scholarly journals No association of genetic variants in TLR4, TNF-α, IL10, IFN-γ, and IL37 in cytomegalovirus-positive renal allograft recipients with active CMV infection—Subanalysis of the prospective randomised VIPP study

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0246118
Author(s):  
Pascale Mazzola ◽  
Elke Schaeffeler ◽  
Oliver Witzke ◽  
Martin Nitschke ◽  
Volker Kliem ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Renal Allograft ◽  
Graft Loss ◽  
Asymptotic Independence ◽  
Solid Organ ◽  
Negative Outcomes ◽  
Cmv Infection ◽  
Tnf Α ◽  
Ifn Γ ◽  
Cmv Disease

Background Cytomegalovirus (CMV) infection is amongst the most important factors complicating solid organ transplantation. In a large prospective randomized clinical trial, valganciclovir prophylaxis reduced the occurrence of CMV infection and disease compared with preemptive therapy in CMV-positive renal allograft recipients (VIPP study; NCT00372229). Here, we present a subanalysis of the VIPP study, investigating single nucleotide polymorphisms (SNPs) in immune-response-related genes and their association with active CMV infection, CMV disease, graft loss or death, rejection, infections, and leukopenia. Methods Based on literature research ten SNPs were analyzed for TLR4, three for IFN-γ, six for IL10, nine for IL37, and two for TNF-α. An asymptotic independence test (Cochran-Armitage trend test) was used to examine associations between SNPs and the occurrence of CMV infection or other negative outcomes. Statistical significance was defined as p<0.05 and Bonferroni correction for multiple testing was performed. Results SNPs were analyzed on 116 blood samples. No associations were found between the analyzed SNPs and the occurrence of CMV infection, rejection and leukopenia in all patients. For IL37 rs2723186, an association with CMV disease (p = 0.0499), for IL10 rs1800872, with graft loss or death (p = 0.0207) and for IL10 rs3024496, with infections (p = 0.0258) was observed in all patients, however did not hold true after correction for multiple testing. Conclusion The study did not reveal significant associations between the analyzed SNPs and the occurrence of negative outcomes in CMV-positive renal transplant recipients after correction for multiple testing. The results of this association analysis may be of use in guiding future research efforts.

Functional Comparison and Longitudinal Assessment of Tri-Functional T-Cells Recognizing CMV pp65 and IE-1 Polypeptides in Hematopoietic Stem Cell and Solid Organ Transplant Recipients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2936-2936
Author(s):  
Don J. Diamond ◽  
Simon F. Lacey ◽  
Corinna La Rosa ◽  
Wendy Zhou ◽  
Ghislaine Gallez-Hawkins ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Specific Ctls ◽  
Tnf Α ◽  
Ifn Γ ◽  
Cmv Disease

Abstract Reconstitution of adaptive T-cell responses to human cytomegalovirus (CMV) is critical to protection from CMV disease following hematopoietic stem cell (HSCT) or solid organ transplantation (SOT). However, there is an incomplete understanding of which CMV antigens and epitopes are most crucial to providing protective responses. The functional status of cytotoxic T-lymphocyte (CTL) populations recognizing cytomegalovirus IE-1 and pp65 polypeptides was investigated in PBMC from either HSCT or SOT recipients. Our previous finding of differing levels of degranulation between CMV IE1 and pp65/pp50 specific T-cells was complicated by the possibility that differences were epitope and/or HLA-specific. We generalized the approach using a combined flow-based CD107a/b degranulation/mobilization and intracellular cytokine (ICC) assays using peptide libraries as antigens. These assays indicated that a significantly higher proportion of pp65-specific CTLs were in a more mature functional state compared to IE-1-specific CTLs. Degranulation/multicytokine ICC assays also indicated that a significantly higher proportion of the pp65-specific versus IE-1-specific CTLs secreted both IFN-γ and TNF-α, in addition to possessing greater cytotoxic potential. These results support our earlier findings of functional differences between CTLs recognizing individual epitopes within the IE-1 and pp65 antigens in HSCT recipients, and extend them to a broader array of HLA-restricted responses to those antigens. A report that a subset of HIV-1 specific CTLs capable of producing both IFN-γ and TNF-α was associated with improved cytotoxic activity prompted us to investigate whether degranulation, a functional correlate of cytotoxicity, was positively associated with dual cytokine production and predicted differences between IE1 and pp65-specific CD8+ T-cells. A higher proportion of pp65-specific compared to IE1-specific T-cells were present in the trifunctional IFN-γ+,TNF-α+, CD107+ population (p=0.008) in HSCT recipients. We have extended these findings to investigate the role of donor CMV status in terms of functional maturity of CMV-specific T cell response in transplant recipients. T cell maturation/function may act as a mechanistic correlate to the survival advantage of recipients receiving a stem-cell graft from CMV sero-positive donors. These principles have also been applied to investigations of a high risk population of sero-negative recipients of a sero-positive liver allograft. Data from this study will also be reviewed in the context of the model of trifunctional T cells being indicative of enhanced protective capacity against CMV disease and associated with survival.

