Liverman Rochelle, Serluco Anastacia, Nance Gwen, George Roshan, Rodriguez Dellys Soler, Deshpande Shriprasad, Mao Chad, Garro Rouba, Yildirim Inci
Children's Healthcare of Atlanta, Georgia, Atlanta, USA.
Joe DiMaggio Children's Hospital, Florida, Hollywood, USA.
Pediatr Transplant. 2023 Jun;27(4):e14493. doi: 10.1111/petr.14493. Epub 2023 Mar 21.
Cytomegalovirus (CMV) is associated with morbidity and mortality in solid organ transplant recipients (SOTR). Valganciclovir (VGC) is extensively used for prophylaxis. Optimal dosing in children, risk factors for failure, and the impact of dose adjustments on CMV DNAemia is not well established.
This retrospective cohort study of pediatric SOTR transplanted between 2010-2018 evaluated the epidemiology of CMV DNAemia and used Cox-regression to assess the risk factors for CMV DNAemia within one-year following SOTR.
In 393 pediatric SOTR (heart [96, 24.4%], kidney [180, 45.6%], liver [117, 29.8%]; median age 9.5 ± 0.3 years), overall CMV DNAemia incidence was 6.6/10 000 days (95%CI 5.1/10 000-7.9/10 000) and varied by organ groups: heart 8.2/10 000 days (95%CI 4.9/10 000-11.4/10 000), kidney 5.8/10 000 days (95%CI 3.9/10 000-7.8/10 000), liver 6.2/10 000 days (95%CI 3.7/10 000-8.7/10 000). CMV DNAemia was detected in 75 of 275 (27.2%) patients who received prophylaxis (40 cases occurred during prophylaxis and 35 occurred after completion of prophylaxis). The median VGC dose given according to institutional weight-based algorithm was approximately 1.5-fold lower than the manufacturer-recommended dose. This discordance was more prominent at younger age groups (3.2-fold lower in <2-year-old [100 mg versus 325 mg], 2.5-fold lower in <6-year-old [200 mg versus 447 mg]). Dose reduction due to adverse events was an independent risk factor for breakthrough CMV DNAemia (hazard ratio 2.2, 95%CI 1.2-3.8) among patients with similar age, CMV risk stratification, starting VGC dose, immunosuppressive therapy, and organ group.
CMV events occurred while on VGC prophylaxis. Weight-based VGC may prevent supratherapeutic VGC exposure especially in younger children. Dose reduction of VGC prophylaxis for adverse event management places patients at an increased risk for CMV DNAemia suggesting other agents with fewer adverse effects should be considered and need to be studied in children.
巨细胞病毒（CMV）与实体器官移植受者（SOTR）的发病率和死亡率相关。缬更昔洛韦（VGC）被广泛用于预防。儿童的最佳剂量、治疗失败的危险因素以及剂量调整对CMV血症的影响尚未完全明确。
这项对2010年至2018年间接受移植的儿科SOTR进行的回顾性队列研究评估了CMV血症的流行病学情况，并使用Cox回归分析评估SOTR后一年内CMV血症的危险因素。
在393例儿科SOTR（心脏移植96例，占24.4%；肾脏移植180例，占45.6%；肝脏移植117例，占29.8%；中位年龄9.5±0.3岁）中，总体CMV血症发病率为6.6/10000天（95%CI 5.1/10000 - 7.9/10000），且因器官组而异：心脏移植为8.2/10000天（95%CI 4.9/10000 - 11.4/10000），肾脏移植为5.8/10000天（95%CI 3.9/10000 - 7.8/10000），肝脏移植为6.2/10000天（95%CI 3.7/10000 - 8.7/10000）。在接受预防治疗的275例患者中有75例（27.2%）检测到CMV血症（40例发生在预防治疗期间，35例发生在预防治疗结束后）。根据机构基于体重的算法给出的VGC中位剂量比制造商推荐剂量低约1.5倍。这种差异在较年轻年龄组更为明显（<2岁儿童低3.2倍[100mg对325mg]，<6岁儿童低2.5倍[200mg对447mg]）。在年龄、CMV风险分层、开始使用VGC剂量、免疫抑制治疗和器官组相似的患者中，因不良事件而降低剂量是突破性CMV血症的独立危险因素（风险比2.2，95%CI 1.2 - 3.8）。
在接受VGC预防治疗期间发生了CMV事件。基于体重的VGC可能预防VGC超治疗剂量暴露，尤其是在年幼儿童中。为管理不良事件而降低VGC预防剂量会使患者发生CMV血症的风险增加，这表明应考虑其他不良反应较少的药物，并需要在儿童中进行研究。
