Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease

Abstract

Summary:Quantitative competitive PCR was used to monitor the quantity of cytomegalovirus (HCMV) in 1647 blood samples from 110 BMT recipients. DNAemia was detected in 49/110 (45%) of the patients, of whom 15/49 experienced HCMV disease. Peak virus load during surveillance was elevated in symptomatic (median 4.5 log 10 genomes/ml) vs asymptomatic patients (median 3.6 log 10 genomes/ml, P = 0.002) and was also significantly elevated in HCMV seropositive recipients of seronegative marrow, (R+D−, median 5.0 log 10 ), compared to those in the R−D− and R+D+ groups (P Ͻ 0.01 and Ͻ0.005). Odds ratios for disease per 0.25 log 10 increase in viral load, recipient seropositivity and aGVHD were 1.43 (P = 0.004), 6.60 (P = 0.05) and 3.17 (P = 0.08), respectively. In multivariate logistic regression analysis only elevated viral load remained a significant risk factor for HCMV disease. The computed disease probability viral load curve showed a rapid increase in disease risk at viral loads between 3.8 and 5.5 log 10 genomes/ml in blood, and odds ratios for disease were determined for different threshold viral loads. These data demonstrate the central role of viral load in the pathogenesis of HCMV in BMT recipients and provide an additional marker for targeting and monitoring therapy.

Dose-adjusted preemptive therapy for cytomegalovirus disease based on real-time polymerase chain reaction after allogeneic hematopoietic stem cell transplantation

“…[20][21][22] Numerous publications have shown the use of a variety of molecular amplification methods. [23][24][25][26][27][28] In our previous report, we retrospectively demonstrated that quantitative real-time PCR was more sensitive and correlated with the effects of antiviral treatment better than CMV antigenemia in a small number of patients with CMV gastroenteritis. 13 In this prospective study with more patients, we confirmed our previous observation and that real-time PCR-guided preemptive therapy more effectively but not completely prevented the occurrence of CMV diseases.…”

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

“…Similar conclusions have been drawn from recent studies involving other immunosuppressed cohorts. 38,[42][43][44][45][46][47][48][49][50] Quantitative PCR for CMV appears to be an effective diagnostic tool in identifying patients with disease. In addition, PCR detection of DNA targets is less sensitive to sample handling than other diagnostic tests.…”

Modelling cytomegalovirus replication patterns in the human host: factors important for pathogenesis

“…The patients compromised renal transplant (nZ12) (Hassan Walker et al 1999), liver transplant (nZ18) (Cope et al 1997) and bone marrow transplant (nZ13) (Gor et al 1998) recipients and 16 HIV-infected individuals (Bowen et al 1997). HCMV diseases conformed to the International Workshop definition (Ljungman et al 2002) and included HCMV retinitis (nZ17), gastrointestinal disease (nZ7), hepatitis (nZ4), pyrexial debilitating disease (nZ14) and HCMV pneumonitis (nZ14).…”

“…These studies have shown that viral load is a dominant risk factor for HCMV disease (Cope et al 1997;Gor et al 1998;Spector et al 1998;Emery et al 1999a,b;Hassan-Walker et al 1999;Limaye et al 2001). In addition, kinetics of replication during the early phases of active replication have been defined and used to estimate the basic reproductive number of HCMV (Emery et al 2002) and to provide prognostic information in the immunocompromised host (Emery et al 2000;Schafer et al 2001).…”