scholarly journals Use of ganciclovir for cytomegalovirus infection.

1992 ◽  
Vol 2 (12) ◽  
pp. S270
Author(s):  
T E Nevins ◽  
D L Dunn
Keyword(s):  
Graft Loss ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
University Of Minnesota ◽  
Cmv Infection ◽  
Seronegative Patient ◽  
Patient Morbidity ◽  
Infected Cells ◽  
The University ◽  
Cmv Disease

Ganciclovir (9-(1,3-dihydroxy-2-propoxymethyl) guanine, DHPG) is an acyclovir analog with excellent antiviral activity against human cytomegalovirus (CMV). Clinically, CMV infection occurs in from 60 to 90% of all renal transplant recipients and it is responsible for significant patient morbidity and graft loss. The likelihood of infection is closely related to the CMV status of both donor and recipient, with the greatest risk arising in the combination of a seronegative patient receiving a seropositive organ. Intracellularly, DHPG is converted to DHPG-triphosphate, which competitively inhibits DNA polymerase. This conversion is accelerated up to 10-fold in virally infected cells, providing some selectivity of action. Uncontrolled studies demonstrated DHPG efficacy in CMV disease, but experience in children remains limited. Although bone marrow suppression is a major immediate toxicity, long-term concerns about carcinogenesis and infertility mandate careful patient selection. Recently at the University of Minnesota, 93 solid organ recipients (45 renal transplants) including some children have been treated for tissue-invasive CMV with DHPG. All had a characteristic clinical picture and either a positive CMV culture or a biopsy with CMV inclusions. The patients received i.v. DHPG (10 mg/kg/day) with appropriate adjustments for renal function. In renal allograft recipients, 89% recovered within 30 days, although 21% had to be retreated with DHPG. Although no patient died, allograft survival was significantly reduced (P = 0.02). An additional subgroup of patients (N = 18) who had both biopsy-proven rejection and invasive CMV disease were simultaneously treated for both processes. All of these patients recovered from their CMV infection, but two grafts were lost to rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 88
Author(s):  
Smaranda Gliga ◽  
Melanie Fiedler ◽  
Theresa Dornieden ◽  
Anne Achterfeld ◽  
Andreas Paul ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Cellular Assays ◽  
Risk Patients ◽  
Ifn Γ ◽  
Liver Transplant Recipients

To estimate protection from cytomegalovirus (CMV) replication after solid organ transplantation, CMV serology has been considered insufficient and thus CMV immunity is increasingly assessed by cellular in vitro methods. We compared two commercially available IFN-γ ELISpot assays (T-Track CMV and T-SPOT.CMV) and an IFN-γ ELISA (QuantiFERON-CMV). Currently, there is no study comparing these three assays. The assays were performed in 56 liver transplant recipients at the end of antiviral prophylaxis and one month thereafter. In CMV high- or intermediate-risk patients the two ELISpot assays showed significant correlation (p < 0.0001, r > 0.6) but the correlation of the ELISpot assays with QuantiFERON-CMV was weaker. Results of both ELISpot assays were similarly predictive of protection from CMV-DNAemia ≥500 copies/mL [CMV pp65 T-SPOT.CMV at the end of prophylaxis: area under curve (AUC) = 0.744, cut-off 142 spot forming units (SFU), sensitivity set to 100%, specificity 46%; CMV IE-1 T-Track CMV at month 1: AUC = 0.762, cut-off 3.5 SFU, sensitivity set to 100%, specificity 59%]. The QuantiFERON-CMV assay was inferior, reaching a specificity of 23% when setting the sensitivity to 100%. In conclusion, both CMV-specific ELISpot assays appear suitable to assess protection from CMV infection/reactivation in liver transplant recipients.

