{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T02:10:45Z","timestamp":1774577445495,"version":"3.50.1"},"reference-count":28,"publisher":"American Society of Hematology","issue":"24","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,12,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>HIV-associated lymphomas (HALs) have high rates of latent infection by gammaherpesviruses (GHVs). We hypothesized that proteasome inhibition would induce lytic activation of GHVs and inhibit HIV infectivity via preservation of cytidine deaminase APOBEC3G, improving lymphoma control. We tested this oncolytic and antiviral strategy by using bortezomib combined with ifosfamide, carboplatin, and etoposide (ICE) alone or with rituximab (ICE\/R) in relapsed\/refractory HAL. A 3+3 dose-escalation design was used with a 7-day lead-in period of single-agent bortezomib. Bortezomib was administered intravenously on days 1 and 8 of each cycle at 1 of 4 dose levels: 0.7, 1.0, 1.3, or 1.5 mg\/m2. ICE began day 8 of cycle 1 and day 1 of subsequent cycles. Rituximab was included on day 1 of cycles 2 to 6 for CD20+ lymphomas. Twenty-three patients were enrolled. The maximum tolerated dose of bortezomib was not reached. Grade 4 toxicities attributable to bortezomib were limited to myelosuppression. Responses occurred in 17 (77%) of 22 patients receiving any protocol therapy. The 1-year overall survival was 57%. After bortezomib alone, both patients with Kaposi sarcoma herpesvirus (KSHV)\u2013positive lymphoma had more than a 1-log increase in KSHV viral load. In 12 patients with Epstein-Barr virus (EBV)\u2013positive lymphoma, median values of EBV viral load increased. Undetectable HIV viremia at baseline in the majority of patients limited evaluation of HIV inhibition. APOBEC3G levels increased in 75% of evaluable patients. Bortezomib combined with ICE\/R in patients with relapsed\/refractory HAL is feasible with response and survival comparing favorably against previously reported second-line therapies. Changes in GHV viral loads and APOBEC3G levels trended as hypothesized. This trial was registered at www.clinicaltrials.gov as #NCT00598169.<\/jats:p>","DOI":"10.1182\/bloodadvances.2018022095","type":"journal-article","created":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T20:04:19Z","timestamp":1545336259000},"page":"3618-3626","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":14,"title":["Safety and efficacy of an oncolytic viral strategy using bortezomib with ICE\/R in relapsed\/refractory HIV-positive lymphomas"],"prefix":"10.1182","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4029-8641","authenticated-orcid":false,"given":"Erin G.","family":"Reid","sequence":"first","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Looney","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA;"},{"name":"Veterans Affairs San Diego Healthcare System, San Diego, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3062-5250","authenticated-orcid":false,"given":"Frank","family":"Maldarelli","sequence":"additional","affiliation":[{"name":"HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-4898","authenticated-orcid":false,"given":"Ariela","family":"Noy","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY;"},{"name":"Department of Hematology, Weill Cornell Medical College, New York, NY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Henry","sequence":"additional","affiliation":[{"name":"Pennsylvania Hospital, Philadelphia, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6752-3530","authenticated-orcid":false,"given":"David","family":"Aboulafia","sequence":"additional","affiliation":[{"name":"Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center, Seattle, WA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3769-6035","authenticated-orcid":false,"given":"Juan Carlos","family":"Ramos","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-2010","authenticated-orcid":false,"given":"Joseph","family":"Sparano","sequence":"additional","affiliation":[{"name":"Montefiore Medical Center, Bronx, NY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard F.","family":"Ambinder","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeannette","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethel","family":"Cesarman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Weill Cornell Medical College, New York, NY; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Yahyaei","sequence":"additional","affiliation":[{"name":"Department of Pathology, Weill Cornell Medical College, New York, NY; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Mitsuyasu","sequence":"additional","affiliation":[{"name":"Center for AIDS Research and Education, University of California, Los Angeles, Los