Characteristics of Epstein-Barr virus reactivation after allogeneic haematopoietic stem cell transplantation in patients with chronic active Epstein-Barr virus disease: favorable responses to rituximab.
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ABSTRACT:
SUBMITTER: Wei N
PROVIDER: S-EPMC8189911 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Characteristics of Epstein-Barr virus reactivation after allogeneic haematopoietic stem cell transplantation in patients with chronic active Epstein-Barr virus disease: favorable responses to rituximab.
Wei Na N Wang Yini Y Wang Jingshi J Wu Lin L Wang Zhao Z
Bone marrow transplantation 20210108 6
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Project description:Letermovir (LTV) prophylaxis is effective in reducing the incidence of clinically significant cytomegalovirus (CMV) infection (cs CMVi) after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Since our centre began administering LTV prophylaxis in June 2022, we have observed a certain increase in the incidence of Epstein-Barr virus (EBV) reactivation after haploidentical HSCT. We retrospectively analysed 230 consecutive patients who underwent haploidentical HSCT with rabbit anti-thymocyte globulin (ATG) from October 2022 to June 2023. The LTV group included 133 patients who received LTV prophylaxis, and the control group included 97 patients who did not receive LTV prophylaxis. At 1 year after HSCT, EBV reactivation was observed in 36 patients (27%) in the LTV group and 13 patients (13%) in the control group (p = 0.012). All patients with EBV reactivation had EBV-DNAemia, and one patient in each group developed EBV-associated posttransplantation lymphoproliferative disorder (PTLD). The proportion of patients with low EBV-DNA loads (> 5 × 102 to < 1 × 104 copies/mL) was greater in the LTV group than in the control group (23% vs. 10%, p = 0.01). The proportion of patients with CMV reactivation was lower in the LTV group than in the control group (35% vs. 56%, p = 0.002). There was no significant difference between the groups in terms of neutrophil and platelet count recovery, the cumulative incidence of acute/chronic graft-versus-host disease, overall survival, cumulative relapse rate or nonrelapse mortality. Our results show that the increased incidence of EBV reactivation may be associated with LTV prophylaxis for CMV after haploidentical HSCT.
| S-EPMC11470676 | biostudies-literature
Project description:Epstein-Barr virus (EBV) establishes a lifelong latent infection in healthy humans, kept under immune control by cytotoxic T cells (CTLs). Following paediatric haematopoetic stem cell transplantation (HSCT), a loss of immune surveillance leads to opportunistic outgrowth of EBV-infected cells, resulting in EBV reactivation, which can ultimately progress to post-transplant lymphoproliferative disorder (PTLD). The aims of this study were to identify risk factors for EBV reactivation in children in the first 100 days post-HSCT and to assess the suitability of a previously reported mathematical model to mechanistically model EBV reactivation kinetics in this cohort. Retrospective electronic data were collected from 56 children who underwent HSCT at Great Ormond Street Hospital (GOSH) between 2005 and 2016. Using EBV viral load (VL) measurements from weekly quantitative PCR (qPCR) monitoring post-HSCT, a multivariable Cox proportional hazards (Cox-PH) model was developed to assess time to first EBV reactivation event in the first 100 days post-HSCT. Sensitivity analysis of a previously reported mathematical model was performed to identify key parameters affecting EBV VL. Cox-PH modelling revealed EBV seropositivity of the HSCT recipient and administration of anti-thymocyte globulin (ATG) pre-HSCT to be significantly associated with an increased risk of EBV reactivation in the first 100 days post-HSCT (adjusted hazard ratio (AHR) = 2.32, P = 0.02; AHR = 2.55, P = 0.04). Five parameters were found to affect EBV VL in sensitivity analysis of the previously reported mathematical model. In conclusion, we have assessed the effect of multiple covariates on EBV reactivation in the first 100 days post-HSCT in children and have identified key parameters in a previously reported mechanistic mathematical model that affect EBV VL. Future work will aim to fit this model to patient EBV VLs, develop the model to account for interindividual variability and model the effect of clinically relevant covariates such as rituximab therapy and ATG on EBV VL.
| S-EPMC9314642 | biostudies-literature
Project description:Reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV) is common after hematopoietic stem cell transplantation (HSCT). Previous researches have demonstrated that either CMV or EBV reactivation is associated with poor outcomes of HSCT. However, few studies investigate the impact of CMV and EBV co-reactivation after HSCT. In this study, we described the clinical characteristics of HSCT recipients with CMV and EBV co-reactivation (defined as CMV and EBV viremia occur at the same period of time). We conducted a longitudinal study of 247 patients who underwent HSCT in our center. A total of 24 (9.7%) patients had CMV and EBV co-reactivation. These patients showed higher incidence of viral pneumonitis (P=0.005). Patients with CMV and EBV co-reactivation had significant lower 1-year overall survival (OS) (P=0.004) and lower 1-year leukemia free survival (LFS) (P=0.016). Our further analysis suggested that duration of CMV (P=0.014), EBV (P<0.001), and CD4+CD25+ T cell counts at day 30 post-transplantation (P=0.05) are independent risk factors of virus co-reactivation. In conclusion, patients who developed co-reactivation of CMV and EBV had poor prognosis in terms of lower 1-year OS and LFS, and the CMV and EBV co-reactivation was associated with prolonged CMV or EBV duration and poor CD4+CD25+ T cell reconstitution at day 30 post-transplantation.
