Adoptive therapy with cytomegalovirus‐specific T cells for cytomegalovirus infection after haploidentical stem cell transplantation and factors affecting efficacy
Adoptive therapy with cytomegalovirus (CMV)‐specific cytotoxic T lymphocytes (CMV‐CTLs) has emerged as an effective method for CMV infection. However, the efficacy reportedly ranges from 50% to 90%, and factors affecting anti‐CMV efficacy have not been established. We investigated the safety and eff...
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Veröffentlicht in: | American journal of hematology 2022-06, Vol.97 (6), p.762-769 |
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creator | Pei, Xu‐Ying Zhao, Xiang‐Yu Liu, Xue‐Fei Mo, Xiao‐Dong Lv, Meng Xu, Lan‐Ping Wang, Yu Chang, Ying‐Jun Zhang, Xiao‐Hui Liu, Kai‐Yan Huang, Xiao‐Jun |
description | Adoptive therapy with cytomegalovirus (CMV)‐specific cytotoxic T lymphocytes (CMV‐CTLs) has emerged as an effective method for CMV infection. However, the efficacy reportedly ranges from 50% to 90%, and factors affecting anti‐CMV efficacy have not been established. We investigated the safety and efficacy of adoptive therapy with CMV‐CTLs for CMV infection in 190 patients after haploidentical stem cell transplantation (haplo‐SCT), and importantly, we analyzed the main factors affecting antiviral efficacy. The CMV peak titer decreased from 19 (range, 1.0–503.0) × 103 copies/mL to 3.9 (range, 0–112) × 103 copies/mL after CMV‐CTL infusion. The cumulative complete response (CR) rates in the first, fourth, and sixth weeks after the first CMV‐CTL infusion were 37.9% (95% CI 35.0–40.8), 76.8% (95% CI 70.7–82.9), and 89.5% (95% CI 85.2–93.8), respectively. In multivariate analysis, persistent CMV infection prior to CMV‐CTL infusion (hazard ratio [HR] 2.29, 95% CI 1.29–4.06, p = .005) and basiliximab treatment within 2 weeks of CMV‐CTL infusion (HR 1.87, 95% CI 1.06–3.81, p = .031) were independent predictors of poor antiviral efficacy of CMV‐CTL therapy. Our data showed that adoptive therapy with CMV‐CTLs is a safe and effective treatment for CMV infection after haplo‐SCT. Persistent CMV infection and basiliximab treatment are correlated with poor anti‐CMV efficacy of CMV‐CTL therapy. |
doi_str_mv | 10.1002/ajh.26535 |
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However, the efficacy reportedly ranges from 50% to 90%, and factors affecting anti‐CMV efficacy have not been established. We investigated the safety and efficacy of adoptive therapy with CMV‐CTLs for CMV infection in 190 patients after haploidentical stem cell transplantation (haplo‐SCT), and importantly, we analyzed the main factors affecting antiviral efficacy. The CMV peak titer decreased from 19 (range, 1.0–503.0) × 103 copies/mL to 3.9 (range, 0–112) × 103 copies/mL after CMV‐CTL infusion. The cumulative complete response (CR) rates in the first, fourth, and sixth weeks after the first CMV‐CTL infusion were 37.9% (95% CI 35.0–40.8), 76.8% (95% CI 70.7–82.9), and 89.5% (95% CI 85.2–93.8), respectively. In multivariate analysis, persistent CMV infection prior to CMV‐CTL infusion (hazard ratio [HR] 2.29, 95% CI 1.29–4.06, p = .005) and basiliximab treatment within 2 weeks of CMV‐CTL infusion (HR 1.87, 95% CI 1.06–3.81, p = .031) were independent predictors of poor antiviral efficacy of CMV‐CTL therapy. Our data showed that adoptive therapy with CMV‐CTLs is a safe and effective treatment for CMV infection after haplo‐SCT. Persistent CMV infection and basiliximab treatment are correlated with poor anti‐CMV efficacy of CMV‐CTL therapy.