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  • Original Article
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Viral Infections

Randomized clinical trial of ganciclovir vs acyclovir for prevention of cytomegalovirus antigenemia after allogeneic transplantation

Abstract

Cytomegalovirus (CMV) disease remains a major cause of morbidity following allogeneic stem cell transplantation (SCT). In a prospective randomized trial, we tested prophylactic therapy with ganciclovir or acyclovir for patients at high risk of disease. Ninety-one CMV seropositive recipients of related (n = 53) and unrelated (n = 38) donor transplants were enrolled. All patients received intravenous (i.v.) ganciclovir 5 mg/kg every 12 h days −7 to −2, followed by acyclovir 10 mg/kg i.v. every 8 h from day −1 until neutrophil engraftment. Patients were then randomly assigned to either ganciclovir (n = 45) or acyclovir (n = 46) until day 100 post transplant. Any degree of antigenemia was treated with ganciclovir 5 mg/kg i.v. twice a day for 2 weeks, followed by 5 mg/kg i.v. each weekday for 6 weeks. At day 100, the cumulative incidence of antigenemia was 31% (95% CI 17–45%) for ganciclovir and 41% (95% CI 26–56%) (P = 0.22) for acyclovir prophylaxis, respectively. The assigned prophylaxis cohort did not predict for CMV antigenemia. The cumulative incidence of CMV disease at 12 months was 13% (95% CI 3–23%) and 17% (95% CI 6–28%) (P = 0.59) for the ganciclovir- and acyclovir-treated groups, respectively. An absolute neutrophil count (ANC) 1500 × 106/l at randomization (P < 0.01) and grade II–IV acute graft-versus-host-disease (P = 0.01), but not the assigned prophylaxis cohort (P = 0.62), were independent risk factors for CMV disease. The incidence of fungal infections and renal insufficiency was similar across treatment groups; however, bacterial infections and secondary neutropenia occurred more frequently in the ganciclovir group. With our study powered to detect a 60% reduction in antigenemia with ganciclovir prophylaxis, we did not find a statistically significant difference between ganciclovir and acyclovir when used as part of an overall strategy for prevention of CMV antigenemia and disease in SCT, although fewer side-effects occurred with acyclovir treatment.

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Burns, L., Miller, W., Kandaswamy, C. et al. Randomized clinical trial of ganciclovir vs acyclovir for prevention of cytomegalovirus antigenemia after allogeneic transplantation. Bone Marrow Transplant 30, 945–951 (2002). https://doi.org/10.1038/sj.bmt.1703770

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