Cytomegalovirus Treatment in Pediatric Hematopoietic Stem Cell Transplant Patients

Wattles, Bethany A.; Kim, Abby J.; Lucas, Kenneth G.; Elder, Joshua J.

doi:10.1097/mph.0000000000000730

Cited by 14 publications

(13 citation statements)

References 68 publications

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“…The absence of commutable International Standards (IS) prevented for many years the establishment of clinical thresholds for therapeutic decisions due to the high variability observed between the different techniques or matrix used for the viral loads determination and to the absence of harmonization of these tests (Caliendo et al, 2009;Wolff et al, 2009). EBV (Fryer et al, 2016b) and CMV (Fryer et al, 2016a) WHO International Standards were developed to meet the needs expressed in this way in the guidelines and the recommendations made by the healthcare professionals (Andrews et al, 2011;Gulley and Tang, 2010;Heemann et al, 2011;Kim et al, 2017;Kotton et al, 2013;Navarro et al, 2017;Torre-Cisneros et al, 2016;Wattles et al, 2017). However, the commutability of the EBV (Abeynayake et al, 2014;Ruf and Wagner, 2013;Tang et al, 2016) and CMV (Fryer et al, 2016c;Hayden et al, 2015Hayden et al, , 2013 WHO IS was examined and questioned.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Abbott RealTime quantitative CMV and EBV assays using the maxCycle protocol in a laboratory automation context

Bontems

Boreux

Capraro

et al. 2019

Journal of Virological Methods

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Real-time PCR are often used for the diagnosis and monitoring of Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections in susceptible populations. In this context, we evaluated the analytical performances of the Abbott RealTime CMV/EBV maxCycle protocol automated on the m2000 platform (Abbott). It was compared to our routinely-used procedure consisting of a NucleoMag® DNA extraction automated on a STARlet platform followed by manually processed CMV and EBV quantitative real-time PCR (Diagenode). In this study, we showed that both EBV assays exhibited a similar sensitivity but with a better precision for the EBV Abbott RealTime assay. For the CMV performances, the Abbott assay was more sensitive and more precise than our routine method. The use of WHO International Standards also indicated a slight underestimation of the viral loads (−0.25 log 10 IU/mL and −0.21 log 10 IU/mL for CMV and EBV assays respectively) while these were rather overestimated with the Starlet/Diagenode method (0.48 log 10 IU/mL and 0.19 log 10 IU/mL for CMV and EBV assays respectively). These trends were confirmed using relevant whole-blood clinical samples and external quality controls. The workflows were also compared and we highlighted a significant technician hands-on time reduction (−63%) using the Abbott CMV/EBV maxCycle automated protocol.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Abbott RealTime quantitative CMV and EBV assays using the maxCycle protocol in a laboratory automation context

Bontems

Boreux

Capraro

et al. 2019

Journal of Virological Methods

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“…CMV disease was defined by the presence of signs and/or symptoms of end-organ disease along with CMV detection in related fluid or tissue samples. [6] All cord blood units were considered seronegative. Monitoring was initiated after neutrophil engraftment using CMV antigenemia or plasma-based PCR assay and continued through day 100 posttransplant.…”

Section: Methodsmentioning

confidence: 99%

Factors associated with cytomegalovirus infection in children undergoing allogeneic hematopoietic stem-cell transplantation

et al. 2019

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While preemptive therapy with ganciclovir (GCV) for cytomegalovirus (CMV) infection is used following allogeneic hematopoietic stem-cell transplantation (HSCT), risk factors for CMV infection in children undergoing HSCT are poorly understood.We studied CMV reactivation following allogeneic HSCT by retrospectively analyzing pediatric patients who received allogeneic HSCT and preemptive GCV therapy between 1998 and 2016. The level of viremia requiring preemptive GCV therapy was >1 CMV antigen-positive cells per 5 × 105 leukocytes during the antigenemia assay era and >1000 copies/mL in the polymerase chain reaction era. Among 290 at-risk patients, 54 (18.6%) patients had primary CMV infection or CMV reactivation occurring at a median of 76 days (range, 7–234) following HSCT. CMV reactivation occurred in 28.2% (44/156) of CMV-seropositive transplant recipients at a median of 26 days posttransplant.Univariate and multivariate analyses revealed statistically significant relationships between CMV infection and grade III–IV acute graft-vs-host disease, seronegative donor/seropositive recipient combination, and unrelated/mismatched donors. The remaining demographic factors were not predictive of CMV infection.The seronegative donor/seropositive recipient combination for HSCT was associated with an incomplete response to antiviral therapy. Human leukocyte antigen identical donors were the best choice for patients undergoing allogeneic HSCT to reduce the incidence of CMV disease and mortality.

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“…Cytomegalovirus (CMV) infection remains one of the most devastating viral infections in recipients of hematopoietic stem cell transplantation (HSCT) [ 1 ]. Compared to adult patients, pediatric patients reportedly have higher risks of developing post-transplant CMV infections [ 2 , 3 ]. Although end-organ diseases caused by CMV infection after HSCT are rare, CMV infections are associated with higher mortality, increased risks of developing complications at affected sites, and life-threatening infections with other pathogens [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Currently, there are no standard guidelines for the prevention of CMV infection in pediatric recipients of HSCT. Antiviral drugs might be used as prophylactic, preemptive, or therapeutic strategies [ 2 , 6 ]. However, the prolonged and repeated administration of antiviral drugs could cause resistance to these drugs, thereby resulting in treatment failure [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus Infection and the Implications of Drug-Resistant Mutations in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Retrospective Study from a Tertiary Hospital in China

Wang

et al. 2021

Infect Dis Ther

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Introduction Drug-resistant cytomegalovirus (CMV) infection remains a challenge in the management of pediatric recipients of hematopoietic stem cell transplantation (HSCT). In this study, we retrospectively reviewed the clinical data on pediatric recipients of HSCT and identified known and unknown drug-resistant CMV variants. Methods A total of 221 children underwent allogeneic HSCT between October 2017 and November 2019 at Shenzhen Children’s Hospital; of these, 35 patients were suspected of having drug-resistant CMV infections and were tested for drug-resistant mutations in the UL97 and UL54 genes by Sanger sequencing. Results Mutations in UL97 or UL54 , or in both, were detected in 11 patients. Most of these mutations have not been previously reported. The UL97 mutation (A582V) was detected in only one patient who also harbored two UL54 mutations (T760X and R876W). One patient with both the G604S and T691A mutations in the UL54 gene died of CMV pneumonia. We investigated the risk factors associated with the development of drug-resistant CMV infection. Patients in whom both the donor and recipient had positive CMV serostatuses were less likely to have drug-resistant mutations (Fisher’s exact test, p < 0.05). Conclusion Newly and previously detected CMV mutations in UL97 and UL54 may be associated with the development of drug-resistant CMV infection. The detection of these mutations may provide guidance for the management of post-transplant CMV infections. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00452-4.

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Cytomegalovirus Treatment in Pediatric Hematopoietic Stem Cell Transplant Patients

Cited by 14 publications

References 68 publications

Evaluation of the Abbott RealTime quantitative CMV and EBV assays using the maxCycle protocol in a laboratory automation context

Evaluation of the Abbott RealTime quantitative CMV and EBV assays using the maxCycle protocol in a laboratory automation context

Factors associated with cytomegalovirus infection in children undergoing allogeneic hematopoietic stem-cell transplantation

Cytomegalovirus Infection and the Implications of Drug-Resistant Mutations in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Retrospective Study from a Tertiary Hospital in China

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