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@ARTICLE{Gottschlich:304095,
author = {A. S. Gottschlich and J. Ernst and T. Milde$^*$ and B.
Gruhn},
title = {{C}omparative study of liposomal amphotericin {B},
posaconazole, and micafungin for primary antifungal
prophylaxis in pediatric patients with acute leukemia.},
journal = {Journal of cancer research and clinical oncology},
volume = {151},
number = {8},
issn = {0301-1585},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2025-01763},
pages = {235},
year = {2025},
abstract = {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.},
keywords = {Humans / Micafungin: administration $\&$ dosage / Male /
Female / Child / Antifungal Agents: therapeutic use /
Antifungal Agents: administration $\&$ dosage /
Retrospective Studies / Triazoles: administration $\&$
dosage / Triazoles: therapeutic use / Amphotericin B:
administration $\&$ dosage / Amphotericin B: therapeutic use
/ Child, Preschool / Adolescent / Precursor Cell
Lymphoblastic Leukemia-Lymphoma: complications / Precursor
Cell Lymphoblastic Leukemia-Lymphoma: drug therapy /
Leukemia, Myeloid, Acute: complications / Leukemia, Myeloid,
Acute: drug therapy / Infant / Mycoses: prevention $\&$
control / Invasive Fungal Infections: prevention $\&$
control / Acute leukemia (Other) / Invasive fungal disease
(Other) / Liposomal amphotericin B (Other) / Micafungin
(Other) / Pediatric (Other) / Posaconazole (Other) / Primary
antifungal prophylaxis (Other) / Micafungin (NLM Chemicals)
/ Antifungal Agents (NLM Chemicals) / posaconazole (NLM
Chemicals) / Triazoles (NLM Chemicals) / Amphotericin B (NLM
Chemicals) / liposomal amphotericin B (NLM Chemicals)},
cin = {B310},
ddc = {610},
cid = {I:(DE-He78)B310-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40848057},
doi = {10.1007/s00432-025-06289-5},
url = {https://inrepo02.dkfz.de/record/304095},
}