http://repub.eur.nl/res/aut/5477/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39055/ 2012-08-01T00:00:00Z EBV seronegative recipients of cardiac transplantation are at risk for development of post transplant lymphoproliferative disease following primary EBV infection due to the ongoing treatment with immunosuppressive drugs. Here we present detailed kinetics of the EBV-specific T-cell response following cardiac transplantation in an EBV seronegative recipient who developed a primary EBV infection 15weeks post transplantation and subsequent viral reactivations throughout follow up. The patient developed an EBV-specific CD8+T-cell response within 24days after first detection of the primary infection. Subsequently, an increased EBV-specific CD8+T-cell response developed upon viral reactivation, indicated by a threefold increase of EBV-specific CD8+T cells and increased IFNy production after stimulation with EBV-specific peptide pools. These data indicate that an EBV-specific T-cell response capable of adequate control of a primary EBV-infection and subsequent viral reactivations can develop in an EBV seronegative cardiac transplant recipient in the presence of severe immunosuppression. http://repub.eur.nl/res/pub/19476/ 2010-03-01T00:00:00Z Background. Epstein-Barr virus (EBV) and cytomegalovirus reactivations are frequent complications of hematopoeitic allogeneic stem cell transplantation (SCT) because of a lack of T cell control after immunosuppression. Early diagnosis of reactivation and subsequent preemptive therapy relies on frequent viral load measurement. Additional virus-specific T cell reconstitution data could improve the predictive value of viral load detection for viral complications after transplantation. Here, we studied perforin expression in CD8+ T cells as a measure of cytotoxic T cell capacity in relation to the occurrence of viral reactivation. Methods. In a prospective study, we monitored 40 patients during the first 3 months after transplantation and measured viral loads in combination with intracellular perforin expression in CD8+ T cells. Results. Median perforin expression in CD8+ T cells throughout follow-up was higher in patients with viral reactivations than in patients without viral reactivations (4.9% vs 2.3%; P = .001). The median percentage of perforin-expressing CD8+ T cells in patients with high viral reactivations exceeding 1000 copies/mL (10.7%) was statistically significantly higher than that in patients with minor reactivations of 50-1000 copies (4.0%), that in patients with detectable EBV loads that did not exceed the detection limit of 50 copies/mL (2.9%), and that in patients without reactivations (0.8%). Patients with high viral reactivations reached a high percentage of perforinexpressing CD8+ T cells (>10.2%) more often and faster than did patients with low viral loads (≤1000 copies/mL) or without viral reactivations. High perforin expression preceded high viral loads. Conclusion. Perforin-expressing CD8+ T cells may be useful as an easy-to-measure prognostic marker for identifying patients at risk for severe viral reactivation very soon after SCT. http://repub.eur.nl/res/pub/16739/ 2009-10-26T00:00:00Z A prospective subgroup analysis of two prospective, randomized, double-blind, placebo-controlled phase III clinical trials showed that the combination of lenalidomide plus dexamethasone is superior to dexamethasone alone in patients with relapsed or refractory multiple myeloma who had been previously treated with thalidomide; the implications for clinical practice are discussed. http://repub.eur.nl/res/pub/30238/ 2008-12-01T00:00:00Z Human herpesvirus type 6 (HHV6) is known to reactivate after hematopoetic stem cell transplantation (HSCT) and has been suggested to be associated with increased mortality and severe clinical manifestations, including graft versus host disease (GvHD). The exact etiological role of HHV6 reactivation in increased morbidity and mortality after HSCT remains unclear. This review will focus on the current available evidence of HHV6 reactivation after HSCT and its immuno-modulatory capacities, with particular emphasis on the severe complication GvHD. At present, no effective specific antiviral treatment for HHV6 reactivation has been identified. The currently available antiviral agents are outlined, as well as possible future strategies for the treatment of HHV6 reactivation. Non-toxic, specific treatment or prevention of HHV6 reactivation might improve the safety and efficacy of the HSCT procedure. http://repub.eur.nl/res/pub/14420/ 2008-11-01T00:00:00Z EBV DNA levels should be monitored in patients with high-risk features. Early treatment may be instituted at predefined DNA levels (preemptive approach) or at the earliest signs of LPD (prompt approach). Stepwise treatment guided by EBV DNA, including interruption of immunosuppression, rituximab, and adoptive T-cell immunotherapy may all add to the low mortality currently associated with LPD following allogeneic stem cell transplantation. http://repub.eur.nl/res/pub/28938/ 2008-08-01T00:00:00Z Allogeneic hematopoietic