor genes in MCL and further functional analysis is ongoing.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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  • 3
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2815-2815
    Abstract: Abstract 2815 Backgrounds: Next to diffuse large B-cell lymphoma and follicular lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the third most common subtype of non-Hodgkin's lymphomas. Their clinical course usually is indolent with long-progression free survival (PFS) and overall survival (OS). Because it can involve many sites throughout the body, a patient of MALT lymphoma is often treated by different strategies, radiation therapy, surgery, or chemotherapy. The aims of study are to assess the clinical characteristics and treatment results of this one of the most common lymphoma and to analyze the prognostic factors. Patients and Methods: Ninety-eight patients with MALT lymphoma consecutively diagnosed by an expert hematopathologist from March 2001 to October 2008 were reviewed retrospectively. They all underwent standarlized staging program in our hospital. Majority of the patients had localized disease. Comparisons were performed between patients with gastric and non-gastric MALT lymphoma. Prognostic significance of various factors for PFS was examined. Statistical analyses of PFS and OS were calculated using Kaplan-Meier estimators. Comparison among categories was performed by means of log-rank test. Using Cox proportional hazards regression analysis, multivariate analysis was performed about estimated risk factors. Results: Patients were 48 males and 50 females. Median age was 62 years old (range 26 to 85 years old). Only 17 patients had advanced diseases. 52 had the primary site located in the stomach, and 22 had in the orbit, and 8 had in the salivary grand. Ninety-three patients received some treatment, including radiation, chemotherapy and surgery. Mainly, localized gastric lymphoma and non-gastric lymphoma were performed eradication of Helicobacter Pylori and the radiation therapy respectively. All but two patients with disseminated diseases treated with rituximab-combined chemotherapy. The response rate of the initial treatment was 94%, and the CR rate was 76%. After a median follow-up time of 40 months (range 1 to 109 months), 3-years OS and PFS were 100% and 89%, respectively. 3-year PFS for localized disease and advanced disease were 94% and 73%, respectively. 3-years PFS was 95% for gastric MALT lymphoma and 82% for non-gastric lymphoma. All of the patients with localized gastric MALT lymphoma were progression-free at three years after the treatment. Adverse prognostic factors for PFS were non-gastric lymphoma and disseminated disease. In a multivariate analysis, shorter PFS was associated with non-gastric lymphoma. Discussion: Our analysis indicates that MALT lymphoma is an indolent disease with long survival, but patients with non-gastric lymphoma and advanced diseases were prone to have worse prognosis. H.pilori eradication was an effective first-line treatment for the localized gastric MALT lymphoma and leads to a favorable long term out-come. Rituximab-combined chemotherapy was effective even though for advanced disease. In this rituximab era, clinical course of this indolent lymphoma may become much better. However, the therapeutic strategy of MALT lymphoma is still controversial. We need to assess and clear up which is the best. 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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  • 4
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2814-2814
    Abstract: Abstract 2814 Background: Central nervous system (CNS) relapse is considered an infrequent but severe, nearly fatal complication of diffuse large B-cell lymphoma (DLBCL) following initial chemotherapy. Intrathecal (IT) prophylaxis cannot be recommended for all DLBCL patients because of the low probability of CNS relapse. Rituximab (R) added to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been reported as likely to reduce the frequency of CNS relapse in patients with DLBCL, however, the efficacy of rituximab on the prognosis of CNS relapse compared with those who relapsed at other sites and predictive factors for CNS relapse in patients treated with rituximab contained chemotherapy remain unclear. The main objective was to determine the high-risk patients