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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2240-2245
Increased transplant-related morbidity and mortality in
CMV-seropositive patients despite highly effective prevention of CMV
disease after allogeneic T-cell-depleted stem cell transplantation
Annoek E. C. Broers,
Ron van der Holt,
Joost
W. J. van Esser,
Jan-Willem Gratama,
Sonja Henzen-Logmans,
Vibeke Kuenen-Boumeester,
Bob Löwenberg, and
Jan J. Cornelissen
From the Department of Hematology, Department of Statistics,
Department of Immunology, and Department of Pathology, University
Hospital Rotterdam/Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
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 × 109/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.
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