Preemptive Therapy Versus Valgancyclovir Prophylaxis in Cytomegalovirus-positive Kidney Transplant Recipients Receiving Antithymocyte Globulin Induction

Couzi, Lionel; Helou, S.; Bachelet, Thomas; Martin, S.; Moreau, Karine; Morel, D.; Lafon, Marie‐Edith; Garrigue, Isabelle; Merville, Pierre

doi:10.1016/j.transproceed.2012.09.029

Cited by 17 publications

(12 citation statements)

References 50 publications

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“…Surveillance and preemptive therapy is the widely used strategy for preventing CMV disease in both KT [3] and HCT [4], because universal prophylaxis appears to be associated with higher cost, adverse effects and late CMV infection [1,6,7,20,21]. However, some KT [6-8] and HCT [9] patients on preemptive therapy suffer from CMV disease.…”

Section: Discussionmentioning

confidence: 99%

Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy

Kim

Lee

et al. 2016

Korean J Intern Med

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Background/Aims:Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy.Methods:We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period.Results:The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001).Conclusions:The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.

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Section: Discussionmentioning

confidence: 99%

Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy

Kim

Lee

et al. 2016

Korean J Intern Med

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“…Despite effective anti-viral therapies, CMV is still associated with CMV infection or disease in immunocompromised kidney transplant recipients ( 4 , 5 ). CMV infection is characterized by CMV DNAemia (CMV DNA in blood or plasma, also called CMV viremia) regardless of symptoms and occurs in about 50% of CMV-seropositive patients (R+, patients with peripheral blood CMV IgG) ( 6 – 10 ), and up to 70% of donor-positive, seronegative-recipients (D+R−) in the absence of anti-viral prophylaxis ( 11 – 18 ). CMV disease can be a viral syndrome (CMV DNAemia with fever, malaise, leukopenia, and/or thrombocytopenia) or a tissue-invasive disease (where CMV is detected in the injured organs, mostly lungs, liver and intestines) ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

Direct and Indirect Effects of Cytomegalovirus-Induced Î³Î´ T Cells after Kidney Transplantation

et al. 2015

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Despite effective anti-viral therapies, cytomegalovirus (CMV) is still associated with direct (CMV disease) and indirect effects (rejection and poor graft survival) in kidney transplant recipients. Recently, an unconventional T cell population (collectively designated as Vδ2neg γδ T cells) has been characterized during the anti-CMV immune response in all solid-organ and bone-marrow transplant recipients, neonates, and healthy people. These CMV-induced Vδ2neg γδ T cells undergo a dramatic and stable expansion after CMV infection, in a conventional “adaptive” manner. Similarly, as CMV-specific CD8+ αβ T cells, they exhibit an effector/memory TEMRA phenotype and cytotoxic effector functions. Activation of Vδ2neg γδ T cells by CMV-infected cells involves the γδ T cell receptor (TCR) and still ill-defined co-stimulatory molecules such as LFA-1. A multiple of Vδ2neg γδ TCR ligands are apparently recognized on CMV-infected cells, the first one identified being the major histocompatibility complex-related molecule endothelial protein C receptor. A singularity of CMV-induced Vδ2neg γδ T cells is to acquire CD16 expression and to exert an antibody-dependent cell-mediated inhibition on CMV replication, which is controlled by a specific cytokine microenvironment. Beyond the well-demonstrated direct anti-CMV effect of Vδ2neg γδ T cells, unexpected indirect effects of these cells have been also observed in the context of kidney transplantation. CMV-induced Vδ2neg γδ T cells have been involved in surveillance of malignancy subsequent to long-term immunosuppression. Moreover, CMV-induced CD16+ γδ T cells are cell effectors of antibody-mediated rejection of kidney transplants, and represent a new physiopathological contribution to the well-known association between CMV infection and poor graft survival. All these basic and clinical studies paved the road to the development of a future γδ T cell-based immunotherapy. In the meantime, γδ T cell monitoring should prove a valuable immunological biomarker in the management of CMV infection.

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“…Five studies were open‐label RCTs . Of the observational studies, five had a retrospective cohort design and one a prospective cohort design . Four RCTs and one observational study included both CMV‐seropositive and ‐seronegative recipients, while the others restricted the study populations to only seropositive recipients.…”

Section: Resultsmentioning

confidence: 99%

Comparison of universal prophylaxis and preemptive approach for cytomegalovirus associated outcome measures in renal transplant patients: A meta‐analysis of available data

Çaşkurlu

Karadağ

Arslan

et al. 2018

Transplant Infectious Dis

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Cytomegalovirus (CMV) is a ubiquitous latent human virus that often causes complications in renal transplantation recipients. Universal prophylaxis and preemptive therapy are alternative strategies to prevent CMV associated complications. This meta‐analysis aimed to assess available data comparing the effectiveness of prophylaxis and preemptive therapy for preventing adverse outcomes. We searched the PubMed, Ovid, Web of Science, Cochrane Library, and Open Grey databases using a combination of keywords. Random effects models along with the Paule‐Mandel estimator were used to synthesize pooled effect estimates. Eleven studies were eligible for the final analysis. Universal prophylaxis was better at preventing CMV disease than the preemptive approach (risk difference = −0.0459; confidence intervals = −0.0791, −0.0127; P‐value = 0.0067; number needed to treat [NNT] = 22 [1/0.0459]; high, 79 [1/0.0127] patients; low, 13 [1/0.0791] patients). Subgroup analysis revealed a more consistent effect among studies published after 2010, with negligible between‐study heterogeneity. The NNT for universal prophylaxis to prevent one excess CMV disease concerning preemptive therapy was 16 (1/0.0630) patients (high, 25 [1/0.0394]; low, 12 [1/0.0867] patients) in the subgroup of studies performed after 2010. We detected no significant difference between the two strategies regarding acute rejection and graft loss, with negligible variability due to heterogeneity between studies. Although universal prophylaxis performed better than the preemptive strategy for the prevention of CMV disease, the high NNT value may discourage the use of CMV prophylaxis. Since there were no differences between the strategies concerning acute rejection and graft loss, this study supports the use of the preemptive approach as an alternative to universal prophylaxis.

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Preemptive Therapy Versus Valgancyclovir Prophylaxis in Cytomegalovirus-positive Kidney Transplant Recipients Receiving Antithymocyte Globulin Induction

Cited by 17 publications

References 50 publications

Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy

Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy

Direct and Indirect Effects of Cytomegalovirus-Induced Î³Î´ T Cells after Kidney Transplantation

Comparison of universal prophylaxis and preemptive approach for cytomegalovirus associated outcome measures in renal transplant patients: A meta‐analysis of available data

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