Background: The impact of pretransplant cytomegalovirus (CMV) serology and DNAemia on posttransplant clinically significant CMV infections (csCMVi) in allogeneic hematopoietic cell transplant recipients (allo-HCTR) is poorly described.

Methods: We performed a single-center cohort study of adult allo-HCTR (16 November 2015-31 December 2023). Letermovir prophylaxis was administered after 01 May 2019 during 100 days (d) posttransplant in CMV-seropositive patients (R+). We investigated associations of pretransplant CMV-IgG-titers and CMV-DNAemia with posttransplant csCMVi and CMV-DNAemia during 6 months posttransplant. In CMVR+, CMV-IgG-titers were classified as "low" (<40 IU/mL) or "high" (≥40 IU/mL). Quantitative CMV-PCR was performed pre-HCT, weekly for 3 months and as clinically indicated.

Results: Among the 485 patients included, 209 and 276 underwent a first allo-HCT in the pre- and postletermovir periods, respectively; 314/485 (64.7%) patients were CMVR + . Patients with high CMV-IgG-titers had a higher incidence of csCMVi by d180 posttransplant (47.6%, 95% CI: 41.4-53.6) than those with low CMV-IgG-titers (22.5%, 95% CI: 11.5-35.7) and CMVR- (3.6%, 95% CI: 1.5-7.2, P < .001), and higher incidence of any CMV-DNAemia (P < .001). Overall, 61/485 (12.6%) patients had detectable/quantifiable pretransplant CMV-DNAemia, with higher posttransplant incidence of csCMVi by d180 (61.3%, 95% CI: 47.6-72.4) compared to those with undetectable pretransplant CMV-DNAemia (26.9%, 95% CI: 22.3-31.6, P < .001) and higher incidence of any CMV-DNAemia (P < .001). Pretransplant high CMV-IgG-titers (aHR: 14.18, P < .001) and CMV-DNAemia (aHR: 2.43, P < .001) were strong predictors of posttransplant csCMVi.

Conclusions: Pretransplant high CMV-IgG-titers and detectable/quantifiable DNAemia were associated with higher posttransplant csCMVi/CMV-DNAemia incidence, including in the letermovir era. Additional studies on the clinical utility of baseline pretransplant CMV burden in CMV prophylaxis stratification algorithms are needed.