Risk-Adapted Anti-Mould Prophylaxis Improves Supportive Care in Childhood Leukemia Patients

BACKGROUND: Prophylaxis of invasive fungal infections in children treated for malignant hematologic disease has traditionally been based on the widespread use of fluconazole. With the awareness of increasing rates of invasive mould infections, new agents have been developed and offered to patients at highest risk.

METHODS: We compared the tolerance and outcome of different antifungal prophylaxis in 198 childhood patients treated for acute myeloid and lymphoblastic leukemia in a pediatric cancer center. Until 2011 antifungal prophylaxis with fluconazole was offered to all patients, resulting in 15.2-19.4% of invasive mould infections. As the burden of fungal infections was restricted to high risk patients only (i.e. acute myeloid leukemia, leukemia relapse, high risk acute lymphoblastic leukemia and patients after stem cell transplant) and no infection with candida was registered, antifungal prophylaxis was replaced with liposomal amphotericin and offered to this particular patient group.

RESULTS: Liposomal amphotericin was well tolerated; there was no occurrence of infusion-related reaction and/or glomerular-associated nephrotoxicity. The development of vincristine-induced neurotoxicity was significantly reduced, as stool frequency was increased up to 38% in patients treated with liposomal amphotericin (p = 0.024). Importantly, there was a marked shift in the percentage of patients with severe constipation (15.5% versus 4.2%, fluconazole versus liposomal amphotericin respectively, p = 0.010). Notably, with limitation of prophylactic treatment to high risk patients a major group of patients did not receive any antifungal prophylaxis (48.81%) and most importantly, the occurrence of invasive fungal infection was completely prevented (p = 0.021). In comparison, 10 patients in the fluconazole group developed proven invasive pulmonary infections. Of these, 6 patients developed disseminated disease, and 4 patients died. Aspergillus was isolated in 40% and rhizopus in 30% of biopsy specimens.

CONCLUSION: Polyene prophylaxis offers effective antifungal activity with improved tolerability compared to older agents. The potential impact of this treatment should be included in current prophylaxis guidelines of antileukemic treatment.