An Investigator Initiated Prospective Randomized, Controlled Pilot Study in Order to Evaluate the Place of Valganciclovir in Prevention of Cytomegalovirus Reactivation Following Allogeneic Stem Cell Transplantation

Cytomegalovirus (CMV), the most common viral infection following stem cell transplantation (SCT), causes significant morbidity and mortality. It can result in CMV pneumonitis, hepatitis, encephalitis and gastrointestinal disease, as well as fever and neutropenia. Furthermore, CMV has been shown to be associated with a number of indirect effects in SCT recipients including reduced long-term patient survival, increased risks of opportunistic infections, allograft dysfunction, acute and chronic graft vs. host disease (GVHD). SCT patients at highest risk are seronegative donors, matched unrelated donors, SCT with T-cell depletion, patients after cord blood SCT, and patients with GVHD.

Valganciclovir, a valine ester pro-drug of ganciclovir, was developed to overcome the limitations of oral and i.v. ganciclovir, with a single once-daily 900 mg oral dose providing comparable plasma ganciclovir exposures to those achieved with 5 mg/kg i.v. ganciclovir. Its bioavailability is up to 10-fold higher than that of oral ganciclovir (same as above). There is already extensive clinical experience with valganciclovir in AIDS patients, where it has proved as effective as i.v. ganciclovir in treating newly diagnosed CMV retinitis, and in patients after solid organ transplant but no comparative data exists in patients after SCT.

We therefore planned a prospective, randomized study to evaluate the efficacy and safety of valganciclovir compared with acyclovir for prevention of CMV disease in SCT recipients.