Gottschlich Anna Sophia, Ernst Jana, Milde Till, Gruhn Bernd
Department of Pediatrics, Jena University Hospital, Jena, Germany.
Comprehensive Cancer Center Central Germany (CCCG), Jena, Germany.
J Cancer Res Clin Oncol. 2025 Aug 23;151(8):235. doi: 10.1007/s00432-025-06289-5.
Invasive fungal diseases (IFDs) are a significant cause of morbidity and mortality in pediatric patients with hematologic malignancies including acute leukemia. Our study aimed to compare the efficacy of liposomal amphotericin B (L-AMB), posaconazole or micafungin as primary antifungal prophylaxis (PAP) in pediatric patients with acute leukemia.
This retrospective observational study enrolled 95 pediatric patients with acute lymphoblastic leukemia (n = 70) or acute myeloid leukemia (n = 25), undergoing chemotherapy, including those undergoing allogeneic hematopoietic stem cell transplantation at the Department of Pediatrics, Jena University Hospital, Jena, Germany. PAP regimens included L-AMB (1 mg/kg/day or 3 mg/kg twice weekly, intravenously), posaconazole (100-300 mg/day, according to blood concentration, orally or intravenously) and micafungin (1 mg/kg/day or 3 mg/kg twice weekly, intravenously). Thirty-four patients (35.8%) received L-AMB, 37 patients (38.9%) received posaconazole, and 24 patients (25.3%) received micafungin. Patients with a history of IFD or concurrent or changing PAP were excluded. The primary endpoint was the occurrence of breakthrough IFD, while secondary endpoint included IFD-free survival. Statistical analyses were performed using Kaplan-Meier survival analysis, Gray's test and Cox regression to evaluate IFD-free survival.
The overall incidence of IFD was 14.7% (14 of 95 patients). IFD developed in 10 of 33 patients (29.4%) receiving L-AMB, in 4 of 38 (10.8%) patients receiving posaconazole and in none of the patients receiving micafungin. IFD-free survival was 70.6% in the L-AMB group, 89.2% in the posaconazole group and 100% in the micafungin group (p = 0.005, log-rank test). Significant differences were also observed in the cumulative incidences of breakthrough IFDs (p = 0.006) assessed by Gray's test. In multivariate Cox analysis, dichotomized prophylaxis regimes (posaconazole or micafungin vs. L-AMB) were independently associated with a reduced risk of IFD (HR = 0.244; 95% CI 0.076-0.777; p = 0.017). Age ≥ 10 years predicted inferior IFD-free survival (HR = 3.665; 95% CI 1.224-10.980; p = 0.020).
We found a significant difference in efficacy between the three antifungal prophylaxis regimens. In our study, micafungin achieved the lowest IFD breakthrough rate. However, multicenter clinical studies would be needed to confirm the results.
侵袭性真菌病（IFD）是包括急性白血病在内的血液系统恶性肿瘤患儿发病和死亡的重要原因。我们的研究旨在比较脂质体两性霉素B（L-AMB）、泊沙康唑或米卡芬净作为急性白血病患儿原发性抗真菌预防（PAP）的疗效。
这项回顾性观察研究纳入了95例急性淋巴细胞白血病（n = 70）或急性髓细胞白血病（n = 25）且正在接受化疗的儿科患者，包括在德国耶拿大学医院儿科接受异基因造血干细胞移植的患者。PAP方案包括L-AMB（1mg/kg/天或3mg/kg每周两次，静脉注射）、泊沙康唑（100 - 300mg/天，根据血药浓度，口服或静脉注射）和米卡芬净（1mg/kg/天或3mg/kg每周两次，静脉注射）。34例患者（35.8%）接受L-AMB，37例患者（38.9%）接受泊沙康唑，24例患者（25.3%）接受米卡芬净。排除有IFD病史或同时进行或更改PAP的患者。主要终点是突破性IFD的发生，次要终点包括无IFD生存期。采用Kaplan-Meier生存分析、Gray检验和Cox回归进行统计分析，以评估无IFD生存期。
IFD的总体发生率为14.7%（95例患者中的14例）。接受L-AMB的33例患者中有10例（29.4%）发生IFD，接受泊沙康唑的38例患者中有4例（10.8%）发生IFD，接受米卡芬净的患者中无一例发生IFD。L-AMB组的无IFD生存期为70.6%，泊沙康唑组为89.2%，米卡芬净组为100%（p = 0.005，对数秩检验）。通过Gray检验评估的突破性IFD的累积发生率也观察到显著差异（p = 0.006）。在多变量Cox分析中，二分法预防方案（泊沙康唑或米卡芬净与L-AMB）与IFD风险降低独立相关（HR = 0.244；95%CI 0.076 - 0.777；p = 0.017）。年龄≥10岁预示无IFD生存期较差（HR = 3.665；95%CI 1.224 - 10.980；p = 0.020）。
我们发现三种抗真菌预防方案在疗效上存在显著差异。在我们的研究中，米卡芬净的IFD突破率最低。然而，需要多中心临床研究来证实这些结果。
