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After 6 years of use, a large body of real\u2010world experience has been accumulated that validates the Phase III clinical trial results, in which LMV was shown to significantly reduce the risk of clinically significant CMV infection\u2014defined as CMV end\u2010organ disease or CMV DNAemia requiring pre\u2010emptive antiviral therapy (PET)\u2014and increase survival up to Week 24 after treatment inception. Notwithstanding, several issues still need to be settled, thus further investigation is required. First, since viral DNA may accumulate as a result of LMV\u2010driven abortive CMV infection, what is the optimal viral load threshold in the blood that would prompt LMV prophylaxis interruption and PET inception? Should this be adapted to the patient's risk? Second, what is the impact of LMV prophylaxis on the reconstitution of functional CMV\u2010specific T\u2010cell responses? Would it be a wise approach to individually tailor the duration of LMV treatment according to the number of peripheral blood CMV\u2010specific T cells at the end of regular prophylaxis? Third, how frequently do LMV\u2010resistant strains arise while patients are on LMV prophylaxis and how could this be minimized? Here, we discuss the literature addressing these topics.<\/jats:p>","DOI":"10.1002\/jmv.29005","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T12:44:37Z","timestamp":1690893877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review"],"prefix":"10.1002","volume":"95","author":[{"given":"Carlos","family":"Solano","sequence":"first","affiliation":[{"name":"Hematology Service Hospital Cl\u00ednico Universitario, INCLIVA Health Research Institute Valencia Spain"},{"name":"Department of Medicine School of Medicine, University of Valencia Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela","family":"Gim\u00e9nez","sequence":"additional","affiliation":[{"name":"INCLIVA Health Research Institute 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