Cytomegalovirus prophylaxis and treatment following bone marrow transplantation

OBJECTIVE: To provide an overview of the role of cytomegalovirus (CMV) in the bone marrow transplant (BMT) population and update the current methods of prevention and treatment of CMV infection and disease, with emphasis on CMV interstitial pneumonia (CMV-IP). DATA SOURCES: The current medical literature, including abstracts presented at recent national and international meetings, is reviewed. References were identified by searching the MEDLINE database from January 1988 through June 1994. The reference lists of the published studies and reviews obtained from the initial literature search were reviewed as well. STUDY SELECTION: Data regarding the epidemiology of CMV, the risk factor associated with CMV infection and disease, as well as data on the prevention and the treatment of CMV infection and disease in the BMT population are cited. Specific attention was focused on randomized, placebo-controlled studies pertaining to the prevention of CMV infection and disease in CMV-immunoglobulin G positive recipients undergoing allogeneic BMT. Information from nonrandomized, placebo-controlled studies was included in the absence of stronger data. DATA EXTRACTION: Information contributing to CMV in the BMT population was reviewed. Data supporting and disputing specific preventive and treatment modalities are presented. DATA SYNTHESIS: The incidence of CMV seropositivity in the general population is high and while BMT becomes a widely accepted treatment modality, CMV reactivation and subsequent disease, especially CMV-IP, becomes a significant prognostic factor of morbidity and mortality. Even though antiviral agents such as ganciclovir and foscarnet can inhibit the viral replication in vivo, they have not been able to treat CMV-IP effectively. It has been suggested that CMV-IP is an immunopathologic process that can cause irreversible damage, hence, the low efficacy of antiviral therapy and the associated high mortality. Immunomodulating agents such as intravenous immune globulin and cytomegalovirus hyperimmune globulin can increase the efficacy of antivirals in the treatment of CMV-IP. This further supports the postulated immunopathologic process of this disease. The lack of understanding of the pathophysiology of the disease compromised the efforts of treatment and led to the development of preventive interventions with antiviral and immunomodulatory regimens that resulted in a significantly lower incidence of infection and disease. As a result of current data, the Eastern Cooperative Oncology Group has published guidelines for the prevention and treatment of CMV infection and disease. CONCLUSIONS: The prognosis of CMV disease in the BMT recipients has improved as a result of a wide variety of modifications in the management of BMT recipients. These include an increased understanding of the risk factors associated with CMV infection, routine screening for CMV replication and excretion, and more effective prophylactic regimens. Still, more than half of the patients who develop pneumonia will die, indicating that more studies are needed to increase the understanding of the pathophysiology and refine the preventive and therapeutic regimens against CMV.