Summary:Herpes simplex virus (HSV) causes serious problems in immuno-compromised patients such as those receiving a bone marrow transplant (BMT) for a hematological malignancy. Resistance to acyclovir (ACV) is a growing major concern. Foscarnet is a non-thymidine kinasedependent agent, but the emergence of ACV and foscarnet-resistant HSV requires a new therapeutic approach. We describe a girl treated with cidofovir for a lifethreatening ACV-resistant HSV infection after an unrelated BMT for a relapse of an acute myeloblastic leukemia (AML). Bone Marrow Transplantation (2000) 26, 903-905. Keywords: AML; bone marrow transplantation; herpes simplex virus infection; cidofovir Herpes simplex virus (HSV) infection is the most common viral infection after bone marrow transplant (BMT). 1 Acyclovir (ACV) is the drug of choice for prophylactic and curative treatment of HSV infection. 2 However, the emergence of ACV-resistant HSV infection is a new and challenging problem. Foscarnet is usually effective in this situation. Cross-resistance to ACV and foscarnet has been previously described in patients after BMT. 2,3 Cidofovir has been recently approved for the treatment of CMV retinitis in acquired immuno-deficiency syndromes. It is the first of a new class of nucleotide antiviral agents with activity against a broad spectrum of herpes viruses. 4 Here, we report, successful treatment of an ACV and foscarnet cross-resistant herpetic infection with cidofovir in a child after an unrelated BMT. Case reportAn 18-month-old girl, was admitted in June 1998 with AML 4 with a t(9;11)(p12;q23). A complete remission was During the neutropenic period following induction chemotherapy, the patient developed a severe mucositis which was slowly but successfully treated with ACV 10 mg/m 2 every 8 h.The two subsequent courses of consolidation were complicated with the same HSV mucositis. No investigations were performed to study the HSV sensitivity to antiviral treatment because of the good prior response to ACV.After a conditioning regimen including busulfan 120 mg/m 2 /day p.o. in divided doses daily for 4 days (TD: 480 mg/m 2 ), cyclophosphamide 50 mg/kg/day once daily i.v. for 4 days (TD: 200 mg/kg) and anti-lymphocyte serum 5 mg/kg (TD: 20 mg/kg), the patient was transplanted with bone marrow from of an unrelated HLA matched donor. To prevent graft-versus-host-disease (GVHD) she received i.v. cyclosporin (2 mg/kg/day) and methotrexate (15 mg/m 2 day 1 then 10 mg/m 2 on days 3, 6, and 11).Before initiation of the BMT procedure, blood PCR assay for HSV was negative.At day +5 after bone marrow infusion, a recurrence of HSV mucositis occurred despite prophylaxis with ACV (250 mg/m 2 every 8 h). After a transient improvement related to the end of aplasia (day +15) the HSV lesions extended to the right cheek, the larynx and the nose. The evolution was complicated by a subsequent failure of BMT. Only activated lymphocytes were observed on the bone marrow smears, without viral particles. The lesions became necrotic (Figure 1). At day +70, a life...
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