Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneicT-cell-depleted stem cell transplantation

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 patient s allografted during the same period. Both cohorts were comparable with res pect 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 w ere monitored for CMV antigenemia by leukocyte expression of the CMV-pp65 a ntigen. 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 a nd I with pneumonia. Ten of 30 treated patients developed GCV-related neutr openia (less than 0.5 x 10(9)/L), which was associated with a high bilirubi n at the start of GCV therapy. Overall survival at 5 years was 64% in the C MV-seronegative cohort and 40% in the CMV-seropositive cohort (P=.01). Incr eased treatment-related mortality accounted for inferior survival. CMV sero positivity proved an Independent risk factor for developing acute graft-ver sus-host disease, and acute graft-versus-host disease predicted for higher treatment-related mortality and worse overall survival On a time-dependent analysis, We conclude that, although CMV disease can effectively be prevent ed by preemptive GCV therapy, CMV seropositivity remains a strong adverse r isk factor for survival following partial T-cell-depleted allogeneic stem c ell transplantation. (Blood, 2000; 95:2240-2245) (C) 2000 by The American S ociety of Hematology.