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Backgrounds:

Human adenovirus (hAdV) infection constitutes an important cause of morbidity and mortality in immunocompromised patients as solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients.

Cidofovir is the most prescribed treatment even though its use is controversial specially in asymptomatic patients. Strategies like reducing immunosuppression, or lymphocyte infusions have not yet been well described.

This study aims to describe the impact and therapeutic management of hAdV infection in immunocompromised patients

Methods

Retrospective study examining episodes of positive hAdV viremia (>1.000 copies/mL) in immunocompromised hosts during a four-year follow-up (2017-2021) at a reference centre. Demographic, clinical, epidemiological, and microbiological data, lymphocyte count, therapeutic management, and outcome were collected and analysed.

Results:

49 immunosuppressed patients (median age 9 years; interquartile range IQR 1.0-16.0) were included. Main causes of immunosuppression were HSCT (38/49: 77.6%), hematologic malignancies (30/49; 61.2%), and SOT (11/49: 22.4%).

25 patients (51%) were symptomatic (mainly febrile syndrome and diarrhoea). Thirteen patients (26.5%) presented a viral coinfection with CMV or BK virus. Cidofovir was prescribed in 24 patients (49%). Other therapeutic measures included administration of intravenous immunoglobulins (18.4%), reducing immunosuppression (14.3%) and memory T-cell infusion (12.2%).

Cidofovir use was significantly (p<0.05) associated with presence of hAdv symptoms, lower lymphocyte count, ICU admission and high viral load (Table 1).

Despite treatment, 11 patients (45.8%) presented persistent positive viremias (associated with lower lymphocyte count p<0.05) and three patients died because hAdV infection (acute liver failure, septic shock).

Conclusions/Learning Points:

hAdV infections had high morbidity and mortality in our series. Patients with low lymphocyte count are at higher risk of persistent positive viremias and short-term survival. We did not observe a clear association between resolution of infection and Cidofovir use.

Backgrounds:

Cytomegalovirus (CMV) infection is the most common viral infection after liver transplantation (LT). Preemptive therapy (PET) is an alternate approach in which antiviral therapy is initiated for early asymptomatic CMV viremia. However, the optimal viral load (VL) cut-off for initiating PET remains controversial. Therfore, this study aimed to evaluate the incidence of CMV infection, risk factors, and outcomes of PET after using different VL cut-offs in pediatric LT.

Methods

We retrospectively reviewed 126 patients aged 0-18 years who underwent LT between March 2011 and August 2020. CMV viremia was regularly monitored using quantitative nucleic acid amplification in all patients. Data on clinical characteristics and potential risk factors, including CMV serostatus, acute cellular rejection (ACR), and immunosuppressive drugs were collected. CMV infection and diseases were defined according to International guidelines. Additionally, clinical outcomes for starting PET at low VL cut-off (< 2000 copies/mL) and high VL cut-off (≥ 2000 copies/mL) were compared.

Results:

In total, 90 of 126 patients (71%) developed CMV infection with a median onset of 30.2 days (Interquartile range (IQR) 13, 39). In a univariate analysis, factors associated with CMV infection included younger age, CMV D+/R-, ACR, and higher corticosteroid dosage. Only corticosteroid dosage remained associated with CMV infection in a multivariate analysis [adjusted odds ratio (OR) 116.9; 95% confidence interval (CI) 17.75-770.98; p<0.001]. Recurrent CMV infection, CMV diseases, ACR, and Epstein-Barr Virus infection did not differ significantly between the low and the high VL cut-off groups.

Conclusions/Learning Points:

The incidence of CMV infection was high in pediatric LT. Higher corticosteroid dosage was associated with CMV infection. Additionally, using CMV VL cut-off at 2000 copies/mL for initiating antiviral therapy seems to be a practical and effective strategy to prevent CMV diseases.

Backgrounds:

Epstein-Barr virus (EBV) infections cause significant morbidity and mortality in pediatric SOTR. Post-transplant lymphoproliferative disorder is a devastating complication of EBV infection in SOTR. Contemporary data on rates of EBV DNAemia and subsequent PTLD in pediatric SOTR are limited.

Methods

A retrospective cohort study of patients ≤ 21 years of age who received lung, heart, liver, kidney, or multi-organ transplants at TCH between 2010-2018 was completed. Primary outcome was quantifiable EBV DNAemia. Associations with EBV DNAemia were measured using Fisher exact test and multivariate logistic regression. Survival analysis and time to EBV DNAemia were assessed using Kaplan-Meier method.

Results:

Among 687 SOTR, 43% (295) had quantifiable EBV DNAemia; this included 45% (39/87) lung, 62% (161/259) liver, 39% (59/152) heart, 64% (9/14) multi-organ, and 15% (27/175) kidney recipients. Median time to quantifiable DNAemia for patients that developed EBV was 573 (0 – 3237) days (Figure 1). High-risk EBV status (D+/R-) [OR 2.76, 95% CI (1.6 – 4.7), and having a liver transplant [10.84 (6.4 – 18.4)] were associated with the development of EBV DNAemia.

DNAemia was not associated with sex, ethnicity, or era of transplantation. Induction therapy was collinear with organ transplanted and could not be assessed. There was no difference in survival during the study follow-up period (1–9 years) for SOTR with vs. without DNAemia (p=0.08). Overall PTLD occurred in 4% (26/687) of SOTR; this included 6% (5/87) lung, 2% (6/259) liver, 8% (12/152) heart, 0% (0/14) multiorgan, and 2% (3/175) kidney recipients.

Conclusions/Learning Points:

This large contemporary cohort of pediatric SOTR demonstrates high overall rates of EBV DNAemia and relatively low rates of PTLD. Heart SOTR had the highest rate of PTLD, suggesting that further interventions targeting this group may be warranted.