Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor): search for optimal cutoff value by real-time PCR

Abstract

BackgroundHuman cytomegalovirus (CMV) infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications.MethodsDuring the first 150 days after allogeneic HSTC, thirty patients were monitored weekly for active CMV infection by pp65 antigenemia, nested-PCR and real-time PCR assays. Receiver operating characteristic (ROC) plot analysis was performed to determine a threshold value of the CMV DNA load by real-time PCR.ResultsUsing ROC curves, the optimal cutoff value by real-time PCR was 418.4 copies/104 PBL (sensitivity, 71.4%; specificity, 89.7%). Twenty seven (90%) of the 30 analyzed patients had active CMV infection and two (6.7%) developed CMV disease. Eleven (40.7%) of these 27 patients had acute GVHD, 18 (66.7%) had opportunistic infection, 5 (18.5%) had chronic rejection and 11 (40.7%) died - one died of CMV disease associated with GVHD and bacterial infection.ConclusionsThe low incidence of CMV disease in HSCT recipients in our study attests to the efficacy of CMV surveillance based on clinical routine assay. The quantification of CMV DNA load using real-time PCR appears to be applicable to the clinical practice and an optimal cutoff value for guiding timely preemptive therapy should be clinically validated in future studies.

Cytomegalovirus Infection in Pediatric Allogenic Hematopoietic Stem Cell Transplantation. A Single Center Experience

“…In a study discussing the clinical utility of CMV realtime PCR in HSCT recipients, the cut-off value for preemptive therapy was determined to be approximately between 2 × 10 4 copies/mL (sensitivity, 80.0%; specificity, 50.0%) and 3 × 10 4 copies/mL (sensitivity, 90.0%; specificity, 70.0%) [27]. However, the optimal cut-off value for the initiation of preemptive therapy remains to be determined [28]. In our study, the onset of CMV infection was always before D+100, emphasizing its role in early post-transplant morbidity.…”

Determination, validation and standardization of a CMV DNA cut-off value in plasma for preemptive treatment of CMV infection in solid organ transplant recipients at lower risk for CMV infection

“…[7][8][9][10][11][12][13] The clinical utility of real-time PCR tests to guide preemptive therapy in transplant recipients at high-risk for CMV infection has been mainly studied in hematopoietic stem cell transplant recipients (HSCTR) and in SOT recipients (SOTR) at highrisk. [14][15][16][17][18] Surprisingly, some studies have shown a higher incidence of CMV disease in SOTR at low-risk of CMV. [19][20][21][22] In addition, results showed significant differences between different techniques used to determine the CMV viral load and therefore results cannot be compared.…”

Cytomegalovirus load at treatment initiation is predictive of time to resolution of viremia and duration of therapy in hematopoietic cell transplant recipients

“…Despite the widespread use of quantitative PCR, there is no consensus regarding the CMV level at which preemptive therapy should be initiated(9-11). Some studies have suggested a threshold of 500 copies/mL, others 1000 copies/mL, while others suggest different thresholds dependent on recipient risk(12-15). This lack of consensus translates into significant heterogeneity in clinical practice.…”