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  • 1
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3053-3053
    Abstract: Introduction Tumors deregulate immunological antitumor response, resulting in survival of tumor cells, which implicate the existence of immunological tolerance to tumors.CD4+ T cells activate tumor-specific cytotoxic CD8+ T cells via cytokines and they also can eliminate cancer in the absence of CD8+ T cell. Absolute CD4+ T-cell count(ACD4C)in biopsied specimen is known to correlate with therapeutic outcomes in DLBCL. In patients with solid cancer, CD4+ T cells decrease in the peripheral blood, whereas regulatory T cells (Tregs) increase in the peripheral blood.Tregshave a role to reduce antibody dependent cellular toxicity (ADCC) of rituximab against CD20+ B-cell malignancies. On the other hand,we and othersknow that absolute lymphocyte count in peripheral blood can predict survival of diffuse large B-cell lymphoma (DLBCL). It has been indefinite, however, which lymphocyte including CD4+ T cells in peripheral blood reflect the prognosis of DLBCL. Method We enrolled patients who were diagnosed with de novo DLBCL from 2006 until 2013, received R-CHOP, and followed up at Cancer Institute Hospital, Tokyo, Japan. We had measured absolute lymphocyte count, T-cell ratio, CD4+ T-cell ratio, and CD8+ T-cell ratio in these patients using pretreatment blood samples. Data were collected prospectively and recorded into a computerized database. All patientsgave written informed consent allowing the use of their medical record. The optimal cut-off values were made based on its utility as a marker for death using box plot, clinical important value from references, and receiver operating characteristic curve. Differences between the results of comparative tests were considered significant if the two-sided P value was less than 0.05. Results A total of 355 patients were diagnosed with de novo DLBCL.Baseline characteristics were following: median age was 65 (range 20-89), Patients aged over 60 were 243 (68%), male to female ratio was 1.2, ECOG PS ≥ 2 of 19 (5%), elevated LDH of 152 (43%), low ACD4C ( 〈 350 x 106 /l) of 119 (34%), low ACD8C ( 〈 300 x 106 /l) of 144 (41%), CD5+ DLBCL of 38 (11%), Ann Arbor stage III/IV of 145 (41%), and involved extranodal sites ≥ 2 of 93 (26%). Germinal center B cell (GCB) DLBCL was seen in 167 (53%), non-GCB DLBCL was seen in 148 (47%). Patients without evidence of death (n = 282) at last follow-up had a higher ACD4C (≥ 350 x 106 /l) at diagnosis than those with death (n = 73) (P 〈 0.0001). There was also markedly difference in absolute CD8+ T-cell count, but no difference in absolute B-cell count. At the median follow-up of 57 months, Kaplan-Meier method estimated that 5-year PFS was 78.1% in the high ACD4C group and 62.0% in the low ACD4C group (Figure 1A, log-rank P 〈 0.001), whereas 67.4% in the high ACD8C group and 41.6% in the low ACD8C group (P = 0.01). Furthermore, 5-year OS was 83.6% in the high ACD4C group and 64.5% in the low ACD4C group (Figure 1B, log-rank P 〈 0.001), whereas 56.2% in the high ACD8C group and 36.1% in the low ACD8C group (P 〈 0.01). An ACD4C 〈 350 x 106 /l was identified as an adverse prognostic marker in DLBCL by Cox hazard model (hazard ratio 1.9, P = 0.01). In addition, CD5+ DLBCL, PS ≥ 2, stage III/IV, and non-GCB DLBCL were identified as low ACD4C. Age 〉 60, extranodal diseases ≥ 2, and elevated LDH were not identified in this study. ACD4C had negative correlation with tumor burden, which was shown by Pearsonfs coefficient (correlation with LDH; r = -0.24, P 〈 0.0001) and Studentfs t-test (correlation with stage; P 〈 0.0001). Interestingly, low ACD4C affected OS only in the stage III/IV, non-GCB DLBCL, and high-IPI groups (fisherfs exact test P 〈 0.01). Baseline characteristics of the low ACD4C group showed higher rate of stage III/IV (P 〈 0.001), elevated LDH (P 〈 0.01), extranodal disease ≥ 2 (P 〈 0.001), soluble