scholarly journals 1744. CMV Infection and Management Among Pediatric Solid-Organ Transplant Recipients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S639-S639
Author(s):  
Anna Sharova ◽  
Despoina M Galetaki ◽  
Molly Hayes ◽  
Lauren Gianchetti ◽  
Laura A Vella ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Solid Organ Transplant ◽  
First Year ◽  
Invasive Infection ◽  
Solid Organ ◽  
Cmv Infection ◽  
Research Support ◽  
Free Survival ◽  
Medium Risk ◽  
Cmv Disease

Abstract Background Our institution provides universal CMV prophylaxis (PPX) for all high (D+/R-) and medium risk (R+) solid-organ transplant (SOT) recipients. We sought to evaluate this practice by assessing CMV infection and disease within the first year of SOT. Methods Retrospective cohort study of all children undergoing first SOT at Children’s Hospital of Philadelphia from January 2012 to October 2017. We identified recipients with CMV infection (detection of CMV DNA in body fluid/tissue with or without symptoms) and disease (symptomatic or tissue-invasive infection) in the first year after SOT. We calculated the rate of CMV infection and compared CMV-free survival based on SOT type and CMV risk using log-rank tests. Results 244 children received 246 SOTs: 90 liver, 70 kidney, 59 heart, 27 lung. In total, 39 children (16%) had 49 CMV infections in the first year after SOT, including 29% of high (n = 21/72) and 23% of medium risk recipients (n = 16/69). The fraction of each organ type with CMV infection was similar (Figure 1, P = 0.33). Among high and medium risk recipients, all of whom received PPX, the incidence rate of CMV infection in the first year post-SOT was similar: 10.1 vs. 7.8/10,000 days (P = 0.22). There were no differences in CMV-free survival by organ (Figure 2, log-rank P = 0.25) or between high and medium risk recipients (Figure 3, log-rank P = 0.46). In total, 22% (n = 10/45) of CMV infections in high/medium risk patients occurred while on PPX; half were in the setting of reduced PPX dosing or within 2 weeks of SOT. Of the 35 CMV infections post-PPX, the median time to detection of CMV after PPX was 39 days (IQR 28–98). There were 11 cases (6 high, 5 medium risk) of CMV disease: 6 CMV syndrome, 2 hepatitis, 2 pneumonitis, 1 GI disease. Valganciclovir was more often used for treatment of asymptomatic infections than for CMV disease (79% vs. 33%, P = 0.03). All-cause mortality in the first year post-SOT was similar among those with and without CMV infections (7.7 vs. 6.3%, P = 0.76) and among those with and without CMV disease (9.1 vs. 5.2%, P = 0.57). Conclusion CMV infection was common in high and medium risk SOT recipients in the first year following SOT, and most infections occurred off of PPX. Our data suggest that the highest risk period for CMV infection is in the first months after PPX, and that monitoring may be most useful after PPX has been stopped or when PPX doses are reduced. Disclosures Kevin J. Downes, MD, Merck: Grant/Research Support, Research Grant; Pfizer: Grant/Research Support.

scholarly journals Poor NKG2C+ Adaptive NK Cell Recovery at Early Stage after Allo-HSCT Increased the Occurrence of Refractory Cytomegalovirus Infection

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 360-360
Author(s):  
Xingxing Yu ◽  
Xiangyu Zhao ◽  
Xunhong Cao ◽  
Xuefei Liu ◽  
Xuying Pei ◽  
...  
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Solid Organ ◽  
Cmv Infection ◽  
Cell Recovery ◽  
Post Transplantation ◽  
Cell Counts ◽  
Ifn Γ ◽  
The Absolute ◽  
Cmv Reactivation

