This project addresses the two major infectious causes of morbidity and mortality after hematopoietic stem cell transplantation, specifically cytomegalovirus (CMV) and fungal infections. Studies addressing CMV will focus on pharmocologic approaches to prevention of CMV disease including pharmacokinetic targeting of ganciclovir aimed at reducing GCV-related neutropenia and testing long-term maintenance antiviral chemotherapy using cidofovir. Fungal infections, primarily Candida and Aspergillus, have emerged as the leading infectious cause of death after marrow transplantation, in part because of lack of sensitive diagnostic markers which allow identification at early stages of infection. Studies addressing fungal infections include the development of novel polymerase chain reaction and antigen-based detection assays, and their prospective evaluation using clinical samples from patients with defined Candida and Aspergillus infections. New strategies for treatment of invasive Aspergillus infection, including evaluation of a new triazole (voriconazole) with excellent activity against Aspergillus, as well as the use of granulocyte transfusions for infected neutropenic patients, will be evaluated. The ultimate goal is to use early detection markers to design preemptive antifungal therapy. These studies will be important in reducing morbidity and mortality from CMV and invasive Aspergillus infection, the two leading causes of infectious death during the first year after transplant.
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