Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin's disease : an independent biological prognostic marker
Recently, we demonstrated that the presence of high percentages of activated cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's disease (HD) and ALK negative anaplastic large cell lymphoma (ALCL) is associated with a poor prognosis. To test whether this biological prognostic f...
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| Veröffentlicht in: | Leukemia 2001-03, Vol.15 (3), p.458-464 |
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| creator | TEN BERGE, R. L OUDEJANS, J. J DUKERS, D. F MEIJER, J. W. R OSSENKOPPELE, G. J MEIJER, Cjlm |
| description | Recently, we demonstrated that the presence of high percentages of activated cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's disease (HD) and ALK negative anaplastic large cell lymphoma (ALCL) is associated with a poor prognosis. To test whether this biological prognostic factor is more important in predicting clinical outcome than histological diagnosis or clinical factors, we compared the prognostic value of these parameters in an expanded group of classical HD and ALK negative ALCL. Tumor biopsies of classical HD (n = 83) and ALK negative systemic nodal ALCL (n = 43) were investigated for the presence of activated CTLs by immunohistochemistry, using a monoclonal antibody directed against granzyme B. Percentages of activated CTLs were quantified using Q-PRODIT, and their prognostic value was compared to that of histological diagnosis and clinical parameters, including age and stage. Both in classical HD and ALK negative ALCL, a high percentage of activated CTLs (ie > or = 15%) identified a group of patients with poor overall and progression-free survival time, even when adjusted for stage. In multivariate analysis, percentage of activated CTLs remained a strong independent prognostic marker, and was more sensitive than histological diagnosis or clinical factors in predicting overall survival time. We conclude that a high percentage of activated CTLs in the reactive infiltrate of ALK negative ALCL and classical HD is a strong indicator for an unfavorable clinical outcome, regardless of histological diagnosis or clinical parameters. As such, this biological parameter may be an especially helpful tool to determine therapeutic strategies in cases in which the differentiation between ALK negative ALCL and HD remains difficult. |
| doi_str_mv | 10.1038/sj.leu.2402045 |
| format | Article |
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L ; OUDEJANS, J. J ; DUKERS, D. F ; MEIJER, J. W. R ; OSSENKOPPELE, G. J ; MEIJER, Cjlm</creator><creatorcontrib>TEN BERGE, R. L ; OUDEJANS, J. J ; DUKERS, D. F ; MEIJER, J. W. R ; OSSENKOPPELE, G. J ; MEIJER, Cjlm</creatorcontrib><description>Recently, we demonstrated that the presence of high percentages of activated cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's disease (HD) and ALK negative anaplastic large cell lymphoma (ALCL) is associated with a poor prognosis. To test whether this biological prognostic factor is more important in predicting clinical outcome than histological diagnosis or clinical factors, we compared the prognostic value of these parameters in an expanded group of classical HD and ALK negative ALCL. Tumor biopsies of classical HD (n = 83) and ALK negative systemic nodal ALCL (n = 43) were investigated for the presence of activated CTLs by immunohistochemistry, using a monoclonal antibody directed against granzyme B. Percentages of activated CTLs were quantified using Q-PRODIT, and their prognostic value was compared to that of histological diagnosis and clinical parameters, including age and stage. Both in classical HD and ALK negative ALCL, a high percentage of activated CTLs (ie > or = 15%) identified a group of patients with poor overall and progression-free survival time, even when adjusted for stage. In multivariate analysis, percentage of activated CTLs remained a strong independent prognostic marker, and was more sensitive than histological diagnosis or clinical factors in predicting overall survival time. We conclude that a high percentage of activated CTLs in the reactive infiltrate of ALK negative ALCL and classical HD is a strong indicator for an unfavorable clinical outcome, regardless of histological diagnosis or clinical parameters. As such, this biological parameter may be an especially helpful tool to determine therapeutic strategies in cases in which the differentiation between ALK negative ALCL and HD remains difficult.