Cytomegalovirus Infection Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation from a Single Institution

Abstract

Human cytomegalovirus (CMV) infection and disease remains a significant cause of morbidity and mortality for hematopoietic cell transplantation (HCT) recipients. Disruption of or weak reconstitution of virus-specific cellular immune function, such as with certain HCT approaches, poses significant risk for CMV-related complications. The incidence of and risk factors for CMV infection and the nature of CMV disease were evaluated retrospectively among 356 consecutive HCT recipients transplanted at the National Institutes of Health using all graft sources, including bone marrow, peripheral blood stem cell (PBSC), and umbilical cord blood (UCB), and a range of in vivo and ex vivo approaches for graft-versus-host disease (GVHD) prophylaxis. The cumulative incidence of CMV infection was higher for CMV-seropositive recipients at 33%, regardless of donor CMV serostatus. Patients transplanted with CMV-seropositive donors had a significantly shorter duration of antiviral therapy. Among graft sources UCB was associated with the highest cumulative incidence of CMV infection at 65% and significantly longer treatment duration at a median of 36 days, whereas PBSC HCT was associated with the lowest incidence at 26% and the shortest CMV treatment duration at a median of 21 days. There were significant differences in the cumulative incidence of CMV infection by T cell manipulation strategy when systemic steroids were included as a risk-modifying event. Over one-third of CMV infections occurred in the setting of systemic steroid administration. CMV disease occurred in 5% of HCT recipients, with 70% of cases in the setting of treatment for GVHD. Although factors related to serostatus, graft source, and GVHD prophylaxis were associated with varied CMV infection incidence, unplanned post-HCT corticosteroid therapy contributed greatly to the incidence of both CMV infection and disease across HCT approaches, highlighting this post-HCT intervention as a key time to potentially tailor the approach to monitoring, preemptive therapy, and even prophylaxis.

Prospective Study of a Novel, Radiation-Free, Reduced-Intensity Bone Marrow Transplantation Platform for Primary Immunodeficiency Diseases

“…No patients had clinically significant EBV-associated complications, consistent with outcomes previously published with PTCy-based approaches [51]. CMV reactivation was controlled with pre-emptive therapy alone in all but 1 patient, which could in part be associated with the use of sirolimus [16,52]. Notably, post-BMT primary CMV infection was not uncommon; all cases occurred after weekly CMV monitoring had stopped, and 1 case progressed to CMV disease.…”

“…Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6, adenovirus, and BK virus were evaluated weekly in blood and, for BK virus, also urine by quantitative PCR. CMV monitoring and preemptive treatment were performed as previously published [16].…”

Cytomegalovirus Infection in Allogeneic Hematopoietic Cell Transplantation Managed by the Preemptive Approach: Estimating the Impact on Healthcare Resource Utilization and Outcomes

“…Cytomegalovirus (CMV) viremia occurs in 40% to D 1 2 7 X X90% of CMV-D 1 2 8 X Xseropositive recipients (R + ) [1À3] and is associated with increased overall mortality after hematopoietic cell transplantation (HCT) [4]. Risk factors for CMV reactivation after HCT are well established and include T D 1 2 9 X Xcell depletion, allograft from D 1 3 0 X XHLA-mismatched or CMV-seronegative donor (D ¡ ), and graft-D 1 3 1 X Xversus-D 1 3 2 X Xhost disease (GVHD) [1,4]. Preemptive therapy (PET) has reduced the rates of CMV end-organ disease to less than 5% [5], the trade-off being increased use of CMV antivirals with their associated toxicities and potentially prolonged hospital length of stay (LOS).…”

Incidence of viral and fungal complications after utilization of alternative donor sources in hematopoietic cell transplantation

“…A summary of selected studies reporting CMV incidence can be found in Table 2. When compared to other graft sources, UCB transplants have been reported to have higher cumulative incidences of CMV infection and CMV disease 6, 26, 29 . The risk of CMV is also much higher in CMV seropositive recipients.…”