Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials: Table 1.

Ljungman, Per; Boeckh, Michael; Hirsch, Hans H.; Josephson, Filip; Lundgren, Jens D; Nichols, Garrett; Pikis, Andreas; Razonable, Raymund R.; Miller, Veronica; Griffiths, Paul

doi:10.1093/cid/ciw668

Cited by 783 publications

(762 citation statements)

References 12 publications

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“…Moreover, Madi N et al found in renal transplant patients with symptomatic CMV infection the CMV-DNA in serum were all more than 6.5 × 10 4 copies/mL. While at present, only a few studies have evaluated a cut-off value for CMV-DNA in BALF [29, 30]. Drew et al has reported that CMV DNA levels of >5 × 10 5 copies/mL in the patient’s BALF confirmed the presence of CMV pneumonia [31], and Boeckh et al found that CMV viral load > 500 IU/ml in BALF was likely to represent CMV pneumonia in hematopoietic stem cell transplantation patients [32].…”

Section: Discussionmentioning

confidence: 99%

Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: A Retrospective Cohort Study

Jia

et al. 2017

BMC Infect Dis

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Background Pneumocystis jirovecii pneumonia (PJP) and pulmonary cytomegalovirus (CMV) infection are common opportunistic infections among immunocompromised patients. However, few studies have evaluated their co-infection, especially among non-HIV patients. Therefore, we aimed to evaluate the outcomes and prognostic factors among non-HIV patients with PJP according to their CMV infection status.MethodsThis retrospective study evaluated non-HIV patients who were diagnosed with PJP between January 2009 and January2016.The patients were classified and compared according to their pulmonary CMV infection status (positive infection: bronchoalveolar lavage fluid [BALF] CMV DNA loads of >500copies/mL).ResultsAmong 70 non-HIV patients with PJP, we identified 38 patients (54.3%) with pulmonary CMV infection. There was no significant difference in the mortality rates for the two groups (p = 0.15). Pulmonary CMV infection was significantly more common among patients who were receiving glucocorticoids and immunosuppressants, compared to corticosteroids only (p = 0.02). Pulmonary CMV infection was also significantly associated with severe dyspnea, a lower PaO2/FiO2, and the presence of centrilobular nodules (p = 0.008). Higher CMV DNA loads in the BALF were positively associated with mortality (p = 0.012).ConclusionsCombined therapy using corticosteroids and other immunosuppressants may be a risk factor for pulmonary CMV co-infection among patients with PJP. In addition, CMV pneumonia should be considered when centrilobular nodules and/or severe hypoxemia are observed in non-HIV patients with PJP. Furthermore, antiviral treatment should be promptly initiated for patients with a high CMV DNA load in BALF, based on their poor prognosis.

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Section: Discussionmentioning

confidence: 99%

Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: A Retrospective Cohort Study

Jia

et al. 2017

BMC Infect Dis

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“…Therefore prophylaxis against CMV is no longer in use 7, 8. Moreover early preemptive antiviral therapy may lead to an increase of CMV disease after day 100 post transplantation 9.…”

Section: Introductionmentioning

confidence: 99%

Peptide vaccination in the presence of adjuvants in patients after hematopoietic stem cell transplantation with CD4+ T cell reconstitution elicits consistent CD8+ T cell responses

Schmitt¹,

Schmitt²,

Wiesneth³

et al. 2017

Theranostics

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Rationale: Patients receiving an allogeneic stem cell graft from cytomegalovirus (CMV) seronegative donors are particularly prone to CMV reactivation with a high risk of disease and mortality. Therefore we developed and manufactured a novel vaccine and initiated a clinical phase I trial with a CMV phosphoprotein 65 (CMVpp65)-derived peptide.Methods: Ten patients after allogeneic stem cell transplantation received four vaccinations at a biweekly interval. All patients were monitored for CMVpp65 antigenemia. Flow cytometry for CMV-specific CD8+ and γδ T cells as well as neutralizing anti-CMV antibodies were correlated to clinical parameters.Results: The vaccination was well tolerated. Seven of nine patients cleared CMVpp65 antigenemia after four vaccinations and are still free from antigenemia to this day. Two patients with CMV reactivation showed persisting CMV antigenemia. One patient received prophylactic vaccination and did not develop antigenemia. An increase of up to six-fold in frequency of both CMV-specific CD8+ T cells and/or Vδ2negative γδ T cells was detected. Titers of neutralizing antibodies increased up to the tenfold. Humoral and cellular immune responses correlated with clearance of CMV.Conclusion: In summary, CMVpp65 peptide vaccination for patients after allogeneic stem cell transplantation at high risk for CMV reactivation was safe, well tolerated and clinically encouraging. A study in solid-organ transplant patients is ongoing.