Angeles, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8918-9687","authenticated-orcid":false,"given":"William","family":"Wachsman","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA;"},{"name":"Veterans Affairs San Diego Healthcare System, San Diego, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2018,12,20]]},"reference":[{"issue":"4","key":"2020021109101813200_B1","doi-asserted-by":"crossref","first-page":"dju503","DOI":"10.1093\/jnci\/dju503","article-title":"Excess cancers among HIV-infected people in the United States","volume":"107","author":"Robbins","year":"2015","journal-title":"J Natl Cancer Inst"},{"issue":"11","key":"2020021109101813200_B2","doi-asserted-by":"crossref","first-page":"e495","DOI":"10.1016\/S2352-3018(17)30125-X","article-title":"Cancer risk in HIV-infected people in the USA from 1996 to 2012: a population-based, registry-linkage study","volume":"4","author":"Hern\u00e1ndez-Ram\u00edrez","year":"2017","journal-title":"Lancet HIV"},{"issue":"2","key":"2020021109101813200_B3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s11908-010-0092-5","article-title":"Update on HHV-8-associated malignancies","volume":"12","author":"Sunil","year":"2010","journal-title":"Curr Infect Dis Rep"},{"issue":"5-6","key":"2020021109101813200_B4","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3109\/10428199809057564","article-title":"Expression of Epstein-Barr virus latent genes and adhesion molecules in AIDS-related non-Hodgkin\u2019s lymphomas: correlation with histology and CD4-cell number","volume":"30","author":"Kersten","year":"1998","journal-title":"Leuk Lymphoma"},{"issue":"15","key":"2020021109101813200_B5","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1182\/blood-2009-08-231613","article-title":"Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma","volume":"115","author":"Sparano","year":"2010","journal-title":"Blood"},{"issue":"16","key":"2020021109101813200_B6","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1002\/cncr.26723","article-title":"Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma","volume":"118","author":"Barta","year":"2012","journal-title":"Cancer"},{"issue":"33","key":"2020021109101813200_B7","doi-asserted-by":"crossref","first-page":"4111","DOI":"10.1200\/JCO.2011.41.4193","article-title":"HIV status does not influence outcome in patients with classical Hodgkin lymphoma treated with chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine in the highly active antiretroviral therapy era","volume":"30","author":"Montoto","year":"2012","journal-title":"J Clin Oncol"},{"issue":"8","key":"2020021109101813200_B8","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1182\/blood-2015-08-664706","article-title":"Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803\/AMC 071 trial","volume":"128","author":"Alvarnas","year":"2016","journal-title":"Blood"},{"issue":"12","key":"2020021109101813200_B9","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.3109\/10428194.2012.697559","article-title":"Outcome of patients with relapsed\/refractory acquired immune deficiency syndrome-related lymphoma diagnosed 1999-2008 and treated with curative intent in the AIDS Malignancy Consortium","volume":"53","author":"Bayraktar","year":"2012","journal-title":"Leuk Lymphoma"},{"issue":"10","key":"2020021109101813200_B10","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1056\/NEJMoa1412096","article-title":"Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma","volume":"372","author":"Robak","year":"2015","journal-title":"N Engl J Med"},{"issue":"4","key":"2020021109101813200_B11","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1200\/JCO.2005.02.050","article-title":"Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin\u2019s lymphoma and mantle cell lymphoma","volume":"23","author":"O\u2019Connor","year":"2005","journal-title":"J Clin Oncol"},{"issue":"5","key":"2020021109101813200_B12","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1158\/1078-0432.CCR-06-2295","article-title":"Virus-associated tumor imaging by induction of viral gene expression","volume":"13","author":"Fu","year":"2007","journal-title":"Clin Cancer Res"},{"issue":"10","key":"2020021109101813200_B13","doi-asserted-by":"crossref","first-page":"e116","DOI":"10.1371\/journal.ppat.0020116","article-title":"EC5S ubiquitin complex is recruited by KSHV latent antigen LANA for degradation of the VHL and p53 tumor suppressors","volume":"2","author":"Cai","year":"2006","journal-title":"PLoS Pathog"},{"issue":"6944","key":"2020021109101813200_B14","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nature01709","article-title":"Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts","volume":"424","author":"Mangeat","year":"2003","journal-title":"Nature"},{"issue":"9","key":"2020021109101813200_B15","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.1074\/jbc.M313093200","article-title":"Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway","volume":"279","author":"Mehle","year":"2004","journal-title":"J