Kinetics of Double-Stranded DNA Viremia After Allogeneic Hematopoietic Cell Transplantation

Hill, Joshua A.; Mayer, Bryan T.; Xie, Hu; Leisenring, Wendy; Huang, Meei‐Li; Stevens-Ayers, Terry; Milano, Filippo; Delaney, Colleen; Jerome, Keith R.; Zerr, Danielle M.; Nichols, Garrett; Boeckh, Michael; Schiffer, Joshua T.

doi:10.1093/cid/cix804

Cited by 60 publications

(67 citation statements)

References 27 publications

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“…79,80 While CMV is the most common virus to cause clinical problems post transplant, concurrent infection with more than one double stranded DNA virus is common in a number of transplant settings, particularly following cord blood and T cell depleted transplant, and is associated with adverse outcomes such as increased overall mortality. 81 Reactivation of one or more viruses may reflect global cellular immune deficiency [81][82][83][84] or may stem from the fact that CMV infection itself results in contraction of the immune repertoire post transplant thus predisposing to other viral infections. 75,81 It is not possible to distinguish these possibilities using presently available information.…”

Section: Factors Influencing CMV Immunity Post Transplantmentioning

confidence: 99%

CMV-specific immune reconstitution following allogeneic stem cell transplantation

et al. 2016

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Cytomegalovirus (CMV) remains a major contributor to morbidity and mortality following allogeneic haemopoietic stem cell transplant (HSCT) despite widespread use of viraemia monitoring and preemptive antiviral therapy. Uncontrolled viral replication occurs primarily in the first 100 d post transplant but this high risk period can extend to many months if immune recovery is delayed. The re-establishment of a functional population of cellular effectors is essential for control of virus replication and depends on recipient and donor serostatus, the stem cell source, degree of HLA matching and post-transplant factors such as CMV antigen exposure, presence of GVHD and ongoing use of immune suppression. A number of immune monitoring assays exist but have not yet become widely accessible for routine clinical use. Vaccination, adoptive transfer of CMV specific T cells and a number of graft engineering processes are being evaluated to enhance of CMV specific immune recovery post HSCT.

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Section: Factors Influencing CMV Immunity Post Transplantmentioning

confidence: 99%

CMV-specific immune reconstitution following allogeneic stem cell transplantation

et al. 2016

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“…An important reason for a recent rise in risk is the more extensive use of T‐cell depletion, which results in prolonged lymphopenia, increasing the risk of viral infection or reactivation. As described with other double‐stranded DNA viruses, high adenoviral loads in blood are predictive of a poor clinical outcome . Single‐center studies have suggested that intense or disseminated adenovirus (AdV) infection following allo‐HCT is associated with poorer clinical outcomes and that AdV viremia is an independent risk factor for mortality …”

Section: Introductionmentioning

confidence: 98%

Current practices in the management of adenovirus infection in allogeneic hematopoietic stem cell transplant recipients in Europe: The AdVance study

González‐Vicent

Verna²,

Pochon³

et al. 2019

European J of Haematology

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ObjectiveAdenovirus (AdV) infections are potentially life‐threatening for allogeneic hematopoietic stem cell transplant (allo‐HCT) recipients. The AdVance study aimed to evaluate the incidence, management, and outcomes of AdV infections in European allo‐HCT recipients.MethodsAs part of the study, physician surveys were conducted to determine current AdV screening and treatment practices at their center.ResultsAll of the 28 respondents who treat pediatric patients reported routine AdV screening practices, with 93% screening all allo‐HCT recipients and others screening those with transplant‐related risk factors. Nearly all centers take a pre‐emptive approach to AdV treatment in both high‐ (89%) and low‐risk patients (75%). Among the 14 respondents who treat adult patients, 5 (36%) reported routine screening practices and few (21%) screen all allo‐HCT recipients unless risk factors are present. In adults, pre‐emptive AdV treatment is uncommon and quantitative AdV thresholds are rare. Typical treatment for all patients with symptomatic AdV infection is off‐label intravenous cidofovir.ConclusionsOur findings confirm that screening for AdV is more common in pediatric patients. Antiviral treatment is employed in both pediatric and adult patients, although adults are generally treated when AdV disease is diagnosed. The approach to AdV screening and treatment is risk‐based and consistent with clinical guidelines.

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“…This approach allows control of both extracellular and intracellular viral reservoirs, which is beneficial as high levels of CMV viraemia are known to correlate with worse outcomes and increased likelihood of recurrent CMV infection. 31,32 CMVIg rescue therapy was safe and well tolerated, and almost one-third of patients (10/35) could be treated on an outpatient basis.…”

Section: Discussionmentioning

confidence: 99%

The use of CMVIg rescue therapy in cardiothoracic transplantation: A single‐center experience over 6 years (2011‐2017)

Santhanakrishnan

Yonan

Callan

et al. 2019

Clinical Transplantation

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Cytomegalovirus (CMV) is the most important infectious agent in solid organ transplant recipients and has a major impact on morbidity and mortality. Most cases are well managed with antiviral agents, but CMV hyperimmune globulin (CMVIg) can be used alongside antiviral therapy for prophylaxis in high-risk thoracic organ recipients and to treat life-threatening CMV infection or disease. CMVIg may also improve antiviral host defences when genetic resistance to antivirals or unwanted side effects occur. In this single-center, retrospective study, we reviewed the CMVIg use to supplement antiviral therapy as a "rescue therapy" in cardiothoracic transplant recipients. These comprised 12 single lung, 11 double lung, and 12 heart transplant recipients. Patients received a median of 2 doses of CMVIg, most often in combination with ganciclovir or valganciclovir, and reduced immunosuppression. One week after rescue therapy was initiated, CMV DNA levels were significantly reduced, and after four weeks, CMV DNA was undetectable in 73% patients. Only one patient died as a result of CMV-related disease. No significant adverse effects were observed. We conclude that CMVIg rescue therapy is safe, well tolerated, and effective at controlling viral replication in cardiothoracic transplant recipients.

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Kinetics of Double-Stranded DNA Viremia After Allogeneic Hematopoietic Cell Transplantation

Abstract: Persistent high viral load dsDNA viremia episodes after allogeneic HCT predict mortality. Virus-specific kinetics can guide timing and thresholds for early intervention in studies of novel agents.

Cited by 60 publications

References 27 publications

CMV-specific immune reconstitution following allogeneic stem cell transplantation

CMV-specific immune reconstitution following allogeneic stem cell transplantation

Current practices in the management of adenovirus infection in allogeneic hematopoietic stem cell transplant recipients in Europe: The AdVance study

The use of CMVIg rescue therapy in cardiothoracic transplantation: A single‐center experience over 6 years (2011‐2017)

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