Division of Pediatric Allergy, Immunology and Bone Marrow Transplant, University of California San Francisco, San Francisco, California, USA.
Division of Pediatrics Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
J Pediatric Infect Dis Soc. 2021 Apr 30;10(4):417-425. doi: 10.1093/jpids/piaa119.
Children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) are at high risk for invasive fungal disease (IFD).
This multicenter, randomized, open-label trial planned to enroll 560 children and adolescents (3 months to <21 years) undergoing allogeneic HCT between April 2013 and September 2016. Eligible patients were randomly assigned to antifungal prophylaxis with caspofungin or a center-specific comparator triazole (fluconazole or voriconazole). Prophylaxis was administered from day 0 of HCT to day 42 or discharge. The primary outcome was proven or probable IFD at day 42 as adjudicated by blinded central review. Exploratory analysis stratified this evaluation by comparator triazole.
A planned futility analysis demonstrated a low rate of IFD in the comparator triazole arm, so the trial was closed early. A total of 290 eligible patients, with a median age of 9.5 years (range 0.3-20.7), were randomized to caspofungin (n = 144) or a triazole (n = 146; fluconazole, n = 100; voriconazole, n = 46). The day 42 cumulative incidence of proven or probable IFD was 1.4% (95% confidence interval [CI], 0.3%-5.4%) in the caspofungin group vs 1.4% (95% CI, 0.4%-5.5%) in the triazole group (P = .99, log-rank test). When stratified by specific triazole, there was no significant difference in proven or probable IFD at day 42 between caspofungin vs fluconazole (1.0%, 95% CI, 0.1%-6.9%, P = .78) or caspofungin vs voriconazole (2.3%, 95% CI, 0.3%-15.1%, P = .69).
In pediatric HCT patients, prophylaxis with caspofungin did not significantly reduce the cumulative incidence of early proven or probable IFD compared with triazoles. Future efforts to decrease IFD-related morbidity and mortality should focus on later periods of risk.
NCT01503515.
接受异基因造血细胞移植（HCT）的儿童和青少年存在侵袭性真菌病（IFD）的高风险。
这项多中心、随机、开放标签试验计划招募 2013 年 4 月至 2016 年 9 月期间接受异基因 HCT 的 560 名儿童和青少年（3 个月至<21 岁）。符合条件的患者被随机分配接受卡泊芬净或中心特异性比较三唑类药物（氟康唑或伏立康唑）进行预防治疗。预防治疗从 HCT 第 0 天开始，持续至第 42 天或出院。主要结局是由盲法中心审查判定的第 42 天确诊或疑似 IFD。探索性分析按比较三唑类药物分层了该评估。
一项计划的无效性分析显示比较三唑类药物组的 IFD 发生率较低，因此试验提前关闭。共有 290 名符合条件的患者，中位年龄为 9.5 岁（范围 0.3-20.7），随机分为卡泊芬净组（n=144）或三唑类药物组（n=146；氟康唑，n=100；伏立康唑，n=46）。卡泊芬净组第 42 天确诊或疑似 IFD 的累积发生率为 1.4%（95%置信区间 [CI]，0.3%-5.4%），三唑类药物组为 1.4%（95%CI，0.4%-5.5%）（P=0.99，对数秩检验）。当按特定三唑类药物分层时，卡泊芬净与氟康唑（1.0%，95%CI，0.1%-6.9%，P=0.78）或卡泊芬净与伏立康唑（2.3%，95%CI，0.3%-15.1%，P=0.69）在第 42 天确诊或疑似 IFD 方面无显著差异。
在儿科 HCT 患者中，与三唑类药物相比，卡泊芬净预防治疗并未显著降低早期确诊或疑似 IFD 的累积发生率。降低 IFD 相关发病率和死亡率的未来努力应侧重于风险较高的后期。
NCT01503515。
