Late Cytomegalovirus Infections After Allogeneic Hematopoietic Cell Transplant

Graft versus host disease (GVHD) prophylaxis with posttransplant cyclophosphamide (ptCY) and cytomegalovirus (CMV) prophylaxis with letermovir have changed the clinical epidemiology of CMV infection. We studied the incidence, risk factors for, and outcomes of CMV infection after Day + 90 of allogeneic hematopoietic cell transplant (alloHCT). The patient cohort consisted of 2106 alloHCT patients treated from 2015 to 2022 with a single alloHCT. Fifty-seven percent of patients received ptCY. Forty-three percent of patients received letermovir. We performed landmark analysis of the cumulative incidence of CMV-emia with the competing risk of death from Day + 0 to +360 in 90-day intervals. Regression analyses of baseline and time-dependent covariates for CMV-emia and survival were performed for each interval. The cumulative incidence of CMV-emia (≥ 500 IU CMV DNA/mL) was associated with donor/recipient CMV serostatus. In the highest risk CMV serostatus donor negative and recipient positive (D-R+) group, the cumulative incidence was 24.3 (95% confidence interval [CI] 21.3-27.3), 9 (95% CI: 6.9-11.1), 5 (95% CI: 3.3-6.7), and 2.1 (95% CI: 0.9-3.3) from Day 0 to 90, 91 to 180, 181 to 270, and 271 to 360, respectively. The primary risk factors associated with CMV incidence were related to acute GVHD. PtCY was associated with a decreased risk of CMV infection. Letermovir prophylaxis did not associate with decreased CMV infection after Day + 90. In conclusion, the risk of CMV infection remains clinically significant until Day + 180, although this is affected by the GVHD status of the patient. Discontinuation of letermovir may be considered after Day + 180.