Management of CMV Infections after Bone Marrow Transplantation: A Paradigm Shift

Abstract

Cytomegalovirus (CMV) historically has been the major infectious cause of death after allogeneic bone marrow transplantation (BMT). During the 1970s and 1980s, clinical trials identified risk factors for CMV disease. During the 1980s, new diagnostic tools led to more accurate and earlier detection of disease and identified patients with active infection before the onset of disease. These methods permitted the development of strategies to prevent infected patients from developing disease, which in the 1990s culminated in substantial reduction in CMV morbidity and mortality. In seronegative patients, prevention of acquisition of virus from blood product support has proven to be highly effective. In other patients (who are already infected or whose donor is infected), the use of immunoglobulin and, more recently, several antiviral prophylactic or “pre-emptive therapies” have proven to be highly effective. Unfortunately, once antiviral therapy is stopped, infection can recur with subsequent disease. The increasing use of alternate donors, where the recipient may have slower recovery of protective immune responses, and the growing choice of peripheral blood over marrow as stem cell source, with attendant greater risk for chronic graft-versus-host disease (GvHD) are changes in transplant practices that have led to more individuals with delayed recovery of protective immune responses. Thus, we have seen a shift from early onset CMV disease (that is now controlled) to late onset disease. New strategies are needed to identify at-risk patients and to prevent late onset disease.