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2402045</identifier><identifier>PMID: 11237071</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anaplastic large-cell lymphoma ; Biological and medical sciences ; Biomarkers, Tumor - analysis ; Biopsy ; Child ; Clinical outcomes ; Cytotoxicity ; Diagnosis ; Female ; Granzyme B ; Granzymes ; Hematologic and hematopoietic diseases ; Hodgkin Disease - immunology ; Hodgkin Disease - metabolism ; Hodgkin's lymphoma ; Humans ; Immunohistochemistry ; Kinases ; Leukemia ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lymphocyte Activation ; Lymphocytes ; Lymphocytes T ; Lymphoma ; Lymphoma, Large B-Cell, Diffuse - immunology ; Lymphoma, Large B-Cell, Diffuse - metabolism ; Male ; Markers ; Medical prognosis ; Medical sciences ; Middle Aged ; Monoclonal antibodies ; Multivariate analysis ; Parameters ; Pathology ; Prognosis ; Serine Endopeptidases - metabolism ; Survival ; Survival Analysis ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - metabolism ; Tumor necrosis factor-TNF ; Tumors</subject><ispartof>Leukemia, 2001-03, Vol.15 (3), p.458-464</ispartof><rights>2001 INIST-CNRS</rights><rights>COPYRIGHT 2001 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2001</rights><rights>Macmillan Publishers Limited 2001.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-eb0b2396f7c3f410fb3914a25e3a9068f0b4e6f9e25f24d88b34462541cbbf233</citedby><cites>FETCH-LOGICAL-c503t-eb0b2396f7c3f410fb3914a25e3a9068f0b4e6f9e25f24d88b34462541cbbf233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>309,310,314,780,784,789,790,23928,23929,25138,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=967952$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11237071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TEN BERGE, R. L</creatorcontrib><creatorcontrib>OUDEJANS, J. J</creatorcontrib><creatorcontrib>DUKERS, D. F</creatorcontrib><creatorcontrib>MEIJER, J. W. R</creatorcontrib><creatorcontrib>OSSENKOPPELE, G. J</creatorcontrib><creatorcontrib>MEIJER, Cjlm</creatorcontrib><title>Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin's disease : an independent biological prognostic marker</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>Recently, we demonstrated that the presence of high percentages of activated cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's disease (HD) and ALK negative anaplastic large cell lymphoma (ALCL) is associated with a poor prognosis. To test whether this biological prognostic factor is more important in predicting clinical outcome than histological diagnosis or clinical factors, we compared the prognostic value of these parameters in an expanded group of classical HD and ALK negative ALCL. Tumor biopsies of classical HD (n = 83) and ALK negative systemic nodal ALCL (n = 43) were investigated for the presence of activated CTLs by immunohistochemistry, using a monoclonal antibody directed against granzyme B. Percentages of activated CTLs were quantified using Q-PRODIT, and their prognostic value was compared to that of histological diagnosis and clinical parameters, including age and stage. Both in classical HD and ALK negative ALCL, a high percentage of activated CTLs (ie > or = 15%) identified a group of patients with poor overall and progression-free survival time, even when adjusted for stage. In multivariate analysis, percentage of activated CTLs remained a strong independent prognostic marker, and was more sensitive than histological diagnosis or clinical factors in predicting overall survival time. We conclude that a high percentage of activated CTLs in the reactive infiltrate of ALK negative ALCL and classical HD is a strong indicator for an unfavorable clinical outcome, regardless of histological diagnosis or clinical parameters. As such, this biological parameter may be an especially helpful tool to determine therapeutic strategies in cases in which the differentiation between ALK negative ALCL and HD remains difficult.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anaplastic large-cell lymphoma</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biopsy</subject><subject>Child</subject><subject>Clinical outcomes</subject><subject>Cytotoxicity</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Granzyme B</subject><subject>Granzymes</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hodgkin Disease - immunology</subject><subject>Hodgkin Disease - metabolism</subject><subject>Hodgkin's lymphoma</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Lymphoma, Large B-Cell, Diffuse - immunology</subject><subject>Lymphoma, Large B-Cell, Diffuse - metabolism</subject><subject>Male</subject><subject>Markers</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Multivariate analysis</subject><subject>Parameters</subject><subject>Pathology</subject><subject>Prognosis</subject><subject>Serine Endopeptidases - metabolism</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumors</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkl1rFDEUhgdRbK3eeilBoV7Nms_58K4UtUJBL-p1yGROdrPNJGuSEfeH-H_N2MVWqUgggXOe901Ozqmq5wSvCGbdm7RdOZhXlGOKuXhQHRPeNrUQgjysjnHXtXXTU35UPUlpi_GSbB5XR4RQ1uKWHFc_PkPU4LNaAwoGKZ3tN5VhRHqfQw7frUZXtdtPu00oEUjIeqS82jmVcsk5FYtQg3PoBppUSY_oIozra-tfJzTaBCoBelviRTzCDsrmMxpscGFttXJoF8Pah1-Gk4rXEJ9Wj4xyCZ4dzpPqy_t3V-cX9eWnDx_Pzy5rLTDLNQx4oKxvTKuZ4QSbgfWEKyqAqR43ncEDh8b0QIWhfOy6gXHeUMGJHgZDGTupTm98ywu-zpCynGxaqlEewpxki5uGc9H-FyRd-U3SL-Crv8BtmKMvRUjaFCdC-xYX6uU_KYqX7lFya7VWDqT1JuSo9HKvPKOll4yJtivU6h6qrBEmq4MHY0v8D8HpHcEGlMubFNycbfDpXmcdQ0oRjNxFW_qzlwTLZfhk2soyfPIwfEXw4lDVPEww3uKHabvzOSqVvpuovLbpN9c3bS8o-wm_V-DR</recordid><startdate>20010301</startdate><enddate>20010301</enddate><creator>TEN BERGE, R. 