Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

Madon, E; Giaccone, Luisa; Festuccia, Moreno; Brunello, Lucia; Busca, Alessandro; Bruno, Benedetto

doi:10.1080/17474086.2016.1174571

Cited by 51 publications

(36 citation statements)

References 127 publications

(84 reference statements)

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“…Anti-viral drugs targeting CMV are commonly used for transplantation patients with clinical reactivation of CMV upon transplantation 42 . In these patients, the use of anti-viral drugs can reduce viral load 43 , but not much is known about the effect of anti-viral drugs on the differentiation of CMV-specific EM T cells. Whether anti-viral therapy can be used to reduce EM T-cell differentiation and improve heterologous immunity was recently experimentally assessed by Beswick et al .…”

Section: Measures To Counteract Cytomegalovirus-associated Perturbatimentioning

confidence: 99%

Cytomegalovirus infection and progressive differentiation of effector-memory T cells

et al. 2018

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Primary cytomegalovirus (CMV) infection leads to strong innate and adaptive immune responses against the virus, which prevents serious disease. However, CMV infection can cause serious morbidity and mortality in individuals who are immunocompromised. The adaptive immune response to CMV is characterized by large populations of effector-memory (EM) T cells that are maintained lifelong, a process termed memory inflation. Recent findings indicate that infection with CMV leads to continuous differentiation of CMV-specific EM-like T cells and that high-dose infection accelerates this progression. Whether measures that counteract CMV infection, such as anti-viral drugs, targeting of latently infected cells, adoptive transfer of CMV-specific T cells, and vaccination strategies, are able to impact the progressive differentiation of CMV-specific EM-like cells is discussed.

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Section: Measures To Counteract Cytomegalovirus-associated Perturbatimentioning

confidence: 99%

Cytomegalovirus infection and progressive differentiation of effector-memory T cells

et al. 2018

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“…Notably, clinical isolates of human CMV differ in their tropism for HC and bone marrow stromal cells (Apperley et al, 1989;Simmons et al, 1990), so that the pathomechanism of impaired hematopoiesis likely differs between virus variants/strains. Cellular immunotherapy based on transfer of CMV-specific CD8 + T cells (Riddell et al, 1992;Walter et al, 1995;Moss and Rickinson, 2005;Feuchtinger et al, 2010;Neuenhahn et al, 2017) is an option to avoid myelosuppressive side effects as well as renal toxicity of antiviral drugs (Maffini et al, 2016) and to prevent CMV disease in those HCT recipients who are infected with drug-resistant CMV variants (Pei et al, 2017;Chemaly et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus-Associated Inhibition of Hematopoiesis Is Preventable by Cytoimmunotherapy With Antiviral CD8 T Cells

Renzaho

Podlech

Kühnapfel

et al. 2020

Front. Cell. Infect. Microbiol.

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Reactivation of latent cytomegalovirus (CMV) in recipients of hematopoietic cell transplantation (HCT) not only results in severe organ manifestations, but can also cause "graft failure" resulting in bone marrow (BM) aplasia. This inhibition of hematopoietic stem and progenitor cell engraftment is a manifestation of CMV infection that is long known in clinical hematology as "myelosuppression." Previous studies in a murine model of sex-chromosome mismatched but otherwise syngeneic HCT and infection with murine CMV have shown that transplanted hematopoietic cells (HC) initially home to the BM stroma of recipients but then fail to further divide and differentiate. Data from this model were in line with the hypothesis that infection of stromal cells, which constitute "hematopoietic niches" where hematopoiesis takes place, causes a local deficiency in essential hematopoietins. Based on this understanding, one must postulate that preventing infection of stromal cells should restore the stroma's capacity to support hematopoiesis. Adoptively-transferred antiviral CD8 + T cells prevent lethal CMV disease by controlling viral spread and histopathology in vital organs, such as liver and lungs. It remained to be tested, however, if they can also prevent infection of the BM stroma and thus allow for successful HC engraftment. Here we demonstrate that antiviral CD8 + T cells control stromal infection. By tracking male donor-derived sry + HC in the BM of infected female sry − recipients, we show the CD8 + T cells allow for successful donor HC engraftment and thereby prevent CMV-associated BM aplasia. These data provide a further argument for cytoimmunotherapy of CMV infection after HCT.

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“…Lastly, whenever possible, reduction in immunosuppression therapy and enrollment in clinical trials should be considered in refractory cases. Detailed reviews of pharmacologic management of CMV disease have been published . Intravenous immunoglobulin (IVIG) or anti‐CMV immunoglobulin have been used to control viral infection following allo‐HSCT .…”

Section: Management Of Common Viral Infectionsmentioning

confidence: 99%

Viral infections after allogeneic hematopoietic stem cell transplant

2019

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Viral infections are common causes of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). In particular, allogeneic HSCT induces a profound immunocompromised state that may last up to 24 months post transplant, or longer in case of chronic graft vs host disease (GVHD). The common viruses affecting HSCT patients are HSV, VZV, CMV, EBV, adenovirus, HHV6, BKvirus and upper respiratory viruses such as influenza, parainfluenza, and RSV. These infections typically occur in three distinct phases: pre-engraftment, early postengraftment, and late postengraftment. This review will have two major sections, the first will discuss the epidemiology and natural history of different viral infections and second part will discuss preventive and therapeutic strategies among HSCT patients.

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Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

Cited by 51 publications

References 127 publications

Cytomegalovirus infection and progressive differentiation of effector-memory T cells

Cytomegalovirus infection and progressive differentiation of effector-memory T cells

Cytomegalovirus-Associated Inhibition of Hematopoiesis Is Preventable by Cytoimmunotherapy With Antiviral CD8 T Cells

Viral infections after allogeneic hematopoietic stem cell transplant

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