Abstract
Background Fungal infection is common in acute lymphocytic leukemia (ALL), which can lead to significant mortality and morbidity. Our aim is to compare the efficacy of antifungal prophylaxis using fluconazole 400 mg once daily versus amphotericin B lipid complex 2.5 mg/kg three times per week in adult patients with ALL during the neutropenic nadir who received hyper-CVAD as part of their chemotherapy regimen.
Methods This was a retrospective, cohort chart review study conducted in eligible patients with ALL who received a hyper-CVAD- based chemotherapy regimen between 1 January 2007 and 31 December 2016 at KAMC, Jeddah. We included patients with ALL aged older than 14 years who completed at least one course of hyper-CVAD and received antifungal prophylaxis. We excluded patients who received the BFM regimen. Data were collected using a hospital information system. The primary endpoint was the incidence of fungal infection, which was assessed using microbiology data and imaging studies for radiological evidence of fungal infections. The secondary endpoints were to assess QTc prolongation in Philadelphia-positive ALL that is associated with fluconazole use in combination with tyrosine kinase inhibitor, and lastly the cost impact based on the type of antifungal prophylaxis used.
Results A total of 105 cycles of hyper-CVAD were reviewed. In 70 cycles, fluconazole was used as antifungal prophylaxis (n= 70) and in 35 cycles amphotericin B lipid complex was used (n=35) as antifungal prophylaxis. Microbiologically documented fungal infection was found in two of 70 cycles in the fluconazole group and radiologically documented fungal infection was found in one patient in the fluconazole group. QTc prolongation was observed in 12 cycles. In nine of 12 cycles, events of QTc prolongation were observed during the study, fluconazole was used as antifungal prophylaxis, and patients were on tyrosine kinase inhibitor. In three of 12 cycles, events of QTc prolongation were observed during the study, amphotericin B lipid complex was used as antifungal prophylaxis, and patients were on tyrosine kinase inhibitor.
Conclusion Fluconazole is considered as standard antifungal prophylaxis in patients with ALL with acceptable safety profiles. Fluconazole had comparable efficacy to amphotericin lipid complex. Fluconazole may cause QTc prolongation when used in combination with tyrosine kinase inhibitors and patients need to be monitored more closely when this combination is used in those with Philadelphia-positive ALL.
