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Basic Characteristics of Mutations
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Mutation Site
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C325Y |
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Mutation Site Sentence
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A single C325Y resistance mutation was identified in an umbilical cord blood recipient. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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UL56 |
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Standardized Encoding Gene
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UL56
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cytomegalovirus infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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letermovir |
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Location
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- |
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Literature Information
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PMID
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36693927
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Title
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Cytomegalovirus breakthrough and resistance during letermovir prophylaxis
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Author
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Perchetti GA,Biernacki MA,Xie H,Castor J,Joncas-Schronce L,Ueda Oshima M,Kim Y,Jerome KR,Sandmaier BM,Martin PJ,Boeckh M,Greninger AL,Zamora D
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Journal
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Bone marrow transplantation
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Journal Info
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2023 Apr;58(4):430-436
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Abstract
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Letermovir is a relatively new antiviral for prophylaxis against cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT). CMV-seropositive HCT recipients who received letermovir prophylaxis from 2018 to 2020 at our center were evaluated for letermovir resistance and breakthrough CMV reactivation. Two-hundred twenty-six letermovir recipients were identified and 7/15 (47%) with CMV DNAemia >/=200 IU/mL were successfully genotyped for UL56 resistance. A single C325Y resistance mutation was identified in an umbilical cord blood recipient. Ninety-five (42%), 43 (19%), and 15 (7%) patients had breakthrough CMV at any level, >/=150 IU/mL, and >/=500 IU/mL, respectively. Risk factors for breakthrough CMV reactivation at each viral threshold were examined. Cumulative steroid exposure was the strongest risk factor for CMV at all evaluated viral thresholds. Graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide (aHR 2.34, 95% CI 1.28-4.28, p = 0.001) or calcineurin inhibitors plus mycophenolate (aHR 2.24, 95% CI 1.30-3.86, p = 0.004) were also associated with an increased risk of CMV reactivation at any level. De novo letermovir resistance is rare and can be successfully treated using other antivirals. Letermovir effectively prevents clinically significant CMV, however, subclinical CMV reactivation occurs frequently at our center.
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Sequence Data
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-
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