Vaccine and Infectious Disease Division

Determining risk factors for CMV acquisition

Approximately 1 million people in the United States are currently living with or in remission from hematologic malignancies, including leukemia, lymphoma and myeloma.  Hematopoietic stem cell transplantation (HCT) is a procedure for restoring a cancer patient’s marrow cells to normal levels and is one of the most commonly used treatments for leukemia and lymphoma. Chemotherapy and/or radiation are used to disrupt the patient’s immune system prior to HCT to provide the most hospitable environment for successful transplant, but as a consequence the patient’s immune system is compromised and not fully competent to fight off infections for up to a year. Cytomegalovirus (CMV) is a β-herpesvirus that causes lifelong infection of the host and usually stays under the radar, living quietly in a latent state, but can morph from benign to pathogenic in those with compromised immune systems. CMV is the most frequent viral complication in post-HCT recipients. Great strides in prevention of HCT-related CMV complications have been made in the last several decades with administration of antiviral prophylaxis and donor graft screening. However, little is known about risk factors for CMV transmission in those patients who are CMV seronegative and receive a seropositive graft from a seropositive donor.

To investigate potential risk-factors for CMV transmission in CMV positive donor/CMV negative recipient transplantations, VIDD assistant member Dr. Steven Pergam, in collaboration with VIDD member Dr. Michael Boeckh and Center president /director Dr. Larry Corey and multiple other center faculty and staff, performed a retrospective clinical trial of the Center’s HCT recipients. Between January 1995 and December 2007, 447 patients in which recipients were CMV- and donors were CMV+ underwent HCT at the Hutchison Center. Most patients underwent HCT for acute and chronic leukemias, and all subjects were monitored for CMV seroconversion for up to one year using one of two detection methods for CMV infection: antigen detection (antigenemia) and PCR. The authors found that 19 percent of study subjects had detectable CMV within a year post-transplantation and of these 17 percent before 100 days; the median time to seroconversion was 49 days. Only 1.3 percent of patients developed CMV disease within 100 days post-transplant. In an analysis of risk factors for CMV transmission, the authors found a significantly higher risk when patients received donor grafts with a higher number of total nucleated cells in the donor graft (HR, 2.7; 95 percent CI, 1.6-4.7). These data are the most comprehensive description of CMV complications in this population, help to define the importance of the donor graft as the most frequent source of CMV transmission in CMV positive donor/CMV negative recipients, and may lead to future interventions to predict and prevent CMV transmission for these at-risk patients.

Pergam SA, Xie H, Sandhu R, Pollack M, Smith J, Stevens-Ayers T, Ilieva V, Kimball LE, Huang ML, Hayes TS, Corey L, Boeckh MJ. Efficiency and Risk Factors for CMV Transmission in Seronegative Hematopoietic Stem Cell Recipients. Biol Blood Marrow Transplant. 2012 Mar 3.