| S-EPMC7921792 | biostudies-literature
Project description:Epstein Barr viremia (EBV) and posttransplantation lymphoproliferative disorder (PTLD) are complications of hematopoietic stem cell transplantation (HSCT). The use of antithymocyte globulin (ATG) in recipients of umbilical cord HSCT is a known risk factor for the development of PTLD. In this high-risk population, we implemented an EBV monitoring program with preemptive therapy with rituximab (375 mg/m(2) intravenously [i.v.]) for EBV viremia (>1000 copies/mL). Eight of 35 patients treated with a UCB HSCT between 2007 and 2009, developed EBV viremia. Two of 7 developed PTLD (with 1 of the 2 dying of PTLD), despite prophylactic rituximab use. When compared with our previously described cohort where 6 of 30 developed EBV viremia and 5 of 6 patients developed PTLD (with 2 of 5 dying of PTLD), the incidence of PTLD appears to be less when prophylactic rituximab is administered. Despite small numbers, our observations suggest that in this high-risk population, EBV monitoring accompanied by preemptive therapy may reduce the risk of progression to life-threatening PTLD; further follow-up of this cohort and a larger multi-institutional prospective study of this preemptive strategy is warranted.
| S-EPMC4113553 | biostudies-literature
Project description: Not available
| S-EPMC10671524 | biostudies-literature
Project description:The co-reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients undergoing hematopoietic stem cell transplantation (HSCT) has been found. Research has shown that the reactivation of CMV or EBV is closely related to poor HSCT outcomes. In this study, we describe the clinical characteristics of HSCT patients with co-reactivation of CMV and EBV. We retrospectively reviewed the medical records of 327 patients who underwent HSCT at the Peking University People's Hospital Institute of Hematology. Co-reactivation of CMV and EBV was observed in a total of 75 patients (22.9%) who also had a higher incidence of hemorrhagic cystitis (P=0.000). HSCT patients with CMV and co-reactivation of CMV and EBV had a significantly lower 1-year overall survival (OS; P=0.050). Further, COX regression analysis showed that viral infection was a risk factor for 1-year OS (HR, 12.625 for co-reactivation vs. no reactivation, p=0.021, and HR 13.580 for CMV reactivation vs. no reactivation, P=0.013). In conclusion, the patients with CMV reactivation had poorer outcome after HSCT regardless of EBV reactivation.
| S-EPMC8992791 | biostudies-literature
Project description:ImportanceAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the only effective treatment for chronic active Epstein-Barr virus infection (CAEBV). The clinical efficacy and safety of allo-HSCT with different conditioning regimens in children with CAEBV remain unclear.ObjectiveTo evaluate the effectiveness and safety of allo-HSCT with the modified myeloablative conditioning (MAC) regimen for children with CAEBV and also the factors affecting the outcomes.MethodsWe retrospectively analyzed children with CAEBV who underwent allo-HSCT with the modified MAC regimen at Beijing Children's Hospital, Capital Medical University from October 2016 to June 2021. Data related to the clinical manifestations, engraftment, and outcome were extracted from the medical records.ResultsThe cohort comprised 41 patients (24 males, 17 females) with a median transplantation age of 92.6 (60.4, 120.7) months and a median follow-up time of 28.2 (15.3, 40.2) months. Four patients (9.8%) died, among which three died from primary disease relapse, and one died from grade IV acute graft-versus-host diseases (aGVHD) after stopping treatment. The 3-year overall survival (OS) and 3-year event-free survival (EFS) rates were 88.8% ± 5.4% and 85.0% ± 5.7%, respectively. The 3-year OS and EFS did not significantly differ between the patients with hemophagocytic lymphohistiocytosis (HLH) and the patient without HLH (87.7% ± 6.8% vs. 91.7% ± 8.0%, P = 0.790; 85.0% ± 6.9% vs. 84.6% ± 10.0%, P = 0.921), or among the patients with complete remission, partial remission, and activity disease before HSCT (all P > 0.05). Multivariate analysis showed that grade III-IV aGVHD was a risk factor for mortality (Hazards ratio: 11.65, 95% confidence interval: 1.00, 136.06; P = 0.050).InterpretationAllo-HSCT with the modified MAC regimen is safe and effective for pediatric CAEBV. This treatment benefits patients with HLH or active disease. Patients with Grade III-IV aGVHD may be associated with worse outcomes.
| S-EPMC9789936 | biostudies-literature
Project description: Not available
| S-EPMC7609913 | biostudies-literature
Project description: Not available
| S-EPMC10699715 | biostudies-literature
Project description:Epstein-Barr virus (EBV) infects more than 90% of the human population worldwide and establishes lifelong infection in hosts by switching between latent and lytic infection. EBV latency can be reactivated under appropriate conditions, leading to expression of the viral lytic genes and production of infectious progeny viruses. EBV reactivation involves crosstalk between various factors and signaling pathways, and the subsequent complicated virus-host interplays determine whether EBV continues to propagate. However, the detailed mechanisms underlying these processes remain unclear. In this review, we summarize the critical factors regulating EBV reactivation and the associated mechanisms. This encompasses the transcription and post-transcriptional regulation of immediate-early (IE) genes, the functions of viral factors on viral DNA replication and progeny virus production, the mechanisms through which viral proteins disrupt and inhibit the host's innate immune response, and the host factors that modulate EBV reactivation. Finally, we explore the potential applications of novel technologies in studying EBV reactivation, providing novel insights into the investigation of mechanisms governing EBV reactivation and the development of anti-EBV therapeutic strategies.
| S-EPMC11655498 | biostudies-literature