High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies
High-risk chronic lymphocytic leukemia (CLL) has been defined by clinical and/or genetic resistance (TP53 abnormalities) to treatment with chemoimmunotherapy (CIT). With the availability of pathway inhibitors (PIs), such as kinase inhibitors and BCL2 antagonists, the outlook of CIT-resistant patient...
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| Veröffentlicht in: | Blood 2018-08, Vol.132 (9), p.892-902 |
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| creator | Dreger, Peter Ghia, Paolo Schetelig, Johannes van Gelder, Michel Kimby, Eva Michallet, Mauricette Moreno, Carol Robak, Tadeusz Stilgenbauer, Stephan Montserrat, Emili on behalf of the European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT) |
| description | High-risk chronic lymphocytic leukemia (CLL) has been defined by clinical and/or genetic resistance (TP53 abnormalities) to treatment with chemoimmunotherapy (CIT). With the availability of pathway inhibitors (PIs), such as kinase inhibitors and BCL2 antagonists, the outlook of CIT-resistant patients has dramatically improved. Here, we propose a revision of the concept of high-risk CLL, driven by TP53 abnormalities and response to treatment with PI. CLL high-risk-I, CIT-resistant is defined by clinically CIT-resistant disease with TP53 aberrations, but fully responsive to PI. This category is largely the domain of PI-based therapy, and cellular therapy (ie, allogeneic hematopoietic cell transplantation) remains an option only in selected patients with low individual procedure-related risk. In CLL high-risk-II, CIT- and PI-resistant, characterized by increasing exhaustion of pharmacological treatment possibilities, cellular therapies (including chimeric antigen receptor-engineered T cells) should be considered in patients eligible for these procedures. Moreover, molecular and cellular therapies are not mutually exclusive and could be used synergistically to exploit their full potential.
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| doi_str_mv | 10.1182/blood-2018-01-826008 |
| format | Article |
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[Display omitted]</description><identifier>ISSN: 0006-4971</identifier><identifier>ISSN: 1528-0020</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2018-01-826008</identifier><identifier>PMID: 29997221</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adoptive Transfer ; Allografts ; Drug Resistance, Neoplasm - genetics ; Drug Resistance, Neoplasm - immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - immunology ; Leukemia, Lymphocytic, Chronic, B-Cell - mortality ; Leukemia, Lymphocytic, Chronic, B-Cell - therapy ; Medicin och hälsovetenskap</subject><ispartof>Blood, 2018-08, Vol.132 (9), p.892-902</ispartof><rights>2018 American Society of Hematology</rights><rights>2018 by The American Society of Hematology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-768fd17c26cccd2573986000f6c3ee559649ea4064e2452d2709c4f2be2d512f3</citedby><cites>FETCH-LOGICAL-c496t-768fd17c26cccd2573986000f6c3ee559649ea4064e2452d2709c4f2be2d512f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29997221$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:138998777$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Dreger, Peter</creatorcontrib><creatorcontrib>Ghia, Paolo</creatorcontrib><creatorcontrib>Schetelig, Johannes</creatorcontrib><creatorcontrib>van Gelder, Michel</creatorcontrib><creatorcontrib>Kimby, Eva</creatorcontrib><creatorcontrib>Michallet, Mauricette</creatorcontrib><creatorcontrib>Moreno, Carol</creatorcontrib><creatorcontrib>Robak, Tadeusz</creatorcontrib><creatorcontrib>Stilgenbauer, Stephan</creatorcontrib><creatorcontrib>Montserrat, Emili</creatorcontrib><creatorcontrib>on behalf of the European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)</creatorcontrib><creatorcontrib>European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)</creatorcontrib><title>High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies</title><title>Blood</title><addtitle>Blood</addtitle><description>High-risk chronic lymphocytic leukemia (CLL) has been defined by clinical and/or genetic resistance (TP53 abnormalities) to treatment with chemoimmunotherapy (CIT). With the availability of pathway inhibitors (PIs), such as kinase inhibitors and BCL2 antagonists, the outlook of CIT-resistant patients has dramatically improved. Here, we propose a revision of the concept of high-risk CLL, driven by TP53 abnormalities and response to treatment with PI. CLL high-risk-I, CIT-resistant is defined by clinically CIT-resistant disease with TP53 aberrations, but fully responsive to PI. This category is largely the domain of PI-based therapy, and cellular therapy (ie, allogeneic hematopoietic cell transplantation) remains an option only in selected patients with low individual procedure-related risk. In CLL high-risk-II, CIT- and PI-resistant, characterized by increasing exhaustion of pharmacological treatment possibilities, cellular therapies (including chimeric antigen receptor-engineered T cells) should be considered in patients eligible for these procedures. Moreover, molecular and cellular therapies are not mutually exclusive and could be used synergistically to exploit their full potential.