IL-2 receptor 〉 2000 U/l (P 〈 0.001), low serum albumin (P = 0.001), and beta2 microglobulin 〉 2 mg/dl (P 〈 0.001). Conclusion This study demonstrates that ACD4C had a negative correlation with tumor burden and low ACD4C at diagnosis made worse prognosis of patients with DLBCL, in particular, those who had high tumor burden, non-GCB, or high IPI at diagnosis, suggestingTregsmight increase in peripheral blood in the low ACD4C group and might impair the ADCC of rituximab. Figure 1 Figure 1. Disclosures Terui: Yanssen: Honoraria. Mishima:Chugai: Consultancy. Nishimura:Chugai: Consultancy. Yokoyama:Chugai: Consultancy. Hatake:Meiji-Seika: Consultancy; Kyowa Kirin: Honoraria, Research Funding; Chugai: Research Funding; Otsuka: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 2
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5554-5554
    Abstract: Introduction: Myelodysplastic syndromes (MDS) are clonal hematopoietic neoplasms characterized by abnormal maturation of precursor cells which often translates into peripheral blood cytopenias and a high rate of transformation to acute myeloid leukemia (AML) due to accumulation of genetic alterations. The AZA-001 trial showed azacitidine (AZA) significantly prolonged median overall survival compared with conventional care regimens (24.5 vs 15.0 months; P=0.0001). AZA is standard first-line treatment for Intermediate-2 and High-risk myelodysplastic syndrome patients who are not immediate candidates for allogeneic stem cell transplantation, but this study included no cases of therapy related MDS (t-MDS). T-MDS is known to have poor prognosis, therefore it is very important to analyze the outcome of patients with t-MDS treated in the front-line with AZA. Methods: We studied newly diagnosed 29 MDS patients who were treated by AZA in our hospital from July, 2010 to April, 2016, retrospectively. AZA was given subcutaneously at 75 mg/㎡per day for 5 or 7 days every 28 days. Results: We analyzed 29 MDS patients. According to the WHO classification, there were 12 RA, 15 RCMD, 10 RAEB-1, 2 RAEB 2 and 1 MDS-U. The median age was 70 year (range 49-88), and men was 12 (41.3%). There were 12 de novoMDS cases (41.3%) and 17 t-MDS cases (58.6%). All of the t-MDS patients had previously received chemotherapy (17 patients, 100%) and 9 patients had also received radiotherapy (9 patients, 53%). Very poor risk group was 47.1% (9/17) in t-MDS group compared to 25.0% (3/12) in de novo MDS group (P=0.26). Median follow up time was 11.4 months (range 1.4-47.8). Twenty five patients (86.3%) were treated by AZA for 5 days. Four patients (13.7%) were treated by AZA for 7 days, but all 4 patients decreased the dosing period to 5 days due to unacceptable toxicity. AZA was given for a median of 4 cycles (range 1-33). In 29 MDS patients, 1-year overall survival (OS) was 60.5% (95% CI, 38.7-76.7%) and 1-year PFS was 40.1% (95% CI, 18.8-60.6%). After a median follow-up of 11.4 months, median OS was 18.7 months (95% CI, 9.4-21). One-year OS was 59.3% in t-MDS group compared to 63.6% in de novo MDS group (P=0.294). 1-year PFS was 38.4% in t-MDS group compared to 40.4% in de novo MDS group (P=0.626). One-year OS was 37.5% in very poor risk karyotype group (R-IPSS) compared to 74.6% in not very poor risk karyotype group (P=0.000748). 1-year PFS was 43.2% in very poor risk karyotype group compared to 39.0% in not very poor risk karyotype group (P=0.594). Focusing on t-MDS group, 1-year OS was 46.9% in very poor risk karyotype group (8/17 47%) compared to 74.1% in not very poor risk karyotype group (9/17 53%) (P=0.054). 