who need IT prophylaxis and the outcomes of CNS relapse compared with relapse on other sites. Patients and Methods: Diffuse large B cell lymphoma patients treated with rituximab contained CHOP regimen with or without radiotherapy and IT prophylaxis at Cancer Institute Hospital of JFCR between October 2003 and December 2006 were analyzed retrospectively. CNS relapse was defined as leptomeningeal, brain parenchymal, or intradural involvement with lymphoma, based on radiological findings or the presence of malignant lymphoma cells in spinal fluid. Results: A total number of 137 patients were identified. IT prophylaxis was administered in 13 of 137 patients (9.48%) depending on the sites of lymphoma involvement, such as bone marrow involvement, testis, paranasal sinuses. 17 of 137 patients (12.4%) underwent radiotherapy after chemotherapy because of early stage or their residual disease. With a median follow-up period of 4.4 years, 9 patients had experienced CNS relapse (6.7%: 3.0–12.1, 95%CI) among 30 documented relapses, with 9 presenting with nodal relapse alone and 21 presenting with extranodal relapse including CNS. IT prophylaxis and the addition of radiotherapy did not affect the frequency of CNS relapse (P=0.6 and 0.26). Median time to CNS relapse was 20 months. Overall survival (OS) was significantly inferior in CNS relapse patients to other-sites relapse patients, (median OS, 61 months vs. did not occur; P =.042). Nevertheless, OS was not significantly different between patients with CNS relapse or at other sites. In univariate analysis, factors associated with CNS relapse (P 〈 0.05) included age over 65 years and serum levels of soluble IL-2 receptors (sIL-2R) ≧10 ULN (upper limit of normal) but not sex, PS ≧3, stage ≧4, B symptom, bulky mass, elevated LDH 〉 2 ULN, elevated MIB1 index ≧90%, poor revised-international prognostic index (R-IPI), extranodal sites ≧2, or type of GC or non-GC. Multivariate Cox regression analysis identified increased serum levels of (sIL-2R) (P =0.037) as an independent predictive factor for CNS relapse (P=0.04, HR=7.02: 95%CI=1.87-26.22). Five of 9 CNS relapse patients were still alive with the combination treatment of whole brain irradiation, systemic chemotherapy (R- dexamethasone, cisplatin, cytarabine) and intrathecal chemotherapy. Conclusions: The incidence rate of CNS relapse in 137 DLBCL patients treated with R-CHOP, CEOP regimens may be lower than with CHOP in agreement with previous studies. Furthermore, rituximab may improve OS after CNS relapse. Ten times increased serum s-IL2R is a potential independent risk factor for CNS relapse and should be included in the IT prophylaxis indication in patients with DLBCL. 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: 2010
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  • 5
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2678-2678
    Abstract: Abstract 2678 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a wide range of clinical outcomes. Rituximab added to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, R-CHOP has made a marked improvement in outcome in patients with DLBCL. The International Prognostic Index (IPI), which consists of age 〉 60 years, stage III/IV, elevated lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) performance status (PS) † 2, and more than one extranodal (EN) site of disease, remains the most commonly used system for risk classification in DLBCL. However, recent studies suggested that new agent has altered the significance of previously recognized risk factors. Here we investigate the prognostic impact of reported risk factors in a large DLBCL patient cohort in a single institute to determine a better prognostic model in rituximab era. Patients and Methods: In total, 250 newly diagnosed DLBCL patients treated with R-CHOP regimen at the Cancer Institute Hospital of JFCR between October 2003 and December 2008 were included and analyzed. