title: Monitoring of cytomegalovirus viral loads by two molecular assays in whole-blood and plasma samples from hematopoietic stem cell transplant recipients.
abstract: Cytomegalovirus (CMV) viral loads in hematopoietic stem cell transplant (HSCT) recipients are typically monitored using quantitative molecular assays. The Roche Cobas AmpliPrep/Cobas TaqMan CMV test (Cobas CMV) has recently been cleared by the FDA for the monitoring of CMV viral loads in plasma samples from transplant patients. In this study, we compare and correlate the viral loads obtained by a laboratory-developed test (LC CMV) (using Roche analyte-specific reagents [ASR] on the LightCycler 2.0) on whole-blood specimens with those obtained on corresponding plasma and whole-blood specimens by the Cobas CMV assay. Testing was performed on 773 archived patient specimens. The strength of the agreement was good for the two assays performed on whole blood (κ=0.6; 95% confidence interval [CI], 0.51 to 0.7) and moderate when the tests were performed on different sample types (κ=0.54; 95% CI, 0.47 to 0.62 for the LC CMV whole blood [WB] assay versus Cobas plasma [PL], and κ=0.57; 95% CI, 0.5 to 0.65 for the Cobas WB assay versus Cobas PL), although the difference was not statistically significant. Using a combination gold standard (i.e., a true positive was a specimen that was positive by two or more methods), the sensitivity and specificity of the assays were 78.8% and 99.3% for the LC CMV assay, 85.2% and 98.1% for the Cobas CMV WB assay, and 100% and 90.5% for Cobas CMV PL assay, respectively. A comparison of the CMV viral load trends in both plasma and whole blood from a few patients with multiple positive successive samples showed similar slopes, with differences in the slope ranging from 0.01 to 0.22. However, the absolute value for individual viral load differed markedly with whole-blood viral loads, being on average 0.5- to 1.22-log higher than those in plasma. The Cobas CMV assay provides a valid option for the monitoring of viral loads in transplant patients. Due to its increased sensitivity, the detection of CMV DNA in patients with low viral loads (i.e., those below limit of quantification [LOQ]) is increased with the Cobas CMV assay in plasma specimens. Longitudinal prospective studies will be needed to examine the clinical significance of these low-level viral loads.
authors: Department of Laboratory Medicine, Microbiology Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA babadyn@mskcc.org.
authors: N Esther
authors: http://orcid.org/0000-0003-4399-1249
authors: NE
authors: Babady
authors: Department of Laboratory Medicine, Microbiology Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: Cindy
authors: C
authors: Cheng
authors: Department of Laboratory Medicine, Microbiology Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: Evelyn
authors: E
authors: Cumberbatch
authors: Department of Laboratory Medicine, Microbiology Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: Jeffrey
authors: J
authors: Stiles
authors: Department of Medicine, Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: Genovefa
authors: G
authors: Papanicolaou
authors: Department of Laboratory Medicine, Microbiology Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA Department of Medicine, Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: Yi-Wei
authors: http://orcid.org/0000-0003-4888-6771
authors: YW
authors: Tang
mesh_terms: D001769:Blood / Q000821:virology*; D003586:Cytomegalovirus Infections / Q000821:virology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016867:Immunocompromised Host; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D012680:Sensitivity and Specificity; D019562:Viral Load / Q000379:methods*
references: Expert Opin Biol Ther. 2009 Apr;9(4):383-5
references: 19344277
references: J Mol Diagn. 2009 Mar;11(2):87-92
references: 19225134
references: J Clin Microbiol. 2011 Aug;49(8):3044-6
references: 21653778
references: J Clin Virol. 2011 Nov;52(3):222-4
references: 21900039
references: Hematology Am Soc Hematol Educ Program. 2011;2011:305-9
references: 22160050
references: Clin Infect Dis. 2012 Jun;54(12):1793-7
references: 22412060
references: Clin Infect Dis. 2013 Feb;56(3):367-73
references: 23097587
references: Clin Infect Dis. 2013 Feb;56(3):374-5
references: 23097589
references: Diagn Microbiol Infect Dis. 2013 Apr;75(4):440-2
references: 23428458
references: Expert Rev Anti Infect Ther. 2014 Feb;12(2):193-210
references: 24341395
references: J Clin Microbiol. 2014 May;52(5):1711-3
references: 24554746
references: Leuk Lymphoma. 2015 Jun;56(6):1799-805
references: 25224458
references: J Clin Microbiol. 2003 Jan;41(1):187-91
references: 12517846
references: J Clin Microbiol. 2007 Jun;45(6):1972-3
references: 17314226
references: Diagn Mol Pathol. 2008 Sep;17(3):166-73
references: 18382366
references: Am J Transplant. 2009 Feb;9(2):258-68
references: 19178413
references: Transplantation. 2011 Jan 27;91(2):231-6
references: 21048530