1-year PFS was 48.0% in very poor risk karyotype group compared to 26.0% in not very poor risk karyotype group (P=0.339). Conclusions: In our study, 1-year OS in all MDS patients was 60.5%. It was slightly poor prognosis than 1-year OS in AZA-001 trial (about 70%). Our study include t-MDS cases (58.6%). Additionally, AZA was given for a median of 4 cycles in our study but 6 cycles in the AZA-001 trial. It showed severe patient's background of our study. These difference may cause the lower median OS and poorer prognosis. There trended to be more patients who had very poor risk karyotype in t-MDS group, but there was no significant difference between t-MDS and de novoMDS for the 1-year OS and PFS. Azacitidin is effective in the therapy related myelodysplastic syndrome. Disclosures Yokoyama: Chugai: Consultancy. Mishima:Chugai: Consultancy. Nishimura:Chugai: Consultancy. Terui:Yanssen: Honoraria. Hatake:Kyowa Kirin: Honoraria, Research Funding; Chugai: Research Funding; Otsuka: Consultancy; Meiji-Seika: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 3
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5081-5081
    Abstract: Introduction Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma (NHL) accounting for 5 percent of NHLs. Most patients with MCL are 60 years of age and older. The prognosis of patients with MCL is moderately aggressive and variable; the median overall survival is 3-5years. MCL international prognostic index(MIPI)is related to prognosis of the patients with MCL, however, it is unclear whether MIPI predicts outcomes of MCL over sixties. Out therapeutic strategy in elderly patients with newly diagnostic MCL is not high-dose chemotherapy with autologous stem cell transplantation. Instead of aggressive chemotherapy, Rituximab maintenance is considered as an effective and feasible option. Thus, we investigated whether MCL international prognostic index (MIPI) relates overall survival (OS) or progression free survival (PFS), and whether maintenance therapy with Rituximab improved OS or PFS in patients with newly diagnosed MCL patients 60 and older. Methods We analyzed retrospectively 60 years of age and older patients with MCL who have achieved complete response (CR) or partial response (PR) after induction chemotherapy with rituximab at our hospital from December 2005 to February 2015. Two of primary refractory patients were excluded because analysis is for patients who are eligible for rituximab maintenance therapy. The patients were diagnosed by hematopathologist in our hospital. According to the MIPI, patients were stratified into low risk (0 patients, 0%), intermediate risk (9 patients, 41%), and high risk (13 patients, 59 %). Induction chemotherapy regimens were six cycles of R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone), four cycle of R-hyper CVAD/MA (rituximab-cyclophosphamide-vincristine-doxorubicin-dexamethasone alternating with rituximab-methotrexate-cytarabine), six cycles of R-CVP (rituximab- cyclophosphamide-vincristine-predonisone), R-VP16 (rituximab-etoposide), or six cycles of VR-CAP (bortezomib-rituximab-cyclophosphamide-doxorubicin- predonisone). Rituximab maintenance therapy started 6 months after the last induction chemotherapy and underwent four weekly infusion every 6 months for 2 years. Results A total of 22 MCL patients were analyzed. The number of patients who had achieved CR was 14 and PR was 8. 14 of 22 patients were treated rituximab maintenance. Median age was 73 years old. MIPI could predict OS of MCL. 3-year-OS was significantly superior intermediate risk to MIPI high risk (3-years-OS: 87.5 %vs.51.9 %,p=0.0232), whereas PFS didn't have correlation with MIPI(3-years PFS70.0 %vs.38.5 %,p=0.136). 3-years OS was significantly superior maintenance group to no maintenance group (3-years survival rate 91.7 % vs. 25.0 %, p=0.00188, figure 1), and 3-years PFS tend to improve in the maintenance group (3-years PFS, 65.8 % vs.25.0 %, p=0.0773, figure 2). Conclusion: In this study, MIPI correlates with OS, however doesn't show with PFS. Rituximab maintenance therapy is effective, and prolongs OS for 60 years of age and older patients with MCL. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Nishimura: Chugai Pharmaceutical CO., LTD.: Consultancy. Mishima:Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.