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared among risk groups using the log rank test. The Cox proportional hazards model was used to test the significance of prognostic factors. ROC curve was used to determine optimal serum level of sIL-2R and LDH as a cut off value for 4-year mortality risk. Results: The median age of patients was 65 years (range 23–88 years), 56% were male. The median follow-up time was 49 months (range 1–90 months) and 39 deaths had been recorded by the time of the last follow-up. The IPI still remains predictive with an OS ranging from 52.4% to 91.6% at 4 years; however it cannot discriminate between low and low-intermediate group. Revised IPI was valid as well with an OS ranging from 63.3% to 97%. In univariate analysis, elevated sIL-2R level, B symptom, elevated LDH level, PS 〉 2, age 〉 65, stage III/IV, CD5 positive, and EN 〉 1 were significant as poor prognostic factors whereas sex, bulky mass, MIB1 index 〉 90%, Non-GCB were not. Furthermore, multivariate analysis showed that only sIL-2R 〉 924U/ml, CD5 expression, and EN 〉 1 were significant with relative hazard 1.4∼17.5, 1.4∼8.9, and 1.3∼4.7, respectively. As elevated sIL-2R was the most powerful prognostic factor, we performed further analysis on this parameter. Average serum sIL-2R level was 2,775U/ml (range from 220U/ml to 43,100U/ml) with a normal limit of upper is 230U/ml. ROC curve demonstrated that serum sIL-2R was more optimal value than serum LDH to identify high risk patients for 4-year mortality after initiation of R-CHOP therapy and cutoff value of sIL-2R was 924U/ml (1.73 upper limit of normal). sIL-2R level can be divided into three distinctprognostic groups. Patients with sIL-2R 〈 925U/ml fall into a very good group with a 4-year OS:98% and 4-year PFS:90.7%, patients with 925U/ml 〈 =sIL-2R 〈 4,625U/mlfall into a good group with a 4-year OS:82% and 4-year PFS:77.7%, and patients with sIL-2R 〉 =4,625U/ml fall into a poor group with a 4-year OS:59.6% and 4-year PFS:54.7% (P 〈 0.001). Conclusions: sIL-2R level is an independent and powerful prognostic factor in serum level dependent manner in DLBCL patients treated with R-CHOP. This prognostic model should be reassessed on a larger scale and prospective study. 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: 2011
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  • 6
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3659-3659
    Abstract: Abstract 3659 Introduction Prognostic predictors for newly diagnosed malignant lymphoma, such as International Prognostic Index (IPI), reversed-IPI, Follicular Lymphoma International Prognostic Index (FILIP), and Prognostic Index for peripheral T-cell lymphoma (PIT), are well known. On the other hand, prognostic factors for recurrent or refractory malignant lymphoma have never been reported. Patients and methods We retrospectively analyzed patients with recurrent or refractory malignant lymphoma treated with ICE or DHAP as salvage treatment from April 2005 to June 2010 in our institute. We evaluated five biological parameters; C-reactive protein (CRP), lactate dehydrogenase (LDH), hemoglobin (Hb), beta 2 microglobulin (ƒÀ2m), and soluble interleukin 2 receptor (sIL-2R) before salvage treatment. The cut-off of CRP, LDH, and ƒÀ2m was defined with upper normal limit, that of Hb was defined with lower normal limit, and that of sIL-2R was defined with 1000 IU/L. Primary endpoint was overall survival (OS) after salvage treatments were started. OS was analyzed by Kaplan-Meier method. Biological prognostic factors for OS were evaluated by Cox regression analysis. All reported p values were two-sided, and p 〈 .05 was considered significant. Results 69 patients with recurrent or refractory malignant lymphoma were entered into this study; 50 with recurrent lymphoma, and 19 with refractory lymphoma. On histological examination, 41 were diffuse large B-cell lymphoma (DLBCL), 8 were peripheral T-cell lymphoma-not otherwise specified, 6 were Hodgkin's lymphoma, 6 were angioimmunoblastic T-cell lymphoma, 4 were NK lymphoma, 2 were ALK-negative anaplastic large cell lymphoma, and 2 were follicular lymphoma grade 3b. Median level of CRP, LDH, Hb, ƒÀ2m, and sIL-2R were 0.3 IU/L (range, 0.1 – 26.7 IU/L), 241 IU/L (range, 130 – 6510 IU/L), 11.8 g/L (5.0 – 15.8 g/L), 2.01 IU/L (range, 1.1 – 4.44 IU/L), and 970 IU/L (range, 275 – 7840 IU/L), respectively. 53 patients and 16 patients received ICE and DHAP, respectively. 