stem cell transplantation (alloSCT) has been established as a powerful treatment modality in acute myeloid leukemia (AML) in first or subsequent remission. Although alloSCT effectively prevents relapse, non-relapse mortality (NRM) associated with the procedure may counterbalance that beneficial effect. As a result, alloSCT generally is restricted to patients with a relatively high risk of relapse and a relatively low risk for NRM. Here, we review recent studies that evaluated specific risk factors that, on the one hand, identified categories of AML patients with a higher risk of relapse and, on the other hand, identified patients with an increased risk for NRM. We discuss how these recent developments may affect our decision-making about whether and when to proceed to alloSCT. http://repub.eur.nl/res/pub/30181/ 2008-07-01T00:00:00Z Chronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. These 2 abnormal Epstein-Barr virus-associated diseases are seldom reported in individuals other than Japanese children and adolescents. We report a series of 2 adult non-Japanese patients with fatal chronic active Epstein-Barr virus and 1 adult non-Japanese patient with Epstein-Barr virus hemophagocytic lymphohistiocytosis and discuss its pathogenesis and treatment options. http://repub.eur.nl/res/pub/8169/ 2002-01-01T00:00:00Z Recipients of a partially T-cell-depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV-lymphoproliferative disease (EBV-LPD). We studied whether preemptive therapy with rituximab prevents EBV-LPD, LPD-mortality, and abrogates viral reactivation in high-risk patients. We monitored 49 recipients of a TCD allo-SCT weekly for EBV reactivation by quantitative real-time polymerase chain reaction (PCR). Preemptive therapy by a single infusion of rituximab was given to patients with viral reactivation more than or equal to 1000 geq/mL. Results were compared with an historical control group of patients retrospectively monitored for EBV reactivation at similar intervals. There were 17 prospectively monitored patients who showed EBV reactivation more than or equal to 1000 geq/mL and 15 received preemptive therapy. Median time to preemptive therapy was 113 days (range, 41-202 days) after SCT. There were 14 patients who showed complete response (CR) as characterized by prevention of EBV-LPD and complete clearance of EBV-DNA from plasma, which was achieved after a median number of 8 days (range, 1-46 days). One patient progressed to EBV-LPD despite preemptive therapy, but obtained CR after 2 infusions of rituximab and donor lymphocyte infusion. There were 2 patients who had already developed EBV-LPD prior to preemptive rituximab, but obtained CR following 2 rituximab infusions. Comparison of this prospectively followed series to our historical cohort with the same high-risk profile showed a reduction of EBV-LPD incidence (18% +/- 9% versus 49% +/- 11%, respectively) and a complete abrogation of LPD-mortality (0% versus 26% +/- 10%, respectively) (P =.04) at 6 months from EBV-DNA more than or equal to 1000 geq/mL. Frequent quantitative monitoring of EBV reactivation and preemptive therapy by rituximab improves outcome in patients at high risk of EBV-LPD. http://repub.eur.nl/res/pub/8246/ 2001-01-01T00:00:00Z Reactivation of the Epstein-Barr virus (EBV) after allogeneic stem cell transplantation (allo-SCT) may evoke a protective cellular immune response or may be complicated by the development of EBV-lymphoproliferative disease (EBV-LPD). So far, very little is known about the incidence, recurrence, and sequelae of EBV reactivation following allo-SCT. EBV reactivation was retrospectively monitored in 85 EBV-seropositive recipients of a T-cell--depleted (TCD) allo-SCT and 65 EBV-seropositive recipients of an unmanipulated allo-SCT. Viral reactivation (more than 50 EBV genome equivalents [gEq]/mL) was monitored frequently by quantitative real-time plasma polymerase chain reaction until day 180 after SCT. Probabilities of developing viral reactivation were high after both unmanipulated and TCD-allogeneic SCT (31% +/- 6% versus 65% +/- 7%, respectively). A high CD34(+) cell number of the graft appeared as a novel significant predictor (P =.001) for EBV reactivation. Recurrent reactivation was observed more frequently in recipients of a TCD graft, and EBV-LPD occurred only after TCD-SCT. High-risk status, TCD, and use of antithymocyte globulin were predictive for developing EBV-LPD. Plasma EBV DNA quantitatively predicted EBV-LPD. The positive and negative predictive values of a viral load of 1000 gEq/mL were, respectively, 39% and 100% after TCD. Treatment-related mortality did not differ significantly between TCD and non-TCD transplants, but the incidence of chronic graft-versus-host disease was significantly less in TCD patients. It is concluded that EBV reactivation occurs frequently after TCD and unmanipulated allo-SCT, especially in recipients of grafts with high CD34(+) cell counts. EBV-LPD, however, occurred only after TCD, and EBV load quantitatively predicted EBV-LPD in recipients of a TCD graft. (Blood. 2001;98:972-978)