Impact of Multiple Episodes of Cytomegalovirus Infection on Patient Outcomes in Allogeneic Hematopoietic Stem Cell Transplant Using a Pre-emptive Monitoring Strategy

The impact of multiple episodes of clinically significant cytomegalovirus infection (csCMVi) on clinical outcomes during pre-emptive CMV monitoring in allogeneic hematopoietic stem cell transplant recipients (HCT) is not well understood. We performed a retrospective cohort study of all consecutive patients undergoing their first allogeneic HCT at Duke between January 1, 2009 and December 31, 2013, during an era of pre-emptive CMV monitoring, prior to widespread use of letermovir prophylaxis. Consensus definitions were utilized for refractory and resistant CMV infection, bacteremia, invasive fungal disease, and renal dysfunction. The Kaplan-Meier method was used to estimate survival. Three hundred eighty-eight adult patients underwent allogeneic HCT during the study time period with 91 patients (23%) having one episode of csCMVi and 79 patients (20%) having [≥] one episode of csCMVi. Risk factors for multiple episodes of csCMVi included having a transplant from a matched unrelated donor, cord blood as HCT source, and graft-versus-host disease prophylaxis with highly T-cell suppressive agents such as alemtuzumab. Patients with multiple episodes tended to develop csCMVi earlier post-transplant and were more likely to have CMV disease and to develop resistant CMV infection. There was no difference in rates of refractory CMV infection, bacteremia, invasive fungal disease, or survival. However, patients with multiple episodes of csCMV had reduced one-year relapse-related mortality compared to patients with one csCMVi episode.