Invasive Fungal Diseases in Pediatric Acute Lymphoblastic Leukemia Patients Receiving Mold-Active Primary Antifungal Prophylaxis

Acute lymphoblastic leukemia (ALL) has a very high survival rate in children. However, invasive fungal diseases (IFDs) remain important causes of morbidity and mortality in these patients. This study aimed to evaluate the prevalence, risk factors, etiology, and outcomes of IFDs in children with de novo ALL and to assess the effects of primary mold-active antifungal prophylaxis on occurrence and ALL outcomes. This retrospective study included children diagnosed with ALL between 2006 and 2022. Patients diagnosed between 2013 and 2022 received primary antifungal prophylaxis (PAP) with voriconazole and constituted the antifungal prophylaxis (AFP) group. Patients treated at our institution before 2013 did not receive PAP and were classified as the no-AFP group. A total of 278 patients were included in the study, of whom 184 (66.2%) were in the AFP group. In the no-AFP group, the prevalence of proven and probable IFDs was 12.8% each; in the AFP group, these rates decreased to 2.2% for proven IFD (P<0.001, OR: 0.417 [95% CI: 0.299-0.583]) and 1.6% for probable IFD in the AFP group (P=0.0001, OR: 0.390 [95% CI: 0.286-0.532]). No increase in infections caused by rare fungal pathogens was observed in the AFP group. The estimated 5-year OS rates were 90.2% for patients without IFD and 70.0%, 68.2%, and 66.0% for patients with possible, probable, and proven IFD, respectively (global log-rank P=0.000041). Similarly, the 5-year EFS rates were 87.9% in the no-IFD group, compared to 70.0%, 54.5%, and 60.0% in the possible, probable, and proven IFD groups, respectively (global log-rank P=0.000001). Mold-active prophylaxis reduced the prevalence of proven and probable IFDs in this cohort without increasing infections caused by rare fungal pathogens.