Pre-engraftment Cytomegalovirus DNAemia
Condition: CMV DNAemia Pre-engraftment
Study type: Observational

Summary: 
      Cytomegalovirus (CMV) DNAemia occurs frequently in allogeneic hematopoietic stem cell
      transplant (allo-HSCT) recipients.Both high-level and persistent virus DNAemia are known risk
      factors for CMV end-organ disease and perhaps non-relapse mortality. CMV DNAemia is usually
      documented after engraftment, but it may occur before. The virological features and clinical
      consequences of these latter early-onset episodes remain largely unexplored. The U.S. Food
      and Drug Administration (FDA) has recently approved letermovir for prophylaxis of CMV
      infection and disease in adult CMV-seropositive allo-HSCT recipients (PREVYMIS™, Merck & Co.,
      New Jersey, USA). In accordance with the design of the phase III, double-blind trial the drug
      may be administered as early as the day of transplant and no later than 28 days
      post-transplant. Nevertheless, the timing of drug inception should be contingent on the
      clinical impact of very early episodes of CMV DNAemia. In a recent work from our group
      (single-center study) we found that a total 38 out of the 197 patients in our series
      developed CMV DNAemia before engraftment (cumulative incidence (CI), 19%; 95% CI, 10-30.3%).
      Nine episodes of CMV DNAemia were detected prior to the time of donor progenitor cell
      infusion. A greater number of post-engraftment episodes required preemptive antiviral therapy
      compared with pre-engraftment episodes (62.5% vs 44.7%; P=0.05). The cellular content of the
      donor progenitor cell infusion and transplant characteristics of patients did not differ
      between patients with pre- or post-engraftment CMV DNAemia. The cumulative incidence of
      overall mortality by days 100 and 365, aGvHD by day 100 and relapse by day 365 were not
      significantly different between patients with pre-engraftment or post-engraftment CMV
      DNAemia. Our study was limited by the retrospective and single-center design and the scarce
      number of pre-engraftment CMV DNAemia episodes included; therefore, the results may not be
      extrapolated to other transplantation centers or patient cohorts. Further retrospective and
      prospective studies are thus required to validate the data presented herein.
    

Detailed description: 
      Episodes of CMV DNAemia developing prior to engraftment (pre-CMV DNAemia), which usually
      occur between the third and fourth week after allo-HSCT, may conceivably have a different
      course from episodes emerging after engraftment once patients have begun to expand
      donor-derived T cells (post-CMV DNAemia). Thus, whether the precise timing of Letermovir
      treatment initiation should matter will ultimately depend on the impact of CMV DNAemia
      episodes developing prior to engraftment on clinical outcomes. There is limited information
      available on this topic. Here, we conducted a retrospective multicenter, non-interventional
      study to further address this issue.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        All consecutive allo-HSCT recipients at risk of CMV infection allografted from 1st January
        2010 until 31th December 2017 in Spanish transplant centers