Cytomegalovirus DNA Doubling Time for Early Identification of Clinically Significant Infection Episodes in Allogeneic Hematopoietic Stem Cell Transplant Recipients Undergoing Primary Letermovir Prophylaxis: A Multicenter Study.

Letermovir (LMV) prophylaxis currently represents the first-line strategy for preventing clinically significant cytomegalovirus (CMV) infection (CsCMVi) in CMV-seropositive recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). A wide variety of CMV DNA thresholds for LMV interruption and preemptive antiviral therapy (PET) inception are in place across transplantation centers. We evaluated the potential of CMV DNA doubling time (dt) in plasma to distinguish between CsCMVi and abortive CMV infection in allo-HSCT recipients on primary LMV prophylaxis. Data from the Spanish Hematopoietic Transplantation and Cell Therapy Group multicenter registry included 296 allo-HSCT patients receiving LMV prophylaxis. Participating centers used a plasma CMV DNA threshold of ≥1000 IU/mL for initiating PET. The CMV DNA dt was calculated from the first two or three positive polymerase chain reaction (PCR) results based on pre-established criteria. CMV DNAemia developed in 64 recipients (21.6%) with a total of 88 episodes, of which CsCMVi occurred in 9 recipients (3.04%) and included 10 episodes (one patient had confirmed CMV gastrointestinal disease). A non-calculable CMV DNA dt had a negative predictive value of 94% for CsCMVi. For initial episodes with calculable CMV DNA dts (4/7 CsCMVi and 8/57 no-CsCMVi), a threshold of >2.35 days had a specificity of 100% for ruling out CsCMVi. CMV DNA dt could optimize CMV infection management in allo-HSCT patients under LMV prophylaxis, independent of the PCR platform used.