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lymphocyte Activation</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Lymphoma, Large B-Cell, Diffuse - immunology</topic><topic>Lymphoma, Large B-Cell, Diffuse - metabolism</topic><topic>Male</topic><topic>Markers</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Multivariate analysis</topic><topic>Parameters</topic><topic>Pathology</topic><topic>Prognosis</topic><topic>Serine Endopeptidases - metabolism</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - metabolism</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TEN BERGE, R. L</creatorcontrib><creatorcontrib>OUDEJANS, J. 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L</au><au>OUDEJANS, J. J</au><au>DUKERS, D. F</au><au>MEIJER, J. W. R</au><au>OSSENKOPPELE, G. J</au><au>MEIJER, Cjlm</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin's disease : an independent biological prognostic marker</atitle><jtitle>Leukemia</jtitle><addtitle>Leukemia</addtitle><date>2001-03-01</date><risdate>2001</risdate><volume>15</volume><issue>3</issue><spage>458</spage><epage>464</epage><pages>458-464</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>Recently, we demonstrated that the presence of high percentages of activated cytotoxic T-lymphocytes (CTLs) in biopsy specimens of both Hodgkin's disease (HD) and ALK negative anaplastic large cell lymphoma (ALCL) is associated with a poor prognosis. To test whether this biological prognostic factor is more important in predicting clinical outcome than histological diagnosis or clinical factors, we compared the prognostic value of these parameters in an expanded group of classical HD and ALK negative ALCL. Tumor biopsies of classical HD (n = 83) and ALK negative systemic nodal ALCL (n = 43) were investigated for the presence of activated CTLs by immunohistochemistry, using a monoclonal antibody directed against granzyme B. Percentages of activated CTLs were quantified using Q-PRODIT, and their prognostic value was compared to that of histological diagnosis and clinical parameters, including age and stage. Both in classical HD and ALK negative ALCL, a high percentage of activated CTLs (ie > or = 15%) identified a group of patients with poor overall and progression-free survival time, even when adjusted for stage. In multivariate analysis, percentage of activated CTLs remained a strong independent prognostic marker, and was more sensitive than histological diagnosis or clinical factors in predicting overall survival time. We conclude that a high percentage of activated CTLs in the reactive infiltrate of ALK negative ALCL and classical HD is a strong indicator for an unfavorable clinical outcome, regardless of histological diagnosis or clinical parameters. As such, this biological parameter may be an especially helpful tool to determine therapeutic strategies in cases in which the differentiation between ALK negative ALCL and HD remains difficult.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>11237071</pmid><doi>10.1038/sj.leu.2402045</doi><tpages>7</tpages></addata></record> |
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| ispartof | Leukemia, 2001-03, Vol.15 (3), p.458-464 |
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| subjects | Adolescent Adult Aged Aged, 80 and over Anaplastic large-cell lymphoma Biological and medical sciences Biomarkers, Tumor - analysis Biopsy Child Clinical outcomes Cytotoxicity Diagnosis Female Granzyme B Granzymes Hematologic and hematopoietic diseases Hodgkin Disease - immunology Hodgkin Disease - metabolism Hodgkin's lymphoma Humans Immunohistochemistry Kinases Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymphocyte Activation Lymphocytes Lymphocytes T Lymphoma Lymphoma, Large B-Cell, Diffuse - immunology Lymphoma, Large B-Cell, Diffuse - metabolism Male Markers Medical prognosis Medical sciences Middle Aged Monoclonal antibodies Multivariate analysis Parameters Pathology Prognosis Serine Endopeptidases - metabolism Survival Survival Analysis T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism Tumor necrosis factor-TNF Tumors |
| title | Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin's disease : an independent biological prognostic marker |
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