[Display omitted]</description><subject>Adoptive Transfer</subject><subject>Allografts</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Drug Resistance, Neoplasm - immunology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Humans</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - mortality</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - therapy</subject><subject>Medicin och hälsovetenskap</subject><issn>0006-4971</issn><issn>1528-0020</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v1DAQxS0EokvhGyDkI5eA7Tj-wwEJVUCRKnGBs-XYk43ZJA520mq_Pd5mW05w8nj0e_M08xB6Tck7ShV73w4x-ooRqipCK8UEIeoJ2tGGlQZh5CnaEUJExbWkF-hFzr8IobxmzXN0wbTWkjG6Q-t12PdVCvmAXZ_iFBwejuPcR3dcTjWsBxiDxWHCSw8YksWxw7Nd-jt7LN0-tGGJKX8o9QL7ZJcw7fEYB3DrYBO2k8cOhuH-UyYkOwfIL9Gzzg4ZXp3fS_Tzy-cfV9fVzfev364-3VSOa7FUUqjOU-mYcM551shaq7Im6YSrAZpGC67BciI4MN4wzyTRjnesBeYbyrr6ElXb3HwH89qaOYXRpqOJNphz61AqMFxJUovC63_yc4r-r-hBSGultZJSFu3bTVvA3yvkxYwhn1a3E8Q1G0aE0oyrmhaUb6hLMecE3aMRJeYUrrkP15zCNYSaLdwie3N2WNsR_KPoIc0CfNwAKDe9DZBMdgEmBz4kcIvxMfzf4Q-hu7kb</recordid><startdate>20180830</startdate><enddate>20180830</enddate><creator>Dreger, Peter</creator><creator>Ghia, Paolo</creator><creator>Schetelig, Johannes</creator><creator>van Gelder, Michel</creator><creator>Kimby, Eva</creator><creator>Michallet, Mauricette</creator><creator>Moreno, Carol</creator><creator>Robak, Tadeusz</creator><creator>Stilgenbauer, Stephan</creator><creator>Montserrat, Emili</creator><creator>on behalf of the European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20180830</creationdate><title>High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies</title><author>Dreger, Peter ; Ghia, Paolo ; Schetelig, Johannes ; van Gelder, Michel ; Kimby, Eva ; Michallet, Mauricette ; Moreno, Carol ; Robak, Tadeusz ; Stilgenbauer, Stephan ; Montserrat, Emili ; on behalf of the European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-768fd17c26cccd2573986000f6c3ee559649ea4064e2452d2709c4f2be2d512f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adoptive Transfer</topic><topic>Allografts</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Drug Resistance, Neoplasm - immunology</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Humans</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - immunology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - mortality</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - therapy</topic><topic>Medicin och hälsovetenskap</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dreger, Peter</creatorcontrib><creatorcontrib>Ghia, Paolo</creatorcontrib><creatorcontrib>Schetelig, Johannes</creatorcontrib><creatorcontrib>van Gelder, Michel</creatorcontrib><creatorcontrib>Kimby, Eva</creatorcontrib><creatorcontrib>Michallet, Mauricette</creatorcontrib><creatorcontrib>Moreno, Carol</creatorcontrib><creatorcontrib>Robak, Tadeusz</creatorcontrib><creatorcontrib>Stilgenbauer, Stephan</creatorcontrib><creatorcontrib>Montserrat, Emili</creatorcontrib><creatorcontrib>on behalf of the European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)</creatorcontrib><creatorcontrib>European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dreger, Peter</au><au>Ghia, Paolo</au><au>Schetelig, Johannes</au><au>van Gelder, Michel</au><au>Kimby, Eva</au><au>Michallet, Mauricette</au><au>Moreno, Carol</au><au>Robak, Tadeusz</au><au>Stilgenbauer, Stephan</au><au>Montserrat, Emili</au><au>on behalf of the European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)</au><aucorp>European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2018-08-30</date><risdate>2018</risdate><volume>132</volume><issue>9</issue><spage>892</spage><epage>902</epage><pages>892-902</pages><issn>0006-4971</issn><issn>1528-0020</issn><eissn>1528-0020</eissn><abstract>High-risk chronic lymphocytic leukemia (CLL) has been defined by clinical and/or genetic resistance (TP53 abnormalities) to treatment with chemoimmunotherapy (CIT). With the availability of pathway inhibitors (PIs), such as kinase inhibitors and BCL2 antagonists, the outlook of CIT-resistant patients has dramatically improved. Here, we propose a revision of the concept of high-risk CLL, driven by TP53 abnormalities and response to treatment with PI. CLL high-risk-I, CIT-resistant is defined by clinically CIT-resistant disease with TP53 aberrations, but fully responsive to PI. This category is largely the domain of PI-based therapy, and cellular therapy (ie, allogeneic hematopoietic cell transplantation) remains an option only in selected patients with low individual procedure-related risk. In CLL high-risk-II, CIT- and PI-resistant, characterized by increasing exhaustion of pharmacological treatment possibilities, cellular therapies (including chimeric antigen receptor-engineered T cells) should be considered in patients eligible for these procedures. Moreover, molecular and cellular therapies are not mutually exclusive and could be used synergistically to exploit their full potential.
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| ispartof | Blood, 2018-08, Vol.132 (9), p.892-902 |
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| subjects | Adoptive Transfer Allografts Drug Resistance, Neoplasm - genetics Drug Resistance, Neoplasm - immunology Hematopoietic Stem Cell Transplantation Humans Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - immunology Leukemia, Lymphocytic, Chronic, B-Cell - mortality Leukemia, Lymphocytic, Chronic, B-Cell - therapy Medicin och hälsovetenskap |
| title | High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies |
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