Dataset Information

Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections.

ABSTRACT:

Background

Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients.

Methods

The CMV doubling time of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of recipients with a high diagnostic CMV viral load (≥ 18,200 IU/mL) were explored using mathematical simulation.

Findings

The overall median doubling time was 4.3 days (IQR 2.5-7.8) and was not influenced by prior CMV immunity, or type of transplantation (p > 0.4). Assuming a fixed doubling time of 1.3 days and screening intervals of 7 or 10 days, 11.1% and 33.3% were projected to have a high CMV viral load at diagnosis, compared to 1.4% and 4.3% if the doubling time varies as observed in our cohort. Consistently, 1.9% of recipients screened weekly had a high diagnostic virus load.

Interpretation

Screening intervals can be extended to 10 days in cohorts with comparable CMV doubling time, whereas shorter than 7 days is required in cohorts with shorter doubling times to maintain pre-emptive screening quality.

SUBMITTER: Lodding IP

PROVIDER: S-EPMC4534685 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections.

Lodding I P IP Sengeløv H H da Cunha-Bang C C Iversen M M Rasmussen A A Gustafsson F F Downing J G JG Grarup J J Kirkby N N Frederiksen C M CM Mocroft A A Sørensen S S SS Lundgren J D JD

EBioMedicine 20150508 7

<h4>Background</h4>Cytomegalovirus (CMV) infection in transplant recipients is reported to replicate with a doubling time of 1.2-2 days, and weekly screening is recommended for early diagnosis. We re-evaluated these features in our cohort of transplant recipients.<h4>Methods</h4>The CMV doubling time of the first CMV infection in the first year post-transplant could be calculated for 193 recipients of haematopoietic stem cell or solid organ transplantation. Factors determining the proportion of ...[more]

PMID: 26288842

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Project description:IntroductionOpportunistic viral infections cause extensive morbidity and mortality in kidney transplant recipients (KTRs). Low serum albumin levels before and after transplant have been associated with negative outcomes. However, it is uncertain whether serum albumin levels before transplantation are associated with the risk for post-transplantation opportunistic BK polyomavirus (BKV) or cytomegalovirus (CMV).MethodsWe reviewed all KTRs transplanted at our institution between 1 January 2005 and 31 December 2015 with serum albumin measured within 45 days before transplantation in a retrospective observational cohort study. Selected patients were stratified into 3 groups: normal albuminemia (≥3.5 g/dl), moderate hypoalbuminemia (3.49-2.5 g/dl), and severe hypoalbuminemia (<2.5 g/dl). Patients were observed for post-transplantation BKV or CMV according to standard of care.ResultsWe included 1717 patients in this study; 72.3% had normal serum albumin, 26.3% had moderate hypoalbuminemia, and 1.5% had severe hypoalbuminemia. Moderate and severe hypoalbuminemia incurred a higher risk for BKV compared with normal serum albumin levels in univariable analysis (moderate hypoalbuminemia: hazard ratio [HR] = 1.5; 95% confidence interval [CI], 1.14-1.90; P = .003); severe hypoalbuminemia: HR = 2.15; 95% CI, 1.01-4.56; P = 0.05). Although not significant after multivariable adjustment, there was still 18% increased risk in moderate hypoalbuminemia and 64% in severe hypoalbuminemia for BKV compared with the normal albumin group. Moderate hypoalbuminemia was associated with a higher risk for CMV infection than normal serum albumin levels in multivariable analysis, although it was not statistically significant (HR = 1.15; 95% CI, 0.36-3.64; P = 0.81).ConclusionsThese findings suggest that pretransplantation hypoalbuminemia is associated with a higher risk for post-transplantation BKV and possibly CMV. More intense screening is warranted for these viruses in recipients with pretransplant hypoalbuminemia.

Project description:BackgroundTriplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT).ObjectiveTo determine the safety and efficacy of Triplex.DesignFirst-in-patient, phase 2 trial. (ClinicalTrials.gov: NCT02506933).Setting3 U.S. HCT centers.Participants102 CMV-seropositive HCT recipients at high risk for CMV reactivation.InterventionIntramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens.MeasurementsThe primary outcomes were CMV events (CMV DNA level ≥1250 IU/mL, CMV viremia requiring antiviral treatment, or end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were probably or definitely attributable to injection.ResultsA total of 102 patients (51 per group) received the first vaccination, and 91 (89.2%) received both vaccinations (46 Triplex and 45 placebo). Reactivation of CMV occurred in 5 Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46 [95% CI, 0.16 to 1.4]; P = 0.075). No Triplex recipient died of nonrelapse causes during the first 100 days or had serious AEs, and no grade 3 or 4 AEs related to vaccination were observed within 2 weeks after vaccination. Incidence of severe acute GVHD after injection was similar between groups (hazard ratio, 1.1 [CI, 0.53 to 2.4]; P = 0.23). Levels of long-lasting, pp65-specific T cells with effector memory phenotype were significantly higher in Triplex than placebo recipients.LimitationThe lower-than-expected incidence of CMV events in the placebo group reduced the power of the trial.ConclusionNo vaccine-associated safety concerns were identified. Triplex elicited and amplified CMV-specific immune responses, and fewer Triplex-vaccinated patients had CMV viremia.Primary funding sourceNational Cancer Institute and Helocyte.

Dataset Information

Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections.

Background

Methods

Findings

Interpretation

Publications

Clinical Application of Variation in Replication Kinetics During Episodes of Post-transplant Cytomegalovirus Infections.

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