The main risk factors for cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants (SCT) are recipient CMV seropositivity and acute
graft-versus-host disease. Currently, two
antiviral strategies, prophylactic or preemptive
antiviral treatment, are used for prevention of CMV disease. Preemptive treatment is most favorable when short-term (14-day) treatment is applied. Several methods are available for monitoring of CMV reactivation. PCR-based CMV
DNA detection assays are the most sensitive methods; however, the clinical benefit of this high sensitivity is unclear. Even more, there is lack of clarity whether PCR tests can better be performed with plasma, whole blood, or peripheral blood leukocyte samples. Recovery of a CMV-specific CD8(+) cytotoxic-T-lymphocyte (CTL) response is necessary for preventing CMV reactivation and disease. Reconstitution of absolute CMV-specific CTL counts to values above 10 x 10(6) to 20 x 10(6) CTLs/liter is associated with protection from CMV disease. In the near future, preemptive
therapy might be withheld in patients with CMV reactivation who are shown to have adequate CMV-specific cytotoxic T-cell levels.
Antiviral therapy with (val)
acyclovir has been studied only as prophylactic treatment for prevention of CMV
infection. High-dose oral
valacyclovir is more effective than
acyclovir when used in addition to preemptive treatment of CMV reactivation with
ganciclovir or
foscarnet. Three
antiviral drugs have been tested for preemptive
therapy of CMV reactivation and/or treatment of CMV disease. Although intravenous
ganciclovir is considered the drug of choice,
foscarnet has similar efficacy and less toxicity, especially hematologic toxicity.
Cidofovir has not been tested extensively, but so far the results are disappointing. Oral
valganciclovir for preemptive treatment of SCT recipients is currently being studied. In addition to
antiviral therapy, adoptive immunotherapy with CMV-specific cytotoxic T cells as prophylactic or preemptive
therapy is a very elegant strategy; however, generation of these cells is expensive and time-consuming, and therefore the
therapy is not available at every
transplantation center. Magnetic selection of CMV-specific CD8(+) T cells from peripheral blood by using HLA class I-
peptide tetramers may be very promising, making this strategy more accessible.