We evaluated the efficacy, toxicity, and outcome of preemptive ganciclovir
(GCV) therapy in 80 cytomegalovirus (CMV)-seropositive patients
allografted between 1991 and 1996 and compared their outcome to 35
seronegative patients allografted during the same period. Both cohorts
were comparable with respect to diagnosis and distribution of high- versus
standard-risk patients. All patients received a stem cell graft from an
HLA-identical sibling donor, and grafts were partially depleted of T cells
in 109 patients. Patients were monitored for CMV antigenemia by leukocyte
expression of the CMV-pp65 antigen. Fifty-two periods of CMV reactivation
occurring in 30 patients were treated preemptively with GCV. A favorable
response was observed in 48 of 50 periods, and only 2 patients developed
CMV disease: 1 with esophagitis and 1 with pneumonia. Ten of 30 treated
patients developed GCV-related neutropenia (less than 0.5 x 10(9)/L),
which was associated with a high bilirubin at the start of GCV therapy.
Overall survival at 5 years was 64% in the CMV-seronegative cohort and 40%
in the CMV-seropositive cohort (P =.01). Increased treatment-related
mortality accounted for inferior survival. CMV seropositivity proved an
independent risk factor for developing acute graft-versus-host disease,
and acute graft-versus-host disease predicted for higher treatment-related
mortality and worse overall survival in a time-dependent analysis. We
conclude that, although CMV disease can effectively be prevented by
preemptive GCV therapy, CMV seropositivity remains a strong adverse risk
factor for survival following partial T-cell-depleted allogeneic stem cell
transplantation