The Experts below are selected from a list of 14976 Experts worldwide ranked by ideXlab platform
Borko Jovanovic - One of the best experts on this subject based on the ideXlab platform.
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multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
Journal of Clinical Oncology, 2010Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko JovanovicAbstract:Purpose Adult post-transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. Methods We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) –related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) ...
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multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
Journal of Clinical Oncology, 2010Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko JovanovicAbstract:PURPOSE Adult post-transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. METHODS We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) -related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P or = 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11%, respectively (P < .0001). CONCLUSION This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.
Shannon C Kenney - One of the best experts on this subject based on the ideXlab platform.
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leflunomide teriflunomide inhibit epstein barr virus ebv induced Lymphoproliferative Disease and lytic viral replication
Oncotarget, 2017Co-Authors: Andrea Bilger, Henri Jacques Delecluse, Julie Plowshay, Dhananjay M Nawandar, Elizabeth A Barlow, James C Romeromasters, Jillian A Bristol, Ming Han Tsai, Shannon C KenneyAbstract:// Andrea Bilger 1 , Julie Plowshay 2, 6 , Shidong Ma 1, 5 , Dhananjay Nawandar 3, 7 , Elizabeth A. Barlow 1 , James C. Romero-Masters 4 , Jillian A. Bristol 1 , Zhe Li 8 , Ming-Han Tsai 8 , Henri-Jacques Delecluse 8 and Shannon C. Kenney 1, 2 1 Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA 2 Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA 3 Department Cellular and Molecular Biology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, USA 4 Department of Cellular and Molecular Pathology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA 5 Sanofi Pharmaceuticals, Cambridge, Massachusetts, USA 6 Rocky Mountain Infectious Disease Specialists, Aurora, Colorado, USA 7 Department of Cancer Biology and Immunology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Cambridge, Massachusetts, USA 8 Joint DKFZ Inserm Unit U1074, German Cancer Center (DKFZ), Heidelberg, Germany Correspondence to: Shannon C. Kenney, email: skenney@wisc.edu Keywords: therapy, lymphoma, Lymphoproliferative Disease, humanized mouse model, FDA-approved Received: March 17, 2017 Accepted: April 27, 2017 Published: May 15, 2017 ABSTRACT EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced Lymphoproliferative Disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both “on target” and “off target” mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.
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epstein barr virus lytic infection contributes to Lymphoproliferative Disease in a scid mouse model
Journal of Virology, 2005Co-Authors: Gregory K Hong, Margaret L Gulley, Wen Hai Feng, Henri Jacques Delecluse, Elizabeth Holleyguthrie, Shannon C KenneyAbstract:Most Epstein-Barr virus (EBV)-positive tumor cells contain one of the latent forms of viral infection. The role of lytic viral gene expression in EBV-associated malignancies is unknown. Here we show that EBV mutants that cannot undergo lytic viral replication are defective in promoting EBV-mediated Lymphoproliferative Disease (LPD). Early-passage lymphoblastoid cell lines (LCLs) derived from EBV mutants with a deletion of either viral immediate-early gene grew similarly to wild-type (WT) virus LCLs in vitro but were deficient in producing LPD when inoculated into SCID mice. Restoration of lytic EBV gene expression enhanced growth in SCID mice. Acyclovir, which prevents lytic viral replication but not expression of early lytic viral genes, did not inhibit the growth of WT LCLs in SCID mice. Early-passage LCLs derived from the lytic-defective viruses had substantially decreased expression of the cytokine interleukin-6 (IL-6), and restoration of lytic gene expression reversed this defect. Expression of cellular IL-10 and viral IL-10 was also diminished in lytic-defective LCLs. These results suggest that lytic EBV gene expression contributes to EBV-associated Lymphoproliferative Disease, potentially through induction of paracrine B-cell growth factors.
Umaimainthan Palendira - One of the best experts on this subject based on the ideXlab platform.
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Cerebral Vasculitis in X-linked Lymphoproliferative Disease Cured by Matched Unrelated Cord Blood Transplant
Journal of clinical immunology, 2015Co-Authors: Paul A. Gray, Umaimainthan Palendira, Tracey A. O'brien, Mayura Wagle, Stuart G. Tangye, Tony Roscioli, Sharon Choo, Rosemary Sutton, John B. Ziegler, Katie FrithAbstract:ᅟ Vasculitis occurs rarely in association with X-linked Lymphoproliferative Disease (XLP). There are four published cases of non-EBV XLP-associated cerebral vasculitis reported, none of whom have survived without major cognitive impairment.
