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

To determine the risk factors and outcomes associated with rising cytomegal ovirus (CMV) antigenemia levels during preemptive therapy among stem cell a llograft recipients, 119 patients with CMV antigenemia were studied. Patien ts were prospectively monitored for CMV antigenemia weekly; those with posi tive findings on antigenemia tests were treated with intravenous ganciclovi r (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 w ere 2 or more times greater than their baseline values, whereas 33 of 119 ( 28%) patients demonstrated increases that were 5 or more times greater. Ris ing antigenemia was confirmed by polymerase chain reaction for CMV DNA. Mul tivariate analysis identified corticosteroids as the primary risk factor fo r 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 mglkg 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 pat ients in whom CMV disease developed during therapy, however, had rising ant igenemia levels. Among the 47 patients with antigenemia increases greater t han or equal to twice the baseline, 15 were re-induced with antivirals, whe reas 32 continued to receive maintenance therapy. All 4 patients in whom CM V disease developed during therapy received maintenance therapy, and 3 died with CMV disease. Thus, host factors such as the receipt of corticosteroid s explain increasing viral load during the early phase of preemptive therap y. Continued induction dosing or re-induction may protect against early bre akthrough CMV disease and CMV-related death among patients with rising anti genemia on preemptive therapy. (C) 2001 by The American Society of Hematolo gy.