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      The Prognostic Role of Circulating Epstein-Barr Virus DNA Copy Number in Angioimmunoblastic T-Cell Lymphoma Treated with Dose-Adjusted EPOCH

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      https://www.riss.kr/link?id=A105988266

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      다국어 초록 (Multilingual Abstract)

      Purpose Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens.
      Materials and Methods Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen.
      Results Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNApositive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median followup was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressivefree survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNApositive and EBV DNAnegative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNApositive group than in the EBV DNAnegative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response.
      Conclusion Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.
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      Purpose Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide...

      Purpose Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens.
      Materials and Methods Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen.
      Results Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNApositive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median followup was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressivefree survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNApositive and EBV DNAnegative group (hazard ratio [HR], 2.24; 95% CI, 1.15 to 4.35; p=0.006), but also worse OS was observed in the pretreatment EBV DNApositive group than in the EBV DNAnegative group (HR, 2.74; 95% CI, 1.22 to 6.19; p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17; 95% CI, 1.17 to 4.00; p=0.014) and OS (HR, 3.24; 95% CI, 1.48 to 7.11; p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response.
      Conclusion Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients.

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      참고문헌 (Reference)

      1 Swerdlow SH, "WHO classication of tumours of haematopoietic and lymphoid tissues" IARC Press 2008

      2 Chen Y, "The clinical significance of Epstein-Barr virus DNA in peripheral blood mononuclear cells in patients with non-Hodgkin lymphoma" 58 : 2349-2355, 2017

      3 Delfau-Larue MH, "Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma : a clinicobiological study of the GELA" 97 : 1594-1602, 2012

      4 Huang J, "Sequential development of diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma" 40 : 346-351, 2012

      5 Cheson BD, "Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group" 17 : 1244-, 1999

      6 Liang JH, "Prognostic impact of Epstein-Barr virus(EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia" 7 : 2135-2142, 2016

      7 Ito Y, "Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type" 18 : 4183-4190, 2012

      8 Karakas T, "Peripheral T-cell lymphomas respond well to vincristine, adriamycin, cyclophosphamide, prednisone and etoposide(VACPE)and have a similar outcome as high-grade B-cell lymphomas" 24 : 121-129, 1996

      9 Lai GM, "P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines" 49 : 696-703, 1991

      10 Nickelsen M, "High-dose CHOP plus etoposide(Mega-CHOEP)in T-cell lymphoma : a comparative analysis of patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group(DSHNHL)" 20 : 1977-1984, 2009

      1 Swerdlow SH, "WHO classication of tumours of haematopoietic and lymphoid tissues" IARC Press 2008

      2 Chen Y, "The clinical significance of Epstein-Barr virus DNA in peripheral blood mononuclear cells in patients with non-Hodgkin lymphoma" 58 : 2349-2355, 2017

      3 Delfau-Larue MH, "Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma : a clinicobiological study of the GELA" 97 : 1594-1602, 2012

      4 Huang J, "Sequential development of diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma" 40 : 346-351, 2012

      5 Cheson BD, "Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group" 17 : 1244-, 1999

      6 Liang JH, "Prognostic impact of Epstein-Barr virus(EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia" 7 : 2135-2142, 2016

      7 Ito Y, "Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type" 18 : 4183-4190, 2012

      8 Karakas T, "Peripheral T-cell lymphomas respond well to vincristine, adriamycin, cyclophosphamide, prednisone and etoposide(VACPE)and have a similar outcome as high-grade B-cell lymphomas" 24 : 121-129, 1996

      9 Lai GM, "P-glycoprotein expression and schedule dependence of adriamycin cytotoxicity in human colon carcinoma cell lines" 49 : 696-703, 1991

      10 Nickelsen M, "High-dose CHOP plus etoposide(Mega-CHOEP)in T-cell lymphoma : a comparative analysis of patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group(DSHNHL)" 20 : 1977-1984, 2009

      11 Vinuesa CG, "Follicular B helper T cells in antibody responses and autoimmunity" 5 : 853-865, 2005

      12 Liang JH, "Epstein-Barr virus(EBV)DNA in whole blood as a superior prognostic and monitoring factor than EBV-encoded small RNA in situ hybridization in diffuse large B-cell lymphoma" 21 : 596-602, 2015

      13 Liang JH, "Efficacy of pegaspargase, etoposide, methotrexate and dexam-ethasone in newly diagnosed advanced-stage extra-nodal natural killer/T-cell lymphoma with the analysis of the prognosis of whole blood EBV-DNA" 7 : e608-, 2017

      14 Wilson WH, "Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas : a pharmacodynamic approach with high efficacy" 99 : 2685-2693, 2002

      15 Weiss LM, "Detection and localization of Epstein-Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma" 79 : 1789-1795, 1992

      16 Federico M, "Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma : analysis of the international peripheral T-cell lymphoma project" 31 : 240-246, 2013

      17 Mourad N, "Clinical, biologic, and pathologic features in 157patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials" 111 : 4463-4470, 2008

      18 Advani RH, "Cardiac toxicity associated with bevacizumab(Avastin)in combination with CHOP chemotherapy for peripheral T cell lymphoma in ECOG 2404 trial" 53 : 718-720, 2012

      19 Ganjoo K, "Bevacizumab and cyclosphosphamide, doxorubicin, vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms : an Eastern Cooperative Oncology Group study(E2404)" 55 : 768-772, 2014

      20 Hsu SM, "Autocrine and paracrine functions of cytokines in malignant lymphomas" 48 : 433-444, 1994

      21 Zhou Y, "Angioimmunoblastic T-cell lymphoma : histological progression associates with EBV and HHV6B viral load" 138 : 44-53, 2007

      22 de Leval L, "Advances in the understanding and management of angioimmunoblastic T-cell lymphoma" 148 : 673-689, 2010

      23 Kim SJ, "A prognostic index for natural killer cell lymphoma after nonanthracycline-based treatment : a multicentre, retrospective analysis" 17 : 389-400, 2016

      24 International Non-Hodgkin's Lymphoma Prognostic Factors Project, "A predictive model for aggressive non-Hodgkin's lymphoma" 329 : 987-994, 1993

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