    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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  • 4
    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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  • 5
    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
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 6
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4221-4221
    Abstract: Background: Introduction of Rituximab has shown a remarkable improvement on survival for the patients with diffuse Large B cell Lymphoma (DLBCL). However, involvement of central nervous system (CNS) at relapse in these patients is still an issue and a mostly fatal with a median survival of 2.5 - 4 months when they treated with conventional therapies. The Memorial Sloan - Kettering Cancer Center (MSKCC) prognostic score has been used as a statistically powerful model to patients with newly diagnosed primary central nervous system lymphoma (PCNSL) before rituximab introduction. By contrast, effective prognostic model for the relapsed DLBCL patients with CNS involvement in the rituximab era is unclear. The purpose of this study was to address treatment response and detailed prognosis of CNS recurrence of DLBCL after initial treatment with Rituximab contained chemotherapy. Patients and Methods: In total, 560 newly diagnosed de novo DLBCL patients treated with R- Results: Among the 25 patients assessed in this study, median age was 61 years (range, 34-81 years) at relapse.Sixteen (64%) patients were male. Primary sites at initial diagnosis were mostly extra-nodal sites such as nasal cavity, paranasal sinuses, skin, primary effusion, breasts, testes, ovaries, gastro-intestine, kidneys, adrenal glands, and bone in 88% (22/25) of the patients. The cell of origin of germinal center (GC) subtype by Hans algorithm were shown in 47.6% (10/25). All patients other than one with stage I were to receive 6 to 8 cycles of R-CHOP and the patient with stage I were to receive combined modality therapy with 3 cycles of R-CHOP followed by involved field radiation therapy as an initial treatment. Only two patients received intrathecal prophylaxis. The median interval between the initial diagnosis and CNS relapse was 22 months (range, 1-100 months). The patients status at relapse were 44% of (11/25) first complete response (CR), 32% of (8/25) first partial response (PR), 20% (5/25) of second CR, and 4% (1/25) of second PR after the latest chemotherapy. There were 15 patients (60%) with brain intra- parenchymal lesions identified by brain imaging and the others (40%) with leptomeningeal infiltration revealed with cerebrospinal fluid analysis. Front-line treatment for relapse at CNS lesion was chemotherapy with or without whole brain radiotherapy (WBRT) in 13 patients (52%). A total of 6 patients (24%) received WBRT without chemotherapy. The others received the best supportive care. In addition, most patients through those three groups received intrathecal chemotherapy with MTX, Ara-C, and prednisone. The median overall survival (OS) after CNS relapse was 7 months (95% CI: 5-12) for the whole population, 12 months for chemotherapy group, 6.5 months for WBRT group, and 2 months for BSC group (p = 0.02). To date 22 patients (88%) had died. At univariate analysis significant prognostic factors for overall survival were age at relapse (P=0.02), elevated b2- microglobulin (b2-MG) (p=0.03), and response for the latest chemotherapy (p=0.01) that was only a significant factor in multivariate analysis. Thus we established Relapsed-MSKCC prognostic score consisting of age 〈 50, KPS 〉 =70, and response for the latest chemotherapy; add 1 to MSKCC score if they did not achieve CR after the latest therapy. The median OS in patients with a R-MSKCC prognostic score of 1 was not reached, and differed significantly from the 13 months in patients with a R-MSKCC score of 2, 8 months in patients with a R-MSKCC score of 3, and 2 months in patients with a R-MSKCC score of 4 (P=0.01). Conclusions: The Survival of CNS recurrence in patients with DLBCL remains lethal. R-MSKCC prognostic score may predict survival better in these patients. Figure Figure. Disclosures Nishimura: Chugai pharmaceutical co.LTD: Consultancy. Terui:Yanssen: Honoraria. Mishima:Chugai: Consultancy. Yokoyama:Chugai: Consultancy. Hatake:Meiji-Seika: Consultancy; Kyowa Kirin: Honoraria, Research Funding; Otsuka: Consultancy; Chugai: 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: 2016
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  • 7
    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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  • 8
    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
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    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
    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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  • 10
    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
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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