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Acute graft-versus-host-disease (aGVHD) is a major complication following hematopoietic cell transplantations (HCTs). We have shown that HCT recipients in whom either the donor or patient had inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) have a higher incidence of developing more severe aGVHD. Previous studies established that increased proinflammatory cytokines are associated with increased risk for aGVHD and nonrelapse mortality post-HCT. We hypothesized that HCT recipients with donor or recipient iciHHV-6 (iciHHV-6 pos HCT cases) will have higher cytokine levels compared with HCT recipients without iciHHV-6 (iciHHV-6 neg HCT controls). We identified 64 iciHHV-6 pos HCT cases with plasma from days 7, 14, and/or 21 post-HCT and before aGVHD onset in patients who developed aGVHD. We identified 64 iciHHV-6 neg HCT controls matched for aGVHD risk factors. We also identified 28 donors with iciHHV-6 and 56 matched donors without iciHHV-6. We measured plasma cytokine concentrations for IL-6, suppression of tumorigenicity 2, T cell immunoglobulin and mucin-domain containing 3, TNFα, soluble TNF receptor 1 (TNFRp55), and C-reactive protein (CRP). We used Mann-Whitney tests and repeated-measures models to compare cytokine levels. iciHHV-6 pos HCT cases had higher CRP levels on day 7 and day 21 and higher TNFRp55 levels on day 14 and day 21 compared with iciHHV-6 neg HCT controls. These findings were recapitulated in a repeated-measures model. The differences were most evident among patients who subsequently developed aGVHD grades 2 to 4. Additionally, iciHHV-6 pos HCT cases had earlier-onset aGVHD (median, 20 versus 27 days post-HCT; P = .02). There were no differences in cytokine levels among healthy donors with or without iciHHV-6. This study demonstrates that HCT recipients with iciHHV-6 have higher proinflammatory cytokines that may be associated with increased risk for aGVHD., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Cytomegalovirus (CMV) transmission via stem cells or marrow in CMV donor seropositive/recipient seronegative (D+/R-) hematopoietic cell transplantation (HCT) is surprisingly inefficient, and factors associated with transmission in these high-risk HCT recipients are unknown. In a retrospective cohort of D+/R- HCT recipients, cumulative incidence curve estimates were used to determine posttransplantation rates of CMV and multivariable Cox proportional models to assess risk factors associated with transmission. A total of 447 patients from 1995 to 2007 were eligible for enrollment. Overall, 85 of 447 (19.0%) acquired CMV at a median of 49 days (IQR 41-60) posttransplantation. CMV disease before day 100 occurred in 6 of 447 (1.3%) patients and in 7 of 447 (1.6%) after day 100. The donor graft, specifically the total nucleated cell count (adjusted hazard ratio [HR] 2.7; 95% confidence interval [CI], 1.4-4.7, P = .0002), was the only factor associated with CMV transmission in multivariable analyses. Notably, the source stem cells (marrow versus peripheral blood stem cell [PBSC]), screening method, and graft-versus-host disease (GVHD) were not associated with transmission. Thus, a highly cellular graft was the only identifiable risk factor associated with CMV transmission, suggesting that viral genomic content of the donor graft determines transmission efficiency in D+/R- HCT recipients., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Peripheral blood stem cell (PBSC) products contain more T cells and monocytes when compared with bone marrow (BM), leading to fewer bacterial and fungal infections. Cytomegelovirus (CMV) viral load and disease as well as CMV-specific immune reconstitution were compared in patients enrolled in a randomized trial comparing PSBC and BM transplantation. There was a higher rate of CMV infection and disease during the first 100 days after transplantation among PBSC recipients (any antigenemia/DNAemia: PBSC, 63% vs BM, 42%, P = .04; CMV disease: PBSC, 17% vs BM, 4%, P = .03). By 2 years, CMV disease rates were similar. The early increase in CMV events correlated temporarily with lower CMV-specific CD4(+) T helper and CD8(+) cytotoxic T lymphocyte function at 30 days after transplantation in PBSC recipients. By 3 months after transplantation and thereafter, CMV-specific immune responses were similar between BM and PBSC recipients. In conclusion, higher CMV infection and disease rates occurred in PBSC transplant recipients early after transplantation. These differences may be because of a transient delay in CMV-specific immune reconstitution following PBSC transplantation., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)