BACKGROUND: Cytomegalovirus (CMV) contributes to morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. Pre-emptive antiviral therapy (PET) reduces the incidence of CMV end-organ disease (EOD), though relevant viral thresholds to initiate PET remain undefined. We evaluated the impact of viral loads (VLs) at PET initiation on virologic and clinical outcomes following pediatric allo-HCT.
METHODS: Single-center retrospective cohort analysis of children who underwent their first allo-HCT from January 2014 to December 2020. Weekly quantitative plasma CMV polymerase chain reaction was performed until Day +100 and PET was initiated once VL exceeded a pre-defined threshold per institutional guidelines. Patients were followed for 1-year post-HCT to evaluate virologic and clinical outcomes including end-organ disease (EOD), overall survival (OS), and non-relapse mortality (NRM).
RESULTS: Among 146 allo-HCT recipients, CMV DNAemia occurred in 40 patients (27%) at a median of 15 days post-HCT (interquartile range 6-28.5). Ten percent (n = 4) had spontaneous resolution of DNAemia, while 90% (n = 36) required PET. PET initiated when CMV VL was ≥ 1000 IU/mL (n = 21) vs when VL < 1000 IU/mL (n = 15) resulted in higher peak CMV VL (12,670 vs. 1284 IU/mL, p = 0.0001) and longer time to CMV DNAemia resolution (36 vs. 24 days, p = 0.035). There were no differences in EOD, OS, or NRM at 12 months post-HCT based on VL at PET initiation.
CONCLUSIONS: Initiating PET when CMV VL was ≥1000 IU/mL resulted in significantly higher peak VL and prolonged DNAemia, with no differences in EOD, OS, or NRM at 12 months post pediatric HCT.

Anelloviridae and Human Pegivirus 1 (HPgV-1) blood burden have been postulated to behave as surrogate markers for immunosuppression in transplant recipients. Here, we assessed the potential utility plasma Torque teno virus (TTV), total Anelloviridae (TAV), and HPgV-1 load monitoring for the identification of allogeneic hematopoietic stem cell transplantation recipients (allo-HSCT) at increased risk of infectious events or acute graft versus host disease (aGvHD). In this single-center, observational study, plasma TTV DNA, TAV DNA, and HPgV-1 RNA loads were monitored in 75 nonconsecutive allo-HSCT recipients (median age, 54 years). Monitoring was conducted before at baseline or by days +30, +60, +90, +120, and +180 after transplantation. Pneumonia due to different viruses or Pneumocystis jirovecii, BK polyomavirus-associated haemorrhagic cystitis (BKPyV-HC), and Cytomegalovirus DNAemia were the infectious events considered in the current study. Kinetics of plasma TTV, TAV DNA, and HPgV-1 RNA load was comparable, with though and peak levels measured by days +30 and day +90 (+120 for HPgV-1). Forty patients (53%) developed one or more infectious events during the first 180 days after allo-HSCT, whereas 29 patients (39%) had aGvHD (grade II-IV in 18). Neither, TTV, TAV, nor HPgV-1 loads were predictive of overall infection or CMV DNAemia. A TTV DNA load cut-off ≥4.40 log10 (pretransplant) and ≥4.58 log10 (baseline) copies/mL predicted the occurrence of BKPyV-HC (sensitivity ≥89%, negative predictive value, ≥96%). TTV DNA loads ≥3.38 log10 by day +30 anticipated the occurrence of aGvHD (sensitivity, 90%; negative predictive value, 97%). Pretransplant HPgV-1 loads were significantly lower (p = 0.03) in patients who had aGvHD than in those who did not. Monitoring of TTV DNA or HPgV-1 RNA plasma levels either before or early after transplantation may be ancillary to identify allo-HSCT recipients at increased risk of BKPyV-HC or aGvHD.

UNASSIGNED: The prevalence and reactivating pattern of cytomegalovirus (CMV) among renal transplant recipients in Sri Lanka is scarce. The study was aimed to describe the replication patterns of CMV in post-renal transplant recipients who were on pre-emptive therapy and identify the risk factors and time period for CMV reactivating during the 1st year of transplantation and provide an insight into the selection of pre-emptive therapy in the local setting.
UNASSIGNED: A retrospective and cohort study was conducted, enrolling renal transplant recipients who have completed routine 1-year follow-up for pre-emptive management at the National Hospital, Kandy, from January 2016 to January 2021. CMV quantitative polymerase chain reaction results and demographic data of enrolled recipients were analyzed to investigate the CMV replication pattern and risk factors. Categorical data were analyzed using Pearson\'s Chi-square test, considering P < 0.05 statistically significant. Continuous variables were presented as percentages.
UNASSIGNED: Two hundred and fifty-one renal transplant recipients\' data were included in the study. Of them, 75.70% were male patients, and the mean age of the study population was 43.25 years. CMV DNAemia incidence was 56.57% during the 1st year of post-renal transplantation. Only 9.16% had developed more than 104 IU/mL or significant DNAemia. Sex and donor type were not risk factors for CMV reactivation. However, the recipient\'s age was significantly associated with CMV viraemia among renal transplant recipients.
UNASSIGNED: Considering the low incidence of significant viraemia among the study population, pre-emptive treatment would be the cost-effective strategy for management of the post-renal transplant recipients in local settings.

The current study evaluates the clinical effect of sirolimus exposure on the occurrence of cytomegalovirus (CMV) DNAemia necessitating preemptive antiviral therapy. A total of 167 consecutive recipients of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received sirolimus- and tacrolimus-based graft-versus-host disease (GVHD) prophylaxis and whose CMV serostatus was positive for donors and/or recipients were included in this multicenter retrospective study. A parametric model with consecutive sirolimus blood levels describing the time to CMV DNAemia-RAT was developed using NONMEM version 7.4. Overall, 122 of 167 patients (73%) were allografted from an unrelated donor, and the donor CMV-serostatus was negative in 51 cases (31%). Fifty-six recipients (34%) developed CMV DNAemia necessitating preemptive therapy, with a cumulative incidence of 36% at a median follow-up of 25 months. Time to CMV DNAemia necessitating preemptive therapy was best described using a Gompertz function. CMV DNAemia necessitating preemptive therapy-predicting factors were antithymocyte globulin-based conditioning regimen (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.1 to 4.1; P < .01) and sirolimus concentration (HR, .94; 95% CI, .87 to .99; P < .01). The risk of CMV DNAemia-RAT decreased by 6% for each 1 ng/mL increase in sirolimus trough concentration. In conclusion, we provide evidence on the association between sirolimus blood concentration and incidence of CMV DNAemia necessitating preemptive therapy in allo-HSCT recipients. Moreover, this study presents the first predictive model describing the time to CMV DNAemia necessitating preemptive antiviral therapy as a function of sirolimus drug concentration.