Biol Chem"},{"issue":"suppl 1","key":"2020021109101813200_B16","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1007\/s00280-002-0446-2","article-title":"Risk-adapted therapy for relapsed and refractory lymphoma using ICE chemotherapy","volume":"49","author":"Moskowitz","year":"2002","journal-title":"Cancer Chemother Pharmacol"},{"issue":"7247","key":"2020021109101813200_B17","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nature07968","article-title":"Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma","volume":"459","author":"Compagno","year":"2009","journal-title":"Nature"},{"issue":"1","key":"2020021109101813200_B18","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1182\/blood-2003-05-1545","article-title":"Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray","volume":"103","author":"Hans","year":"2004","journal-title":"Blood"},{"issue":"5","key":"2020021109101813200_B19","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1200\/JCO.2006.09.2403","article-title":"Revised response criteria for malignant lymphoma","volume":"25","author":"Cheson","year":"2007","journal-title":"J Clin Oncol"},{"issue":"3","key":"2020021109101813200_B20","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1200\/JCO.1993.11.3.570","article-title":"The Functional Assessment of Cancer Therapy scale: development and validation of the general measure","volume":"11","author":"Cella","year":"1993","journal-title":"J Clin Oncol"},{"key":"2020021109101813200_B21","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/978-1-62703-670-2_20","article-title":"Single-copy quantification of HIV-1 in clinical samples","volume":"1087","author":"Wiegand","year":"2014","journal-title":"Methods Mol Biol"},{"issue":"4","key":"2020021109101813200_B22","doi-asserted-by":"crossref","first-page":"329","DOI":"10.5414\/CP202714","article-title":"Efficacy and safety of subcutaneous versus intravenous bortezomib in multiple myeloma: a meta-analysis","volume":"55","author":"Hu","year":"2017","journal-title":"Int J Clin Pharmacol Ther"},{"issue":"10","key":"2020021109101813200_B23","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1002\/(SICI)1097-0142(19960515)77:10<2127::AID-CNCR25>3.0.CO;2-W","article-title":"Second-line chemotherapy in human immunodeficiency virus-related non-Hodgkin\u2019s lymphoma: evidence of activity of a combination of etoposide, mitoxantrone, and prednimustine in relapsed patients","volume":"77","author":"Tirelli","year":"1996","journal-title":"Cancer"},{"issue":"5","key":"2020021109101813200_B24","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1097\/00042560-200112150-00002","article-title":"High-dose cytosine-arabinoside and cisplatin regimens as salvage therapy for refractory or relapsed AIDS-related non-Hodgkin\u2019s lymphoma","volume":"28","author":"Bi","year":"2001","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"15","key":"2020021109101813200_B25","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1182\/blood-2014-10-567479","article-title":"The biology and treatment of plasmablastic lymphoma","volume":"125","author":"Castillo","year":"2015","journal-title":"Blood"},{"issue":"19","key":"2020021109101813200_B26","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1200\/JCO.2005.07.084","article-title":"Prognostic factors and outcome of human herpesvirus 8-associated primary effusion lymphoma in patients with AIDS","volume":"23","author":"Boulanger","year":"2005","journal-title":"J Clin Oncol"},{"key":"2020021109101813200_B27","article-title":"Bortezomib plus EPOCH is effective as frontline treatment in patients with plasmablastic lymphoma [published online ahead of print 12 March 2018]","author":"Castillo","journal-title":"Br J Haematol"},{"issue":"2","key":"2020021109101813200_B28","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1365-2141.2011.08618.x","article-title":"Phase I study of bortezomib plus ICE (BICE) for the treatment of relapsed\/refractory Hodgkin lymphoma","volume":"154","author":"Fanale","year":"2011","journal-title":"Br J Haematol"}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/2\/24\/3618\/1554988\/advances022095.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/2\/24\/3618\/1554988\/advances022095.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T09:46:16Z","timestamp":1581414376000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/2\/24\/3618\/15983\/Safety-and-efficacy-of-an-oncolytic-viral-strategy"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,20]]},"references-count":28,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2018,12,26]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2018022095","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,20]]}}}