</description><identifier>ISSN: 0361-8609</identifier><identifier>EISSN: 1096-8652</identifier><identifier>DOI: 10.1002/ajh.26535</identifier><identifier>PMID: 35293011</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Antiviral Agents - therapeutic use ; Basiliximab - therapeutic use ; Cytomegalovirus ; Cytomegalovirus Infections - etiology ; Cytomegalovirus Infections - therapy ; Cytotoxicity ; Hematology ; Hematopoietic Stem Cell Transplantation - adverse effects ; Humans ; Infections ; Lymphocytes T ; Multivariate analysis ; Persistent infection ; Stem Cell Transplantation ; T-Lymphocytes, Cytotoxic</subject><ispartof>American journal of hematology, 2022-06, Vol.97 (6), p.762-769</ispartof><rights>2022 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3535-5caa14878b6652e91de85f211d8c41be25e16c8562995cd86f475793d22385633</citedby><cites>FETCH-LOGICAL-c3535-5caa14878b6652e91de85f211d8c41be25e16c8562995cd86f475793d22385633</cites><orcidid>0000-0003-1253-7465 ; 0000-0002-9881-7945 ; 0000-0002-8139-1773 ; 0000-0003-0245-6792 ; 0000-0002-6124-6050 ; 0000-0003-1200-7763 ; 0000-0002-6751-7827 ; 0000-0002-2145-6643</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fajh.26535$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fajh.26535$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35293011$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pei, Xu‐Ying</creatorcontrib><creatorcontrib>Zhao, Xiang‐Yu</creatorcontrib><creatorcontrib>Liu, Xue‐Fei</creatorcontrib><creatorcontrib>Mo, Xiao‐Dong</creatorcontrib><creatorcontrib>Lv, Meng</creatorcontrib><creatorcontrib>Xu, Lan‐Ping</creatorcontrib><creatorcontrib>Wang, Yu</creatorcontrib><creatorcontrib>Chang, Ying‐Jun</creatorcontrib><creatorcontrib>Zhang, Xiao‐Hui</creatorcontrib><creatorcontrib>Liu, Kai‐Yan</creatorcontrib><creatorcontrib>Huang, Xiao‐Jun</creatorcontrib><title>Adoptive therapy with cytomegalovirus‐specific T cells for cytomegalovirus infection after haploidentical stem cell transplantation and factors affecting efficacy</title><title>American journal of hematology</title><addtitle>Am J Hematol</addtitle><description>Adoptive therapy with cytomegalovirus (CMV)‐specific cytotoxic T lymphocytes (CMV‐CTLs) has emerged as an effective method for CMV infection. However, the efficacy reportedly ranges from 50% to 90%, and factors affecting anti‐CMV efficacy have not been established. We investigated the safety and efficacy of adoptive therapy with CMV‐CTLs for CMV infection in 190 patients after haploidentical stem cell transplantation (haplo‐SCT), and importantly, we analyzed the main factors affecting antiviral efficacy. The CMV peak titer decreased from 19 (range, 1.0–503.0) × 103 copies/mL to 3.9 (range, 0–112) × 103 copies/mL after CMV‐CTL infusion. The cumulative complete response (CR) rates in the first, fourth, and sixth weeks after the first CMV‐CTL infusion were 37.9% (95% CI 35.0–40.8), 76.8% (95% CI 70.7–82.9), and 89.5% (95% CI 85.2–93.8), respectively. In multivariate analysis, persistent CMV infection prior to CMV‐CTL infusion (hazard ratio [HR] 2.29, 95% CI 1.29–4.06, p = .005) and basiliximab treatment within 2 weeks of CMV‐CTL infusion (HR 1.87, 95% CI 1.06–3.81, p = .031) were independent predictors of poor antiviral efficacy of CMV‐CTL therapy. Our data showed that adoptive therapy with CMV‐CTLs is a safe and effective treatment for CMV infection after haplo‐SCT. Persistent CMV infection and basiliximab treatment are correlated with poor anti‐CMV efficacy of CMV‐CTL therapy.</description><subject>Antiviral Agents - therapeutic use</subject><subject>Basiliximab - therapeutic use</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus Infections - etiology</subject><subject>Cytomegalovirus Infections - therapy</subject><subject>Cytotoxicity</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Humans</subject><subject>Infections</subject><subject>Lymphocytes T</subject><subject>Multivariate analysis</subject><subject>Persistent infection</subject><subject>Stem Cell