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“…EOD for CMV was defined by standard criteria 11 . HHV-6 encephalitis was defined as clinical encephalitis supported by compatible radiographic findings by magnetic resonance imaging in the setting of simultaneous HHV-6 viremia 12 .…”

Section: Methodsmentioning

confidence: 99%

Co-Infections by Double-Stranded DNA Viruses after Ex Vivo T Cell–Depleted, CD34+ Selected Hematopoietic Cell Transplantation

Huang

Kim

Lee

et al. 2017

Biology of Blood and Marrow Transplantation

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Recipients of ex vivo T-cell depleted (TCD) HCT are at risk of infection by double stranded (ds) DNA viruses. We report rates of dsDNA viremia, end-organ disease (EOD), infection-related mortality, and overall survival (OS) in a contemporary cohort of adult TCD HCT recipients routinely monitored for cytomegalovirus (CMV), adenovirus (ADV), human herpesvirus 6 (HHV6) and Epstein-Barr virus (EBV). Health care utilization in the first 6 months post HCT was compared between patients with dsDNA viremia versus no viremia. Observational study of adult patients with acute leukemia and myelodysplastic syndrome who received CD34+ selected, peripheral blood HCT at Memorial Sloan Kettering Cancer Center from March 2012 through December 2014. Patients were prospectively monitored by quantitative polymerase chain (qPCR) assays for CMV, ADV, HHV6 and EBV in whole blood or plasma. The cumulative incidence of viremia(s) at day +180, end-organ disease (EOD) at 1 year, and overall survival at 1 year were estimated by the Kaplan-Meier method and compared by the log-rank test among patient with and without viremia/EOD. Standardized incidence ratios (SIR) were used to compare overall length of hospital stay (LOS), number of readmissions after HCT and length of readmissions through day +180. Of 156 patients, 96 (62%) were CMV recipient seropositive. Patients received grafts from matched related 42 (27%), matched unrelated 86 (55%) or mismatched 28 (18%) donors. Overall, 132 (85%) patients had ≥1viremia, and 52 (33%) patients had ≥2 viremias by day +180. The cumulative incidences for CMV, HHV6, ADV, and EBV viremia were 44%, 61%, 7% and 16%, respectively with median [interquartile range(IQR)] time of onset 28 (25–33), 33(25–47), 60(19–84), and 79 (54–106) days post HCT, respectively. Twenty-eight (18%) patients developed EOD by ds DNA viruses at 1 year post HCT. Treatment for CMV accounted for 91% total antiviral treatment-days. Compared to patients with no viremia, patients with CMV viremia, HHV6 viremia, or ≥ 2 viremias experienced longer LOS (P<0.001) and a higher number of readmissions (P<0.001) by day+ 180. OS at 1-year was 79% and similar between patients with or without ds DNA viremias. EOD was associated with lower 1-year OS (63.4%) vs without EOD (81.1%) (P=0.02). Of 33 patients that died, 10 died due to infection and 7 of the 10 infection-related deaths were due to dsDNA viruses. Viremia by dsDNA viruses occurred in 85% of CD34+ HCT recipients by day +100 and 33% of patients experienced ≥2 viremias by day +180. CMV accounted for the majority of antiviral use. CMV, HHV6 or ≥2 viremias were associated with more readmissions and longer LOS. Overall, one-year OS was 78%. EOD by dsDNA viruses was associated with decreased one-year OS. Infections by ds DNA viruses pose a substantial burden after TCD HCT.

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Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials: Table 1.

Cited by 783 publications

References 12 publications

Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: A Retrospective Cohort Study

Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: A Retrospective Cohort Study

Peptide vaccination in the presence of adjuvants in patients after hematopoietic stem cell transplantation with CD4+ T cell reconstitution elicits consistent CD8+ T cell responses

Co-Infections by Double-Stranded DNA Viruses after Ex Vivo T Cell–Depleted, CD34+ Selected Hematopoietic Cell Transplantation

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