Human cytomegalovirus (HCMV) infection in paediatric patients given allogeneic bone allogeneic bone marrow transplantation: role of early antiviral treatment for HCMV antigenaemaia on Patients' outcome

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Abstract
In a prospective study, we evaluated the role of early treatment with ganciclovir of human cytomegalovirus (HCMV) pp65-antigenaemia, as well as the risk factors related to the infection in 48 paediatric patients given an allogeneic bone marrow transplantation (BMT). HCMV infection occurred in 24 children, the overall actuarial risk of infection at 120 d being 51%. Development of acute graft-versus-host disease (GVHD), steroid therapy and serological status of both recipient and donor were the most powerful predictors of HCMV infection, none of the six seronegative patient/donor pairs developing HCMV infection. Considering only the seropositive recipients and patients given a seropositive marrow (42 cases), the actuarial risk of developing HCMV antigenaemia in patients with acute GVHD was 76% v 27% in those with or without GVHD (P < 0.005) and 79% v 15% respectively in patients who did or did not receive steroid therapy (P < 0.001). HCMV disease developed in 5/24 children with pp65-antigenaemia, which was detected before diagnosis in all cases but one. All patients with pp65-positive cells were treated with ganciclovir at a dose of 5 mg/kg twice daily for 14 d. In patients without acute GVHD no maintenance therapy was administered, whereas children with active acute GVHD were given additional therapy with ganciclovir at a dose of 5 mg/kg/d for 14 d. Ganciclovir produced complete clearing of viraemia and antigenaemia, with some patients presenting recurrences of antigenaemia, which were treated according to the above-mentioned schedule. Likewise, HCMV disease completely resolved after treatment with ganciclovir and no patients died from HCMV-related interstitial pneumonia. Our results suggest that an early short-term therapy with ganciclovir after demonstration of antigenaemia can be effective in reducing or abolishing HCMV-related mortality. This approach eliminates the use of ganciclovir in patients not presenting HCMV reactivation and therefore not benefiting from therapy. The administration of ganciclovir limited to the period needed to obtain antigenaemia clearance could also have the advantage of reducing myelotoxicity.

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