28 patients were treated with salvage treatment combined with rituximab. After a median follow-up time of 12.3 months (range, 1.3 – 70.8), median OS was 15.6 months (95% CI, 10.6 – 20.6), and there was no significant difference between the ICE arm and the DHAP arm (17.6 months vs 13.6 months, respectively; p =.100). The OS was significantly worse in patients with the following parameters: elevated CRP level (hazard ratio 3.847; p =.015), elevated LDH level (hazard ratio 3.972; p =.009), and anemia (hazard ratio 3.847; p =.014) according to the multivariate analysis. When outcome was plotted according to the numbers of elevated CRP level, elevated LDH level and anemia before salvage treatment, three risk groups emerged. Patients with zero prognostic factors have the best outcome, patients with one or two prognostic factors have moderate outcome, and patients with three prognostic factors have the poorest outcome. We defined these as low risk (L-R), intermediate risk (I-R), and high risk groups (H-R), respectively. The median OS of H-R, I-R, and L-R were 4.7 months (95% CI, 2.1 – 7.3), 17.6 months (95% CI, 12.4 – 22.8), and 63.2 months, respectively. There was a significant difference between H-R, I-R, and L-R (log-rank test; p =.000, Figure 1). Moreover, among the patients with DLBCL, the median OS time of H-R, I-R, and L-R were 4.3 months (95% CI, 0.9 – 7.8), 18.8 months (95% CI, 2.2 – 35.3), and not reached, respectively. There was a significant difference among H-R, I-R, and L-R for patients with DLBCL (log-rank test; p =.001, Figure 2). Among I-R patients in all lymphomas, the OS was significantly longer in the ICE arm than in the DHAP arm (18.8 months vs 13.6 months, respectively; p =.030). Moreover, the OS in I-R patients with DLBCL was longer in the ICE arm than in the DHAP arm significantly (not reached vs 13.6 months, respectively; p =.024). There was no significant difference between the ICE and the DHAP arms with H-R and L-R in both all lymphomas and DLBCL. Conclusion Elevated CRP level, elevated LDH level, and anemia were predictive factors for poorer outcome among patients with recurrent or refractory malignant lymphoma treated with ICE or DHAP. We classified patients into three groups based on these three predictors, and there was a significant difference in OS among H-R, I-R, and L-R in patients with both all lymphomas and DLBCL. ICE predicted better outcome than DHAP in I-R with both all lymphomas and DLBCL. Disclosures: Mishima: Chugai Pharmaceutical Co, Ltd: Consultancy. Yokoyama:Chugai Pharmaceutical Co, Ltd: Consultancy. Hatake:Chugai pharmaceutical co, ltd: Honoraria, Research Funding; Kyowa Hakko Kirin Co, Ltd: Honoraria, Research Funding; Takeda Pharmaceutical Co, Ltd: Honoraria, Research Funding; Pfizer japan Inc: Research Funding; Ono Pharmaceutical Co, Ltd: Honoraria.
    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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  • 7
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4441-4441
    Abstract: 〈 Background 〉 Patients with relapsed and refractory diffuse large B-cell lymphoma are usually treated with platinum-based salvage chemotherapy. We retrospectively analyzed the efficacy of adding rituximab with ICE as a salvage treatment for relapsed and refractory diffuse large B-cell lymphoma. 〈 Method 〉 From November 2003 to December 2006, patients with relapsed or refractory de novo diffuse large B-cell lymphoma represented CD20 positivty who received R-ICE (rituximab375mg/m2, Ifosfamide 1200mg/m2, calboplatin 400mg/m2 and etopside100mg/m2 ), were analyzed retrospectively. 〈 Result 〉 23 patients (19 relapse and 4 reflactory) (M:F=14:9) (median age 69, 28–77) were included. At starting treatment, twelve patients received rituximab and 11 patients were rituximab naive. In all 23 patients, responses were 11 Complete remission (CR), and 6 partial response (PR), resulting in overall response (ORR) was 74.9%. With median follow up of 10.5 months, estimated 1yr-progression free survival (PFS) was 49% and 1yr-overall survival (OS) was 70%.In patients received rituximab, ORR was 66.7% and 5 patiets achieved CR (41.7%).In the without rituximab, ORR was 90.9% and 7 patiets achieved CR (63.6%). No statistical differences were observed in response even with retuximab pretreatment. Estimated 1yr-PFS was 23% and 70% (p=0.0752) and 1yr-OS was 59% and83% (P=0.0049),respectively. NCI-CTC grade 3/4 neutropenia and thrombocytopenia were reported 100% and 91%, For non-hematological adverse event, there were grade 3 liver dysfunction (2/23) and grade 3 arrythmia (1/23). No toxic death was reported in this study. 〈 Conclusion 〉 R-ICE showed promising efficacy with tolelable toxicity. Available date suggested adding rituximab to ICE is more effective for patients not received rituximab in the pretreament.
