ArticleTransplant infectious disease : an official journal of the Transplantation Society
Associations of Nucleoside Diphosphate-Linked Moiety X-Type Motif 15 Variants With Neutropenia During Antiviral Therapy for Cytomegalovirus Disease in Pediatric Liver Transplant Recipients.
Article in Transplant infectious disease : an official journal of the Transplantation Society. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Associations of Nucleoside Diphosphate-Linked Moiety X-Type Motif 15 Variants With Neutropenia During Antiviral Therapy for Cytomegalovirus Disease in Pediatric Liver Transplant Recipients.Transplant infectious disease : an official journal of the Transplantation SocietyArticle
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8 authors.
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Abstract
backgroundCytomegalovirus (CMV) infection in pediatric liver transplant recipients is a major concern. Ganciclovir (GCV) and valganciclovir (VGCV) are the first-line treatment agents; however, neutropenia is a common adverse effect. Nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) variants are linked to thiopurine-induced myelosuppression; however, their associations with GCV/VGCV-induced cytotoxicity remain unclear. We aimed to examine the association between loss-of-function variants of the NUDT15 genotype and drug-related adverse reactions in pediatric transplant recipients, specifically liver transplant recipients, treated with GCV/VGCV.
methodsWe retrospectively analyzed data from pediatric liver transplant recipients treated with GCV/VGCV for CMV disease or infection between 2012 and 2022. Patients were genotyped for NUDT15 R139C, R139H, and V18I variants, and hematological outcomes were compared between the normal and variant groups.
resultsOf 40 patients, 10 (25%) harbored NUDT15 variants. The incidence rate of neutropenia (60% vs. 7%; p < 0.01) and percentage decrease in neutrophil count (-65.1% vs. -45.9%; p = 0.02) were significantly higher in the variant group than in the normal group. No significant differences were observed in the incidence of leukopenia, anemia, thrombocytopenia, hepatic toxicity, or renal toxicity.
conclusionNUDT15 variants were associated with an increased risk of neutropenia in pediatric liver transplant recipients receiving GCV/VGCV treatment. Genetic screening before treatment initiation may help optimize antiviral therapy, minimize hematological toxicity, and improve patient management. Further studies are needed to refine the treatment strategies.
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