Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes

Abstract

To determine the risk factors and outcomes associated with rising cytomegalovirus (CMV) antigenemia levels during preemptive therapy among stem cell allograft recipients, 119 patients with CMV antigenemia were studied. Patients were prospectively monitored for CMV antigenemia weekly; those with positive findings on antigenemia tests were treated with intravenous ganciclovir (5 mg/kg twice daily for 1 week, followed by 5 mg/kg per day for 5-6 d/wk). While on therapy, 47 of 119 (39%) patients demonstrated increases that were 2 or more times greater than their baseline values, whereas 33 of 119 (28%) patients demonstrated increases that were 5 or more times greater. Rising antigenemia was confirmed by polymerase chain reaction for CMV DNA. Multivariate analysis identified corticosteroids as the primary risk factor for increasing antigenemia: for increases greater than or equal to twice the baseline, 1 to 2 mg/kg steroids was associated with an odds ratio (OR) of 4.0. For increases greater than or equal to 2 mg/kg steroids, the OR was 10.1. CMV isolates obtained at the time of rising antigenemia were susceptible to ganciclovir, indicating that resistance was not a major factor. Overall, rising antigenemia levels were not correlated with CMV disease. All 4 patients in whom CMV disease developed during therapy, however, had rising antigenemia levels. Among the 47 patients with antigenemia increases greater than or equal to twice the baseline, 15 were re-induced with antivirals, whereas 32 continued to receive maintenance therapy. All 4 patients in whom CMV disease developed during therapy received maintenance therapy, and 3 died with CMV disease. Thus, host factors such as the receipt of corticosteroids explain increasing viral load during the early phase of preemptive therapy. Continued induction dosing or re-induction may protect against early breakthrough CMV disease and CMV-related death among patients with rising antigenemia on preemptive therapy. (Blood. 2001;97:867-874)

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

“…In addition to ganciclovir therapy, intensive immunosuppressive therapy including high-dose steroids and ATG could be a risk factor for recurrent CMV infection and subsequent late CMV diseases due to delaying CMV-specific immune reconstitution. 34,35 To totally evaluate the efficacy and disadvantages of a reduced dose of ganciclovir, a comparative study should be performed.…”

Real-time PCR assays based on distinct genomic regions for cytomegalovirus reactivation following hematopoietic stem cell transplantation

“…[3][4][5] However, some unsolved problems remain, not least that the procedure remains unstandardized. Whereas antigenemia assays have been almost completely standardized using an anti-pp65 antibody, 6,7 real-time PCR assays have been carried out using a variety of procedures: the target region being amplified by real-time PCR assay differs in each report, some target the immediate early protein (IE), while others target glycoprotein B (gB) or the US17 region, 2,4,8 and primers and probes for the target region also differ. 2,9,10 Few reports have been published which compare the viral load detected by real-time PCR assay targeting distinct genomic regions.…”

Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation

“…8 In this study, rising antigenemia was defined as the observation of an increase in the antigenemia level to more than double that of the baseline after GCV 10 mg/kg/day for more than 7 days. In our subjects, 25 episodes of rising antigenemia occurred in 22 patients.…”