Herpes-Virus Immunity and Acute Graft-Versus-Host Disease

Gratama, Jan-Willem; Stijnen, Theo; Weiland, H. T.; Hekker, A. C.; Gast, Gijsbert C. de; Zwaan, F. E.; Weijers, Thijs; D'Amaro, J; The, T. H.; Vossen, Jaak M.

doi:10.1016/s0140-6736(87)92088-5

Cited by 67 publications

(24 citation statements)

References 22 publications

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“…35,36 HHV6 might be a factor in enhancing tissue damage by inflammatory responses, which is also suggested for other viruses. 2,3,37,38,40 In line with previous studies, we confirmed that HHV6 reactivation was associated with decreased EFS. [5][6][7]39 This is probably caused by the high incidence of aGVHD (up to 37% in this study) after HHV6 reactivation.…”

Section: Resultssupporting

confidence: 91%

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Human herpes virus 6 reactivation: important predictor for poor outcome after myeloablative, but not non-myeloablative allo-SCT

Pagter

Schuurman

Keukens

et al. 2013

Bone Marrow Transplant

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Hematopoietic SCT (HSCT) is often complicated by viral reactivations. In this retrospective cohort study (January 2004-August 2008, predictors for human herpes virus 6 (HHV6)-reactivation and associations between HHV6-reactivation and clinical outcomes after allogeneic HSCT were studied. HHV6 DNA load in plasma was monitored weekly by quantitative real-time PCR. Associations between the main end point HHV6-reactivation and other end points, that is, acute GVHD (aGVHD) and NRM were analyzed using Cox proportional hazard models. In total, 108 patients receiving either a myeloablative (MA; n ¼ 60) or non-myeloablative (NMA; n ¼ 48) conditioning regimen were included. Median age was 40 years (range 17-65); median follow-up was 20 months (range 3-36). In 16/60 (27%) patients with MA conditioning regimen, a HHV6 reactivation was observed (mean viral load 50 323 cp/mL) compared with 2/48 (4%) patients with a NMA conditioning regimen with low viral load (mean 1100 cp/mL). In multivariate analysis, MA conditioning was the only predictor for HHV6 reactivation (P ¼ 0.02). In addition, HHV6 reactivation was associated with grades 2-4 aGVHD (Po0.001) and NRM (P ¼ 0.03). Regular monitoring of HHV6 reactivation after HSCT might be important in MA HSCT patients to enable early initiation of antiviral treatment or to anticipate aGVHD, all of which may improve clinical outcome. Herpes virus reactivations, like human CMV (HCMV) and EBV, have been described to be associated with aGVHD, allograft rejections and increased NRM. 1-3 Human herpes virus 6 (HHV6), which reactivates early after HSCT, was found to be associated with aGVHD and increased NRM in children and, recently, in adults. [4][5][6][7] Predictors for the development of HHV6 reactivation are largely unknown. To date, only broad-spectrum and relatively toxic antiherpes virus drugs (for example, (val)ganciclovir and foscarnet-sodium) are used in the treatment of HHV6 disease or -reactivation. 8,9 With the progress in molecular diagnostics, better monitoring allows for further elucidation of the role of HHV6 reactivation and therapeutic protocols after HSCT. Therefore, we studied the predictors for HHV6 reactivation and the association of HHV6 reactivation with clinical outcome in adult allogeneic-HSCT recipients.

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Section: Resultssupporting

confidence: 91%

“…[1][2][3] Human herpes virus 6 (HHV6), which reactivates early after HSCT, was found to be associated with aGVHD and increased NRM in children and, recently, in adults. [4][5][6][7] Predictors for the development of HHV6 reactivation are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Human herpes virus 6 reactivation: important predictor for poor outcome after myeloablative, but not non-myeloablative allo-SCT

Pagter

Schuurman

Keukens

et al. 2013

Bone Marrow Transplant

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“…We have shown that various protocols of intensified GVHD prophylaxis interfere with the effects of pretransplant herpes virus serology on the occurrence of grades II-IV acute GVHD. With respect to HSV, we have inferred that HSV-specific memory T lymphocytes in the grafts are responsible for the effect [7]. This contention is supported by the observation of BostrOm et al [4] that strong donor mononuclear cell reactivity to HSV is associated with an increased frequency of grades II-III GVHD.…”

Section: Resultsmentioning

confidence: 60%

“…First, a multivariate analysis of the interaction between donor and recipient pretransplant herpes virus serology and acute GVHD was performed on all 262 patients. Competing nonvirological factors in the analysis were chosen on the basis of their significant role in previous analyses ( Table 2, upper panel) [5,7]. With respect to herpes virus serology, significant but opposite effects were observed for donor HSV serology (higher risk vs. lower risk, seropositive vs. seronegative; p = 0.03) and donor EBV serology (higher risk vs. lower risk, seronegative vs. seropositive; p = 0.01) ( Table 2, lower panel).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, herpes virus carrier status leads to the development of virus-specific humoral and cellular immunity, so Several studies of the effects of pretransplant herpes virus serology in allogeneic bone marrow transplant (BMT) recipients and their donors on the development of acute GVHD have been performed (Table 1). Two singlecenter studies [2,7] were followed by a retrospective multicenter study of data collected by the European Group for Bone Marrow Transplantation [3]. In all studies, the risk of grades II-IV GVHD increased proportionally with the number of herpes viruses carried.…”

Section: Introductionmentioning

confidence: 99%

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Intensification of GVHD prophylaxis interferes with the effects of pretransplant herpes virus serology on the occurrence of grades II–IV acute graft-versus-host disease

et al. 1992

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Summary. The effects of pretransplant herpes virus serology on the occurrence of grades II-IV acute graftversus-host disease (GVHD) were studied in 262 recipients and their HLA-identical family donors. In 131 recipients on standard GVHD prophylaxis (either methotrexate or cyclosporin A) significant effects were observed for donor HSV serology (seropositivity associated with increased risk for GVHD) and donor EBV serology (seronegativity associated with increased risk). However, these effects were nonsignificant in the other 131 recipients on intensified GVHD prophylaxis (i.e., methotrexate combined with cyclosporin A, in vivo anti-T-cell monoclonal antibodies, or various procedures to reduce the T-cell numbers in the transplants).

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