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expansion of somatically reverted memory cd8 t cells in patients with x linked Lymphoproliferative Disease caused by selective pressure from epstein barr virus
Journal of Experimental Medicine, 2012Co-Authors: Umaimainthan Palendira, Carol Low, Andrew I Bell, Cindy S, Rachel Abbott, Tri Giang Phan, Sean D RimintonAbstract:Patients with the primary immunodeficiency X-linked Lymphoproliferative Disease (XLP), which is caused by mutations in SH2D1A, are highly susceptible to Epstein-Barr virus (EBV) infection. Nonetheless, some XLP patients demonstrate less severe clinical manifestations after primary infection. SH2D1A encodes the adaptor molecule SLAM-associated protein (SAP), which is expressed in T and natural killer cells and is required for cytotoxicity against B cells, the reservoir for EBV. It is not known why the clinical presentation of XLP is so variable. In this study, we report for the first time the occurrence of somatic reversion in XLP. Reverted SAP-expressing cells resided exclusively within the CD8(+) T cell subset, displayed a CD45RA(-)CCR7(-) effector memory phenotype, and were maintained at a stable level over time. Importantly, revertant CD8(+) SAP(+) T cells, but not SAP(-) cells, proliferated in response to EBV and killed EBV-infected B cells. As somatic reversion correlated with EBV infection, we propose that the virus exerts a selective pressure on the reverted cells, resulting in their expansion in vivo and host protection against ongoing infection.
Dixon B Kaufman - One of the best experts on this subject based on the ideXlab platform.
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multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
Journal of Clinical Oncology, 2010Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko JovanovicAbstract:Purpose Adult post-transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. Methods We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) –related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P < .0001) ...
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multicenter analysis of 80 solid organ transplantation recipients with post transplantation Lymphoproliferative Disease outcomes and prognostic factors in the modern era
Journal of Clinical Oncology, 2010Co-Authors: Andrew M Evens, Kevin A David, Irene Helenowski, Beverly P Nelson, Dixon B Kaufman, Sheetal Mehta Kircher, Alla Gimelfarb, Elise Hattersley, Lauren Mauro, Borko JovanovicAbstract:PURPOSE Adult post-transplantation Lymphoproliferative Disease (PTLD) has a reported 3-year overall survival (OS) of 35% to 40%. The impact of rituximab on the outcome of PTLD is not well defined. METHODS We examined the clinical features and outcomes among a large cohort of solid organ transplantation (SOT) -related patients with PTLD who were recently treated at four Chicago institutions (from January 1998 to January 2008). Results Eighty patients with PTLD were identified who had a median SOT-to-PTLD time of 48 months (range, 1 to 216 months). All patients had reduction of immunosuppression as part of initial therapy, whereas 59 (74%) of 80 patients received concurrent first-line rituximab with or without chemotherapy. During 40-month median follow-up, 3-year progression-free survival (PFS) for all patients was 57%, and the 3-year overall survival (OS) rate was 62%. Patients who received rituximab-based therapy as part of initial treatment had 3-year PFS of 70% and OS 73% compared with 21% (P or = 2) was formed: 3-year PFS rates were 84%, 66%, 7%, respectively, and 3-year OS rates were 93%, 68%, 11%, respectively (P < .0001). CONCLUSION This large, multicenter, retrospective analysis suggests significantly improved PFS and OS associated with early rituximab-based treatment in PTLD. In addition, clinical factors at diagnosis identified patients with markedly divergent outcomes.
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dissociation of depletional induction and posttransplant Lymphoproliferative Disease in kidney recipients treated with alemtuzumab
American Journal of Transplantation, 2007Co-Authors: Allan D Kirk, Dixon B Kaufman, Vikas R Dharnidharka, Wida S Cherikh, M Ring, George W Burke, Stuart J Knechtle, Santosh Potdar, R Shapiro, H M KauffmanAbstract:Transplant patients are at the risk for posttransplant Lymphoproliferative Disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk.
Markus Maeurer - One of the best experts on this subject based on the ideXlab platform.
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risk factors for epstein barr virus related post transplant Lymphoproliferative Disease after allogeneic hematopoietic stem cell transplantation
Haematologica, 2014Co-Authors: Michael Uhlin, Helena Wikell, Mikael Sundin, Ola Blennow, Markus MaeurerAbstract:Allogeneic hematopoietic stem cell transplantation is a successful treatment for hematologic malignancies and a variety of genetic and metabolic disorders. In the period following stem cell transplantation, the immune-compromised milieu allows opportunistic pathogens to thrive. Epstein-Barr virus-associated post-transplant Lymphoproliferative Disease can be a life-threatening complication for transplanted patients because of suppressed T-cell-mediated immunity. We analyzed possible risk factors associated with post-transplant Lymphoproliferative Disease in a cohort of over 1,000 patients. The incidence of post-transplant Lymphoproliferative Disease was 4%. Significant risk factors identified by multivariate analysis were: human leukocyte antigen-mismatch ( P <0.001), serological Epstein-Barr virus mismatch recipient−/donor+ ( P <0.001), use of reduced intensity conditioning ( P =0.002), acute graft- versus -host Disease grade II to IV ( P =0.006), pre-transplant splenectomy ( P =0.008) and infusion of mesenchymal stromal cells ( P =0.015). The risk of post-transplant Lymphoproliferative Disease has increased in more recent years, from less than 2% before 1998 to more than 6% after 2011. Additionally, we show that long-term survival of patients with post-transplant Lymphoproliferative Disease is poor despite initial successful treatment. The 3-year survival rate among the 40 patients with post-transplant Lymphoproliferative Disease was 20% as opposed to 62% among patients without post-transplant Lymphoproliferative Disease ( P <0.001). The study identifies patients at risk of post-transplant Lymphoproliferative Disease after transplantation in need of pre-emptive measures.
