Salih Demirhan , Flor M. Munoz , Kristen G. Valencia Deray , Claire E. Bocchini , Lara Danziger-Isakov , Samantha Blum , Tanvi S. Sharma , Gilad Sherman , Juri Boguniewicz , Samantha Bacon , Monica I. Ardura , Gabriela M. Maron , Jose Ferrolino , Marc Foca , Betsy C. Herold
{"title":"在儿童实体器官移植受者中,体表面积与体重相比,缬更昔洛韦的剂量与毒性增加有关。","authors":"Salih Demirhan , Flor M. Munoz , Kristen G. Valencia Deray , Claire E. Bocchini , Lara Danziger-Isakov , Samantha Blum , Tanvi S. Sharma , Gilad Sherman , Juri Boguniewicz , Samantha Bacon , Monica I. Ardura , Gabriela M. Maron , Jose Ferrolino , Marc Foca , Betsy C. Herold","doi":"10.1016/j.ajt.2023.07.013","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>Optimal dosing of valganciclovir (VGCV) for </span>cytomegalovirus<span><span> (CMV) prevention in pediatric </span>solid organ transplantation<span> recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (</span></span></span><em>P</em> = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (<em>P</em> = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, <em>P</em><span> <.001), lymphopenia (51% vs 15.0%, </span><em>P</em><span> <.001), and acute kidney injury<span> causing treatment modification (8.0% vs 1.8%, </span></span><em>P</em><span> <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.</span></p></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"23 12","pages":"Pages 1961-1971"},"PeriodicalIF":8.9000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Body surface area compared to body weight dosing of valganciclovir is associated with increased toxicity in pediatric solid organ transplantation recipients\",\"authors\":\"Salih Demirhan , Flor M. Munoz , Kristen G. Valencia Deray , Claire E. Bocchini , Lara Danziger-Isakov , Samantha Blum , Tanvi S. Sharma , Gilad Sherman , Juri Boguniewicz , Samantha Bacon , Monica I. Ardura , Gabriela M. Maron , Jose Ferrolino , Marc Foca , Betsy C. Herold\",\"doi\":\"10.1016/j.ajt.2023.07.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span>Optimal dosing of valganciclovir (VGCV) for </span>cytomegalovirus<span><span> (CMV) prevention in pediatric </span>solid organ transplantation<span> recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (</span></span></span><em>P</em> = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (<em>P</em> = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, <em>P</em><span> <.001), lymphopenia (51% vs 15.0%, </span><em>P</em><span> <.001), and acute kidney injury<span> causing treatment modification (8.0% vs 1.8%, </span></span><em>P</em><span> <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.</span></p></div>\",\"PeriodicalId\":123,\"journal\":{\"name\":\"American Journal of Transplantation\",\"volume\":\"23 12\",\"pages\":\"Pages 1961-1971\"},\"PeriodicalIF\":8.9000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Transplantation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1600613523005841\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Transplantation","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1600613523005841","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0
摘要
缬更昔洛韦(VGCV)预防儿童实体器官移植(SOTR)巨细胞病毒(CMV)的最佳剂量存在争议。建议根据体表面积(BSA)和肌酐清除率计算剂量,但通常规定简化体重(BW)剂量。我们进行了一项6个中心的回顾性研究,比较这些策略在移植后第一年的安全性和有效性。有100例(24.2%)儿童SOTR接受BSA治疗,312例(75.7%)接受BW治疗。在接受BSA和BW治疗的儿童SOTR中,第一年任何时候CMV dna血症的发生率分别为31.0%和23.4% (P = 0.1),突破dna血症的发生率分别为16%和12.2% (P = 0.3)。然而,中性粒细胞减少症(50% vs 29.3%, P
Body surface area compared to body weight dosing of valganciclovir is associated with increased toxicity in pediatric solid organ transplantation recipients
Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (P = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (P = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, P <.001), lymphopenia (51% vs 15.0%, P <.001), and acute kidney injury causing treatment modification (8.0% vs 1.8%, P <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.
期刊介绍:
The American Journal of Transplantation is a leading journal in the field of transplantation. It serves as a forum for debate and reassessment, an agent of change, and a major platform for promoting understanding, improving results, and advancing science. Published monthly, it provides an essential resource for researchers and clinicians worldwide.
The journal publishes original articles, case reports, invited reviews, letters to the editor, critical reviews, news features, consensus documents, and guidelines over 12 issues a year. It covers all major subject areas in transplantation, including thoracic (heart, lung), abdominal (kidney, liver, pancreas, islets), tissue and stem cell transplantation, organ and tissue donation and preservation, tissue injury, repair, inflammation, and aging, histocompatibility, drugs and pharmacology, graft survival, and prevention of graft dysfunction and failure. It also explores ethical and social issues in the field.