Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of Cytomegalovirus disease after hematopoietic cell transplantation

Abstract

Cytomegalovirus (CMV) surveillance and preemptive therapy (PET) is the most commonly used strategy for CMV disease prevention in hematopoietic cell transplant (HCT) recipients. In 2007, we introduced a CMV prevention strategy for those patients at risk for CMV disease using quantitative PCR surveillance, with treatment thresholds determined by patient risk factors. Patients (N=384) received PET either at a plasma viral load of ≥500 copies/ml, at ≥100 copies/ml if receiving ≥ 1 mg/kg of prednisone or anti-T cell therapies, or if a ≥ 5-fold viral load increase from baseline was detected. Compared to patients prior to 2007 undergoing antigenemia-based surveillance (n=690) with PET initiated for any positive level, the risk-adapted PCR based strategy resulted in similar use of antiviral agents, and similar risks of CMV disease, toxicity and non-relapse mortality (NRM) in multivariable models. The cumulative incidence of CMV disease by day 100 was 5.2% in the PCR group compared to 5.8% in the antigenemia group (1 year: 9.1% PCR vs 9.6% antigenemia). Breakthrough CMV disease in the PCR group was predominantly in the gastrointestinal (GI) tract (16/20 cases, 80%). However, unlike CMV pneumonia, CMV GI disease was not associated with increased NRM (adjusted hazard ratio 1.13, P=0.8 [GI disease] vs. 8.41, P<0.001 [pneumonia]). Additionally, in this contemporary cohort CMV seropositivity in the donor or recipient was not associated with NRM at 1 year. Thus, the transition to a PET strategy based on CMV viral load and host risk factors successfully prevented CMV disease without increasing the proportion of patients receiving PET and attributable toxicity. Breakthrough disease in PCR-based PET occurs at a low incidence and presents primarily as GI disease which is more likely to be responsive to antiviral therapy.