Late Cytomegalovirus Infections After Allogeneic Hematopoietic Cell Transplant

Area of Science:

• Hematology
• Infectious Diseases
• Transplant Immunology

Background:

• Cytomegalovirus (CMV) infection is a major complication following allogeneic hematopoietic cell transplant (alloHCT).
• Prophylaxis strategies, including posttransplant cyclophosphamide (ptCY) for graft-versus-host disease (GVHD) and letermovir for CMV, have evolved.
• The impact of these strategies on CMV infection epidemiology after day 90 requires further investigation.

Purpose of the Study:

• To determine the incidence, risk factors, and outcomes of CMV infection after day 90 in alloHCT recipients.
• To evaluate the effect of ptCY and letermovir prophylaxis on CMV infection rates post-day 90.
• To identify key factors influencing CMV infection risk in the late post-transplant period.

Main Methods:

• Landmark analysis of CMV-emia (≥500 IU CMV DNA/mL) in 2106 alloHCT patients from 2015-2022.
• Competing risk analysis of death from day 0 to day 360 in 90-day intervals.
• Regression analyses of baseline and time-dependent covariates for CMV-emia and survival.

Main Results:

• The cumulative incidence of CMV-emia varied significantly by donor/recipient CMV serostatus, highest in the D-R+ group (24.3% by day 90, decreasing over time).
• Acute GVHD was a primary risk factor for CMV incidence.
• ptCY prophylaxis was associated with a decreased risk of CMV infection, whereas letermovir did not show a significant association with decreased CMV infection after day 90.

Conclusions:

• CMV infection risk remains clinically significant up to day 180 post-alloHCT, influenced by GVHD status.
• ptCY prophylaxis demonstrates a protective effect against CMV infection.
• Letermovir prophylaxis may not be necessary beyond day 180, suggesting potential for discontinuation.