Transplantation</subject><subject>T-Lymphocytes, Cytotoxic</subject><issn>0361-8609</issn><issn>1096-8652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9u1DAQxi1ERZfCgRdAlrjAYVv_iR3nuKqAgir1Us6R1xl3vUrsYDutcuMReAiejCfB3ZQeKvU0Hus338ynD6F3lJxSQtiZ3u9OmRRcvEArShq5VlKwl2hFuKTlTZpj9DqlPSGUVoq8QsdcsIaXboX-bLowZncLOO8g6nHGdy7vsJlzGOBG9-HWxSn9_fU7jWCcdQZfYwN9n7AN8SmGnbdgsgsea5sh4p0e--A68NkZ3eOUYThM4xy1T2OvfdYL7jtstckhpjJ6EPE3GGxZqM38Bh1Z3Sd4-1BP0I8vn6_PL9aXV1-_nW8u14YX82thtC4Ga7WVxT80tAMlLKO0U6aiW2ACqDRKSNY0wnRK2qoWdcM7xnj55fwEfVx0xxh-TpByO7h0f6_2EKbUMlkRUilKVEE_PEH3YYq-XFcoocqCumaF-rRQJoaUIth2jG7QcW4pae-ja0t07SG6wr5_UJy2A3SP5P-sCnC2AHeuh_l5pXbz_WKR_AcBqabe</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Pei, Xu‐Ying</creator><creator>Zhao, Xiang‐Yu</creator><creator>Liu, Xue‐Fei</creator><creator>Mo, Xiao‐Dong</creator><creator>Lv, Meng</creator><creator>Xu, Lan‐Ping</creator><creator>Wang, Yu</creator><creator>Chang, Ying‐Jun</creator><creator>Zhang, Xiao‐Hui</creator><creator>Liu, Kai‐Yan</creator><creator>Huang, Xiao‐Jun</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><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>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1253-7465</orcidid><orcidid>https://orcid.org/0000-0002-9881-7945</orcidid><orcidid>https://orcid.org/0000-0002-8139-1773</orcidid><orcidid>https://orcid.org/0000-0003-0245-6792</orcidid><orcidid>https://orcid.org/0000-0002-6124-6050</orcidid><orcidid>https://orcid.org/0000-0003-1200-7763</orcidid><orcidid>https://orcid.org/0000-0002-6751-7827</orcidid><orcidid>https://orcid.org/0000-0002-2145-6643</orcidid></search><sort><creationdate>20220601</creationdate><title>Adoptive therapy with cytomegalovirus‐specific T cells for cytomegalovirus infection after haploidentical stem cell transplantation and factors affecting efficacy</title><author>Pei, Xu‐Ying ; 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However, the efficacy reportedly ranges from 50% to 90%, and factors affecting anti‐CMV efficacy have not been established. We investigated the safety and efficacy of adoptive therapy with CMV‐CTLs for CMV infection in 190 patients after haploidentical stem cell transplantation (haplo‐SCT), and importantly, we analyzed the main factors affecting antiviral efficacy. The CMV peak titer decreased from 19 (range, 1.0–503.0) × 103 copies/mL to 3.9 (range, 0–112) × 103 copies/mL after CMV‐CTL infusion. The cumulative complete response (CR) rates in the first, fourth, and sixth weeks after the first CMV‐CTL infusion were 37.9% (95% CI 35.0–40.8), 76.8% (95% CI 70.7–82.9), and 89.5% (95% CI 85.2–93.8), respectively. In multivariate analysis, persistent CMV infection prior to CMV‐CTL infusion (hazard ratio [HR] 2.29, 95% CI 1.29–4.06, p = .005) and basiliximab treatment within 2 weeks of CMV‐CTL infusion (HR 1.87, 95% CI 1.06–3.81, p = .031) were independent predictors of poor antiviral efficacy of CMV‐CTL therapy. Our data showed that adoptive therapy with CMV‐CTLs is a safe and effective treatment for CMV infection after haplo‐SCT. Persistent CMV infection and basiliximab treatment are correlated with poor anti‐CMV efficacy of CMV‐CTL therapy.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>35293011</pmid><doi>10.1002/ajh.26535</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-1253-7465</orcidid><orcidid>https://orcid.org/0000-0002-9881-7945</orcidid><orcidid>https://orcid.org/0000-0002-8139-1773</orcidid><orcidid>https://orcid.org/0000-0003-0245-6792</orcidid><orcidid>https://orcid.org/0000-0002-6124-6050</orcidid><orcidid>https://orcid.org/0000-0003-1200-7763</orcidid><orcidid>https://orcid.org/0000-0002-6751-7827</orcidid><orcidid>https://orcid.org/0000-0002-2145-6643</orcidid></addata></record> |
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subjects | Antiviral Agents - therapeutic use Basiliximab - therapeutic use Cytomegalovirus Cytomegalovirus Infections - etiology Cytomegalovirus Infections - therapy Cytotoxicity Hematology Hematopoietic Stem Cell Transplantation - adverse effects Humans Infections Lymphocytes T Multivariate analysis Persistent infection Stem Cell Transplantation T-Lymphocytes, Cytotoxic |
title | Adoptive therapy with cytomegalovirus‐specific T cells for cytomegalovirus infection after haploidentical stem cell transplantation and factors affecting efficacy |
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