Abstract Backgroud: Refractory cytomegalovirus (CMV) infection remains important causes of morbidity and mortality after allogeneic hematopoietic stem cells transplantation (allo-HSCT). Previous researches reported that adaptive immunity, such as CD8+ CMV-CTL, plays an important role in the in the control of refractory CMV infection. In mouse, Lanier et al. found there existed subsets of adaptive NK cells with the features of expanding, contracting after control of mouse CMV, and generating long-lived "memory" NK cells. In human, these adaptive NK cells were initially identified based on the high expression of the NKG2C which against HCMV through their cytotoxic potential and the production of TNF-α and IFN-γ upon Ab-mediated stimuli in vitro. Meanwhile, the expression levels of the NKG2C+ adaptive NK cells has been positively correlated with the NKG2C copy number. Several researchers had found that NKG2C+ adaptive NK cells persistent expanded and were potent producers of IFN-γ during CMV reactivation after solid-organ transplant or allo-HSCT. However, the role of NKG2C+ adaptive NK cells on refractory CMV reactivation were still unknown. Whether the rapid reconstitution of NKG2C+ adaptive NK cells can reduce the refractory CMV reactivation merit to be investigated. Aims:In this research, we had investigated the impacts of the quantity and quality recovery of NKG2C+ adaptive NK cells on the occurrence of refractory CMV infection. Method: At first, continuous 364 patients underwent allo-HSCT since June 2012 to February 2016 were prospectively enrolled and we retrospectively analyzed the correlationship between their donor NKG2C genotype and refractory CMV infection occurrence post transplantation. Secondly, the second cohort comprising continuous 125 patients underwent allo-HSCT since May 2016 to April 2017 were prospectively enrolled to analyzed the effect of donor NKG2C genotype on NKG2C+ adaptive NK cell recovery as well as the effect of NKG2C+ adaptive NK cell recovery on refractory CMV infection. The cytotoxicity of reconstituting NKG2C+ adaptive NK cells were evaluated against K562 cells, AD169 CMV stain infected MRC-5 cells, and UL40 peptide pulsed 721.221 cells to detect the anti-tumor or anti-CMV function of NKG2C+ adaptive NK cells. Results: Firstly, from the first cohort, we found that donor NKG2C gene deletion was an independent prognostic factor for refractory CMV reactivation (P=0.010) through the multivariate analysis. Then, through in-depth investigation from the second cohort, we found that the absolute cell counts recovery and anti-tumor function of NKG2C+ adaptive NK cells were both significantly lower in patients accepting NKG2C+/del donor than those patients accepting NKG2C+/+ donors at day 30, 90, and180, respectively after transplantation. There was no NKG2C+ adaptive NK cell recovery post transplantation in the patients who accepted NKG2Cdel/del donors. Meanwhile, anti-CMV function recovery of NKG2C+ adaptive NK cells in patients with NKG2C+/del donors were significantly lower than those patients with NKG2C+/+ donors at day 30 post transplantation. Furthermore, we further analyzed the relationship between the early reconstitution of NKG2C+ adaptive NK cells and refractory CMV infection occurrence. The patients were divided into three groups: no CMV, CMV reactivation (persistent time of CMV infection <2 weeks), and refractory CMV infection (persistent time of CMV infection>2 weeks). We found that the absolute cell counts of NKG2C+ adaptive NK cells in refractory CMV group was significantly lower than that of other two groups at day 30 transplantation. When the patients were devided into high and low level groups based on the ROC cut-off percentage of NKG2C+ adaptive NK cells (1.42%), the result revealed that the patients with lower level of NKG2C+ adaptive NK cells at day 30 post-HSCT had an higher cumulative incidence rate of refractory CMV infection (81.1%) comparing with the higher one (40.5%) (P=0.0014). Moreover, Cox regression model further demonstrated that the lower level of NKG2C+ adaptive NK cells at day 30 post-HSCT was significantly associated with refractory CMV infection (HR=2.578, 95% CI 1.379-4.21, P=0.003). Summary/Conclusion: Our results indicated that donor NKG2C deletion damaged the reconstitution of NKG2C+ adaptive NK cells after allo-HSCT, therefore increased the occurrence of refractory CMV infection post transplantation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Analytical Performance and Clinical Utility of a Nucleic Acid Sequence-Based Amplification Assay for Detection of Cytomegalovirus Infection

2000 ◽  
Vol 38 (11) ◽  
pp. 3994-3999 ◽  
Author(s):  
Donald J. Witt ◽  
M. Kemper ◽  
Andrew Stead ◽  
P. Sillekens ◽  
Christine C. Ginocchio ◽  
...  
Keyword(s):  
Cell Culture ◽  
Nucleic Acid ◽  
Multiple Testing ◽  
Clinical Utility ◽  
Limit Of Detection ◽  
Organ Transplant ◽  
Nucleic Acid Sequence ◽  
Solid Organ ◽  
Cmv Infection ◽  
Nasba Assay