    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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  • 8
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1611-1611
    Abstract: Abstract 1611 Background: Extranodal natural killer/T-cell lymphoma (ENKL), nasal type, is a recognized a rare distinct entity strongly associated EBV infection, accounting for 3% to 10% of malignant lymphomas in East Asia. Recent studies suggest that concurrent chemoradiotherapy was effective as first-line therapy for patients with localized ENKL, nasal type. We assess treatment results with concurrent chemoradiotherapy for ENKLs. Patients and methods: From December 2007 to July 2010, newly diagnosed localized ENKL, nasal type, and treated with concurrent radiotherapy (median 50 Gy; range 46–56 Gy) and 3 cycles of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) at the Cancer Institute Hospital, Tokyo, Japan were analyzed retrospectively. All the histopathological samples were reviewed according to the WHO classification by expert hematopathologists. Results: Total of sixteen patients was identified. Baseline patients. characteristics included a median age of 56.5 years (range; 30–76 years), eleven men and five women, thirteen patients (81%) with stage IE and three (19%) with stage IIE. For IPI, patients with low and low-intermediate risks were thirteen patients (81%) and three (19%), respectively. For NKIPI, patients with group 1, 2, and 3 were six patients (37%), seven (44%), and three (19%), respectively. All patients received concurrent chemoradiotherapy, and eleven patients (69%) achieved complete remission, with 2 partial remissions. The overall response rate was 81%. At a median follow-up of 17 months (range; 2–44), the 2-year progression-free survival and overall survival rates were 54.7% and 61.1%, respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. Grade 3/4 adverse events were leukopenia (100%), neutropenia (100%), anemia (19%), mucositis (63%), anorexia (81%), and febrile neutropenia (25%), respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. No treatment-related deaths were observed. Conclusions: Concurrent radiotherapy and DeVIC for patients with localized ENKL, nasal type, demonstrated favorable outcomes. We are now investigating what factors indicate good or poor prognosis in this regimen. Progression free survival of concurrent radiotherapy and DeVIC regimen Disclosures: Yokoyama: CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy. Mishima:CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy.
