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  • American Society of Hematology  (3)
  • Tsuyama, Naoko  (3)
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  • American Society of Hematology  (3)
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  • 1
    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
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 2
    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
    Location Call Number Limitation Availability
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  • 3
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1541-1541
    Abstract: Abstract 1541 Introduction Thymidine kinase (TK) activity has been investigated as a prognostic factor in hematological malignancies, and several studies have demonstrated that a high TK activity correlates with the disease stage and provides prognostic information on overall survival (OS) and progression free survival (PFS). However, the prognostic significance of TK activity for patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP has not been investigated yet. The purpose of this retrospective study was to investigate the prognostic value of high TK activity compared with other laboratory findings in evaluating OS in patients undergoing R-CHOP for previously untreated DLBCL. Methods We retrospectively analyzed patients treated with R-CHOP for previously untreated DLBCL from September 2003 to October 2008 in our institute. We evaluated serum TK activity, C-reactive protein (CRP), lactate dehydrogenase (LDH), and hemoglobin (Hb) before R-CHOP. The cut-off for TK activity was defined as 14 IU/L. The cut-offs for CRP and LDH were defined as the upper normal limits, and the cut-off for Hb was defined as the lower normal limit. The primary endpoint was OS. The OS and PFS were analyzed by the Kaplan-Meier method, and biological prognostic factors for OS were evaluated by Cox regression analysis. Second, complete response (CR) rate was assessed by the chi square test and Fisher's exact test, comparing patients with and without the prognostic factors. All p-values reported were two-sided, and statistical significance was defined as p 〈 0.05. Results The clinical records of 242 patients with previously untreated DLBCL were analyzed in this study. The median age of the patients was 65.2 years old (range, 23.2 – 88.1). The median levels of TK activity, CRP, LDH, and Hb were 14.0 IU/L (range, 3.0 – 1100), 0.3 IU/L (range, 0.1 – 21.2), 254.5 IU/L (range, 111.0 – 44432), and 13.1 g/dL (range, 7.7 – 17.0), respectively. Median follow-up time for all patients was 53.0 months. Median OS was 82.3 months (95% CI, 78.6 – 86.0). The OS was significantly worse in patients with high TK activity (p =.001) and anemia (p =.006) by univariate analysis. Median OS in the high and low TK activity groups was 71.7 months (95% CI 63.9 – 79.4) and 85.9 months (95% CI 81.8 – 89.9). In multivariate analysis, the OS was significantly worse in patients with high TK activity (HR 2.640, 95% CI 1.018 – 6.881; p =.046) and anemia (HR 2.228, 95% CI 1.000 – 4.967; p =.050). Median PFS was 73.9 months (95% CI, 69.4 – 78.4). The PFS was significantly worse in patients with high TK activity (p =.000), anemia (p =.005), and high LDH level (p =.010) by univariate analysis. Median PFS in the high and low TK activity groups was 57.3 months (95% CI 48.7 – 66.0) and 80.9 months (95% CI 75.5 – 86.2). In multivariate analysis, PFS was significantly worse in patients with high TK activity (HR 2.809, 95% CI 1.375 – 5.737; p =.005) and anemia (HR 1.902, 95% CI 1.033 – 3.504; p =.039). The CR and overall response rates were 81.4% and 93.0%, respectively. The OS was significantly better in patients who achieved CR than those with partial response or less. Median OS in the CR and non-CR groups was 86.1 months (95% CI 82.7 – 89.5) and 66.0 months (95% CI 53.6 – 78.3), respectively (p 〈 .001). According to the chi square test and Fisher's exact test, the CR rates of patients with high TK activity (p 〈 .001), high CRP (p =.004), and high LDH (p =.019) were significantly worse. The CR rates in the high and low TK activity groups were 68.9% and 92.5%, respectively. The OS for patients with high TK activity who did not achieve CR was even significantly worse than that of both low TK activity patients who did not achieve CR and high TK activity patients who achieved CR (p =.047 and 〈 .001). However, the OS was similar in high and low TK activity group patients who achieved CR (p =.171, Figure 1). Conclusion High TK activity significantly worsened OS and PFS among patients with previously untreated DLBCL who had undergone R-CHOP. While we commonly perform R-CHOP for DLBCL as an initial treatment, our findings show that the OS becomes significantly worse in patients who do not achieve CR by R-CHOP. The OS in patients with high TK activity who did not achieve CR was significantly worse than that with both low TK activity patients who did not achieve CR and high TK activity patients who achieved CR. Our findings suggest that novel treatment strategies for previously untreated DLBCL patients with high TK activity are certainly necessary. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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