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