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

We evaluated the potential of Cytomegalovirus (CMV) DNA doubling time (dt) in plasma to distinguish between clinically significant CMV infection (CsCMVi) and abortive CMV infection in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on primary letermovir (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 ≥ 1,000 IU/ml for initiating preemptive antiviral therapy (PET). The CMV DNA dt was calculated from the first two or three positive 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 (NPV) 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 positive predictive value of 100% for CsCMVi. CMV DNA dt could optimize CMV infection management in allo-HSCT patients under LMV prophylaxis, independent of the PCR platform used.