Delay in B-lymphocyte recovery and function following rituximab for EBV-associated lymphoproliferative disease early post-allogeneic hematopoietic SCT

Masjosthusmann, Katja; Ehlert, Karoline; Eing, Bodo R.; Roth, Jodie L.; Koehler, Gabriele; Juêrgens, H.; Fruehwald, Michael; Groll, Andreas H.

doi:10.1038/bmt.2008.385

Cited by 18 publications

(14 citation statements)

References 34 publications

(62 reference statements)

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“…To date, however, little is known about the biological and immunological consequences of the use of rituximab during the early immune reconstitution phase after HSCT in pediatric patients. Investigations of patients with lymphoma have shown depletion of mature B‐cells in association with hypogammaglobulinemia lasting longer than six months in a significant number of cases (20–23). In our experience, an adequate immune reconstitution after the use of rituximab early after allo‐HSCT can take years.…”

Section: Discussionmentioning

confidence: 99%

Incidence, kinetics, and risk factors of Epstein–Barr virus viremia in pediatric patients after allogeneic stem cell transplantation

Bordon¹,

Padalko²,

Benoît³

et al. 2012

Pediatric Transplantation

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After allogeneic hematopoietic stem-cell transplantation (allo-HSCT), EBV infections can be potentially dangerous and even life threatening. We evaluated the EBV viremia in 80 consecutive allo-HSCT with quantitative EBV-PCR every 2 weeks during the first 3 months and monthly thereafter until 1 yr after allo-HSCT or until death. We found a significantly more frequent viremia in patients who had in vivo T-cell depletion in which 23 out of 51 (45%) had EBV-PCR positivity. The EBV virus load was also significantly higher in the in vivo T-cell depleted group. Three patients developed clinical symptoms of EBV-PTLD and were treated with monoclonal anti-CD20 antibodies. No EBV- driven mortality was seen in this cohort. In our opinion EBV-PCR monitoring is mandatory after allo-HSCT. Most of the patients with EBV viremia had a good evolution after tapering the immune suppression, so this should be the first-line management of pediatric patients with EBV viremia. Monoclonal anti-CD20 antibodies should be reserved for those patients with early symptoms of EBV-PTLD.

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Section: Discussionmentioning

confidence: 99%

Incidence, kinetics, and risk factors of Epstein–Barr virus viremia in pediatric patients after allogeneic stem cell transplantation

Bordon¹,

Padalko²,

Benoît³

et al. 2012

Pediatric Transplantation

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“…Effectiveness of rituximab in preemptive intervention of EBV-DNA-emia is higher than its use in therapy of probable or proven EBV-PTLD [2]. The treatment should be managed however with caution, because of profound B-cell depletion and delay in B-lymphocyte recovery and function [8]. Other methods of preemptive strategy include use of EBV-specific cytotoxic T lymphocytes, mostly as a second line treatment, or reduction of immunosuppression, which is not possible in all cases [3, 5, 9, 10].…”

Section: Discussionmentioning

confidence: 99%

Strategy of pre-emptive management of Epstein-Barr virus post-transplant lymphoproliferative disorder after stem cell transplantation: results of European transplant centers survey

Gil¹,

Styczyński²,

Komarnicki³

2012

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Aim of the studyEpstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is a serious complication after stem cell transplantation (SCT) and the number of patients at risk is increasing over time. Available data do not reflect general practice of diagnosis and treatment of this complication.Material and methodsIn 2009 a survey on management of the pre-emptive strategy of EBV infection was done and results from 74 European transplant centers were registered and analyzed.ResultsRegular monitoring for EBV after SCT is done by most of the participating centers (73%). In 68% of them the monitoring is performed in all alloSCT patients, while in remaining centers it is done in high-risk patients only. Quantitative EBV-DNA is performed in 97% of centers, mainly in whole blood (78%) and usually repeated once a week (60.9%). The monitoring for EBV reactivation is performed for a period of 3 months (37%) to 6 months (30%) or adjusted to risk factors (20%). Rituximab as a pre-emptive therapy for EBV-PTLD is routinely administered in 80% of responding centers. The number of EBV-DNA copies as an indicator for pre-emptive therapy with rituximab varies between the centers.ConclusionsThe strategy of management of EBV infection exists in most of the responding centers. Different approaches regarding indications for preemptive therapy are seen between centers: rituximab is administered as pre-emptive therapy in most participating transplant centers.

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“…In children with high risk of EBV reactivation, the preemptive administration of rituximab pre-transplant may be an effective prophylactic option. Rituximab depletes EBV-infected B cells and may delay B cell recovery, thus allowing T-cell recovery [16, 17]. In our series PTLD developed in two out of 34 patients with reactivation.…”

Section: Discussionmentioning

confidence: 93%

“…The treatment strategy includes the reduction of immunosuppression, rituximab (anti CD-20 antibody) that is highly effective for EBV-associated PTLD, and/or infusion of EBV-specific cytotoxic T-cells [15, 16]. However, little is known about the immunological consequences of the therapy with both rituximab and EBV-specific cytotoxic T-cells in paediatric allogeneic HSCT [17, 18]. Viral infections, including most commonly CMV and EBV reactivation, affect both the clinical and immunological recovery following allogeneic HSCT.…”

Section: Introductionmentioning

confidence: 99%

Immune recovery and the risk of CMV/ EBV reactivation in children post allogeneic haematopoietic stem cell transplantation

Janeczko¹,

Mielcarek²,

Rybka³

et al. 2016

cejoi

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Immune reconstitution was studied prospectively in 86 children who underwent allogeneic haematopoietic stem cell transplantation (HSCT). We analysed the risk of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation in correlation with the kinetics of immune recovery and in relation to other potential risk factors that may influence the reactivation of these viruses including: diagnosis, type of HSCT, source of stem cells, type of conditioning, or the occurrence of graft-versus-host disease (GvHD). The absolute number of lymphocyte subpopulations in peripheral blood was evaluated in seven timepoints following HSCT. Significantly lower values of both CD3+ and CD3+CD8+ lymphocytes on day +14 and significantly higher values of both these subsets on day +168 post-transplant in patients with CMV reactivation were observed. Significantly lower values of CD3+CD4+ subpopulation were noted in patients with CMV reactivation on day +28 post allo-HSCT. Significantly lower lymphocyte values in the group with EBV reactivation comparing with the group without EBV reactivation were confirmed only in the case of pan-B lymphocytes (CD19+) subpopulation on day +21, +28, and +84 post allo-HSCT. We identified the impact of CMV reactivation on occurrence of the intestinal acute GvHD, which occurred more frequently in the group with CMV reactivation compared with patients without reactivation. Higher incidence of chronic GvHD was also observed in patients with CMV reactivation compared to the group without reactivation. EBV reactivation occurred more frequently in patients receiving transplants from matched unrelated donors, in particular after peripheral blood stem cell transplantation and while implementing antithymocyte globulin as GvHD prophylaxis.

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Delay in B-lymphocyte recovery and function following rituximab for EBV-associated lymphoproliferative disease early post-allogeneic hematopoietic SCT

Cited by 18 publications

References 34 publications

Incidence, kinetics, and risk factors of Epstein–Barr virus viremia in pediatric patients after allogeneic stem cell transplantation

Incidence, kinetics, and risk factors of Epstein–Barr virus viremia in pediatric patients after allogeneic stem cell transplantation

Strategy of pre-emptive management of Epstein-Barr virus post-transplant lymphoproliferative disorder after stem cell transplantation: results of European transplant centers survey

Immune recovery and the risk of CMV/ EBV reactivation in children post allogeneic haematopoietic stem cell transplantation

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