A nucleic acid sequence-based amplification (NASBA) assay for qualitative detection of human cytomegalovirus (CMV) pp67 mRNA was evaluated in a multicenter study. Negative results were obtained for all specimens from 50 CMV-seronegative and 50 CMV-seropositive low-risk whole-blood donors. No interference with CMV mRNA amplification was observed in the testing of 288 specimens containing various potential interfering substances, nonspecifically reacting substances (including mRNA from other herpesviruses), and three anticoagulants. A total of 95% (50 of 51) of CMV-positive (cell culture- and antigenemia immunofluorescence [AG-IFA]-positive) clinical specimens were positive by the NASBA assay. Results from different operators over multiple testing days were consistent for each of four panel members containing different concentrations of CMV mRNA, indicating the reproducibility of the assay. The estimated 95% reliable upper detection limit of the assay was 600 mRNA copies; the lower limit of detection was less than 25 mRNA copies. The clinical utility of the assay was evaluated with longitudinally collected specimens from solid-organ transplant patients (n = 21). A total of 98% (81 of 83) of the specimens from CMV-negative patients were negative by the NASBA assay, while 90% (10 of 11) of patient specimens that were positive by cell culture or AG-IFA were positive by the NASBA assay. Positive NASBA assay results were obtained earlier than AG-IFA or cell culture results for 55% of the patients and at the same time for the remainder of the patients (45%). The overall agreement between the NASBA assay and current reference tests was 86% when active CMV infection was present. These studies indicate that the CMV pp67 mRNA NASBA assay has reproducible and sensitive performance characteristics that should enable more rapid diagnosis of CMV infection.

scholarly journals Clinical Relevance of Direct Quantification of pp65 Antigenemia Using Flow Cytometry in Solid Organ and Stem Cell Transplant Recipients

2000 ◽  
Vol 38 (9) ◽  
pp. 3143-3149 ◽  
Author(s):  
Anne-Sophie Poirier-Toulemonde ◽  
Noel Milpied ◽  
Diego Cantarovich ◽  
Jean-François Morcet ◽  
Sylviane Billaudel ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Laboratory Data ◽  
Solid Organ ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Pp65 Antigenemia ◽  
Cmv Disease ◽  
Direct Quantification

A total of 1,305 blood samples from 85 solid organ transplant (SOT) recipients and 25 stem cell transplant (SCT) recipients at risk for cytomegalovirus (CMV) infection were prospectively collected and tested using the shell vial assay (SVA) and a leukocytic qualitative PCR (q-PCR). Of these, 462 specimens were further tested by direct quantification of CMV antigenemia by flow cytometry (FC-Ag), 125 were tested with a quantitative competitive PCR, and 200 were tested for pp65 antigenemia using the slide method (S-Ag). Laboratory data were statistically analyzed according to the presence of CMV-related symptoms. In SOT and SCT recipients, active CMV infection occurred in 63.5 and 36%, respectively, and CMV disease occurred in 53 and 24%, respectively. FC-Ag results correlated better with q-PCR and S-Ag than with SVA. The first test found to be positive during follow-up was FC-Ag in 73% of cases. In SOT recipients, FC-Ag showed the highest sensitivity and negative predictive value for the diagnosis of any grade of CMV disease. For FC-Ag, the threshold beyond which CMV disease was highly probable seemed to lie at 0.20% positive polymorphonuclear leukocytes. FC-Ag appears to be a useful test for the early detection of CMV infection and the prediction of CMV disease.

QuantiFERON®-CMV for Immune-Monitoring in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4369-4369
Author(s):  
Enrico Morello ◽  
Elisabetta Pagani ◽  
Vladia Monsurrò ◽  
Irene Cavattoni ◽  
Silvia Coin ◽  
...  
Keyword(s):  
At Risk ◽  
Whole Blood ◽  
Cmv Infection ◽  
Mortality And Morbidity ◽  
Viral Therapy ◽  
Ifn Γ ◽  
Cmv Disease ◽  
Anti Viral Therapy ◽  
Related Mortality