    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
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3697-3697
    Abstract: Abstract 3697 Poster Board III-633 BACKGROUND Originally, rituximab monotherapy for patients with relapsed or refractory aggressive lymphoma was developed with eight weekly cycles of infusions. However, in combination with R-CHOP therapy, it designed a treatment protocol of tri-weekly rituxiamb. Then four phase III studies were also reported of tri-weekly rituximab in combination with CHOP therapy. We hypothesized that a combination of eight dose-dense weekly cycles of rituximab concentrated in early initial therapy, and six cycles of standard CHOP (DR-CHOP) might result in greater improvement than that obtained with tri-weekly standard R-CHOP. PURPOSE To evaluate the clinical outcome of combination with eight dose-dense weekly cycles of rituximab and six cycles of standard CHOP (DR-CHOP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). In addition, the pharmacokinetic (PK) parameter of serum rituximab concentration was analyzed. PATIENTS AND METHODS One hundred twenty-three patients were treated with DR-CHOP regimen in Cancer Institute Hospital from June 2003 to July 2007. All the histopathology samples were reviewed according to the WHO classification by an expert hematopathologist. Patients with transformed lymphomas from indolent B-cell lymphoma were excluded from this study. Baseline patient characteristics included a median age of 66 years (range, 24-88 years), fifty-one patients with low risk International Prognostic Index (IPI), 35 with low-intermediate IPI, 20 with high-intermediate IPI, and 17 with high IPI. In sixteen patients, prospective PK of serum rituximab concentration was analyzed. Treatments Rituximab was administered on day 1, 8, 15, 22, 29, 36, 43, and 50. CHOP followed the administration of rituximab on day 1, 22, and 43. After eight cycles of infusions of rituximab, only CHOP was administered (cycle 4-6). RESULTS At a median follow-up of 38 months, the 3-year progression-free survival and overall survival rates were 80.9% (95% confidence interval [CI], 74.0% to 87.9%) and 85.3% (95% CI, 78.8% to 91.9%), respectively. The treatment was tolerated well, and no grade 5 adverse events were observed. Maximum serum concentration of rituximab (Cmax) was 396±74 mcg /mL on day 50 (after cycle 8 of rituximab). No statistical difference in PK of serum rituximab levels was observed between relapsers and non-relapsers. CONCLUSIONS DR-CHOP was safe, feasible, and promising good clinical outcome regimen for patients with newly diagnosed DLBCL. However, this was a retrospective study, not poerwful enough to deal with efficacy. To confirm these results, larger studies are being planned to estimate the efficacy of DR-CHOP for patients with DLBCL. Now a phase III multicenter study (DR-CHOP versus standard R-CHOP) in Japan is underway. 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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  • 10
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4449-4449
    Abstract: Background: In recent years, it has been reported that addition of rituximab to CHOP chemotherapy significantly improves event-free survival (EFS) and overall survival (OS) compared with standard CHOP alone in patients with diffuse large B-cell lymphoma (DLBCL). On the other hand, gastric DLBCL is a good clinical outcome without surgical excision in the group of primary extranodal DLBCL. Localized gastric DLBCL shows very good EFS and OS treated with standard CHOP plus radiation therapy without rituximab. Methods: We analyzed retrospectively the prognosis between R-CHOP and CHOP alone in patients with localized gastric DLBCL. All 24 patients diagnosed between July 1999 and July 2006 in our hospital, were included in this study. The pathology was reviewed by a hematopathologist and confirmed to be de novo DLBCL according to the WHO classification. The staging system was using by Lugano meeting classification. Patients with stage IIE and IV were excluded. All patients were initially treated with six cycles of CHOP or R-CHOP regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. If we evaluated partial response after six cycles of chemothrapy, the patients have been added radiation therapy. Results: Initial characteristics of the 24 patients are summarized in Table 1. The median age of patients at time of inclusion was 67.5 yr (range 30–83 yr). The median follow up of surviving patients was 30 months. CR rates between CHOP and R-CHOP were 91.7% vs. 83.3%, p=1.000, and overall response rates were 100% vs. 83.3%, p=.478, respectively. 2 years progression-free survival and overall survival were no statistical significance difference between two groups (Log rank test: P=.138, P=.739). Conclusion: These results suggested that addition of rituximab to CHOP chemotherapy does not improve clinical outcome of localized gastric DLBCL. The patients with localized gastric DLBCL did not get the clinical benefits of rituximab. As you know, rituximab needs high costs, so we recommend standard CHOP regimen plus radiation therapy in patients with localized gastric DLBCL, without rituximab combination regimen. Characteristics of the 24 patients with localized gastric DLBCL Characteristic CHOP (n=12) R-CHOP (n=12) P Age 1.000 = 〈 60 3 4 〉 60 9 8 Male 7 6 1.000 Stage (Lugano) .890 I 4 3 II 1 7 9 Unknown 1 0 IPI score .867 0,1 7 7 2 4 5 Unknown 1 0
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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