Abstract Background: CMV infection represents a major complication of allo-SCT affecting transplant related mortality and morbidity. Anti-viral therapy is toxic and prolonged treatment could affect graft function. Monitoring specific immune response against CMV could optimize the timing for anti-viral therapy administration in order to avoid related toxicity and to reduce CMV related mortality and morbidity. A recent ELISA based test (QuantiFERON®-CMV) could measure specific (anti-HCMV) and aspecific production of IFN-γ in whole blood. Aims: to test the reliability of QuantiFERON®-CMV in a cross sectional study in order to identify patients at risk of CMV disease after alloHSCT. Methods: QuantiFERON®-CMV is an in vitro diagnostic test using a peptide cocktail simulating human cytomegalovirus proteins (CMV) to stimulate cells in heparinised whole blood. Detection of interferon-γ (IFN-γ) by ELISA is used to identify in vitro responses to these peptide antigens that are associated with CMV infection. The IFN-γ response in the CMV Ag tube is considered positive if &gt; 0.2 UI/mL as defined by the manufacturer. The mitogen-stimulated plasma sample was used as an IFN-γ positive control (PC) for each specimen tested. CMV reactivation and disease were defined according EBMT recommendations. Results: Among 92 tests no correlation between pp65 antigenemia and IFN-γ production was proved (p=0,346). However, among the 41 tests showing lower levels of anti-HCMV IFN-γ production (&lt;0.2 IU/mL) 8 tests belonging 4 patients were associated with CMV disease, whereas among the 51 tests showing higher levels of anti-HCMV IFN-γ production (&gt;=0.2 IU/mL) none were associated with CMV disease (p=0.001), RR 2.5 (CI95% 1.951–3.321). Conclusions: QuantiFERON®-CMV doesn’t seem to represent a significant reliable test for risk of viremia after alloHSCT, but patients with prolonged lower levels of anti-HCMV IFN-γ production (&lt;0.2 IU/mL) are at risk of CMV disease. Prospective studies are required in order to identify the correlation between viremia and the need for treatment.

scholarly journals 1750. Epidemiology of Cytomegalovirus DNAemia in Pediatric Solid-Organ Transplant Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S641-S642
Author(s):  
Kristen Valencia Deray ◽  
Kathleen Hosek ◽  
Elizabeth A Moulton ◽  
Flor M Munoz ◽  
Flor M Munoz ◽  
...  
Keyword(s):  
High Risk ◽  
Solid Organ ◽  
Cmv Infection ◽  
Material Support ◽  
Kidney Recipients ◽  
Cmv Disease ◽  
Cmv Reactivation ◽  
Cmv Dnaemia ◽  
Cmv Status ◽  
Research Grant

Abstract Background Despite the widespread use of prevention strategies, CMV remains a common opportunistic infection in SOTR. Contemporary data regarding CMV in pediatric SOTR is limited. We sought to determine the frequency of and risk factors for CMV infection and disease in a large single-center cohort of pediatric SOTR. Methods A retrospective cohort study of patients <22 yr of age who received lung, heart, liver, kidney, or multi-organ transplants at TCH between 2014 and 2018 was completed. Universal CMV prophylaxis was used based on risk status (Figure 1). Primary outcome was CMV DNAemia (plasma level ≥ 1,000 IU/mL). Associations with CMV DNAemia were measured using Fisher exact, Kruskal–Wallis, and multivariate logistic regression. Survival analysis and time to CMV infection were assessed using Kaplan–Meier plots. Results Among 465 SOTR, 57 (12%) had CMV DNAemia ≥ 1,000 IU/mL; this included 9/52 (17%) lung, 22/155 (14%) liver, 16/125 (13%) heart, 1/9 (11%) multi-organ, and 9/124 (7%) kidney recipients. 6 (10%) SOTR had early-onset CMV reactivation while on antiviral prophylaxis. Post-prophylaxis, 48 (85%) SOTR had CMV reactivation and 3 (5%) had primary infection. Median time to DNAemia > 1,000 IU/mL was 366 days post-transplant for lung, 115 for liver, 185 for heart, and 290 for kidney (P = 0.04), reflecting differences in prophylaxis strategies. High-risk CMV status (D+/R- for heart, liver, kidney and D+ and/or R+ for lung) was associated with CMV DNAemia (P < 0.01, Figure 2). DNAemia was not associated with age at transplantation, type of organ, or induction immunosuppression. There was no difference in survival during the study follow-up period (1 – 5 years) for SOTR with vs. without DNAemia. Overall, 18/465 (4%) SOTR had CMV disease: 2 (4%) lung, 3 (2%) liver, 5 (4%) heart, 1 (11%) multi-organ, and 7 (6%) kidney recipients. 16 had CMV syndrome and 2 had tissue-invasive disease. Median (range) maximum viral loads were 35,768 IU/mL (3,239–4,807,992) for SOTR with vs. 2,605 IU/mL (1,000–112,000) for SOTR without CMV disease (P < 0.01) Conclusion This large contemporary cohort of pediatric SOTR on universal prophylaxis demonstrates low overall rates of CMV DNAemia and CMV disease. High-risk CMV status remains associated with CMV DNAemia, suggesting that further interventions targeting this group may be warranted. Disclosures Flor M. Munoz, MD, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.

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