Risk stratification accompanied by liposomal amphotericin-B (L-AMB) antifungal prophylaxis reduced the risk of potentially life-threatening complications compared with fluconazole prophylaxis in pediatric patients with acute leukemia, according to the results of a study published in the British Journal of Haematology.
The investigators conducted a single-center, retrospective study to compare tolerability and outcomes of different antifungal prophylaxis strategies during induction therapy. Study participants included 198 pediatric patients (median age, 5.3 years; 55.6% male) with acute leukemia undergoing induction therapies (including various established guidelines for the prevention and management of invasive fungal infections [IFIs]) at the Department of Pediatrics of the Medical University of Innsbruck in Austria between January 2000 and December 2018. The majority of patients were treated for acute lymphoblastic leukemia (ALL); 68.2% were treated for B-ALL and 15.7% were treated for T-ALL, while 14.1% of patients were treated for acute myeloid leukemia.
After 2010, the department shifted their antifungal prophylaxis strategy and considered prophylaxis only for high-risk patients. This allowed the investigators to divide the patient data into 2 time-based cohorts (2000-2010 and 2011-2018) that received different antifungal prophylaxis according to risk stratification.
Between 2000 and 2010, most children received antifungal prophylaxis with azole (89.7%), which was mainly fluconazole. Half of the patients treated from 2011 to 2018, did not receive antifungal prophylaxis; however, among those who did receive prophylaxis, high-risk patients were treated with L-AMB (36.6%).
Vincristine-induced neurotoxicity, which may be exacerbated by interaction with azoles, including fluconazole, was measured as the percentage of patients with severe constipation, and it was significantly lower in the 2011 to 2018 cohort compared with the 2000 to 2010 cohort (15.4% vs 3.7%, respectively; P =.01).
In the 2000 to 2010 cohort, 10 patients developed IFIs, typically Aspergillus species (9/10), which are naturally resistant to fluconazole. After risk adaption in 2011, no IFIs developed in the 2011 to 2018 cohort (P =.007).
The authors noted that newer azoles (itraconazole, voriconazole, and posaconazole) offer potent antifungal activity, even against Aspergillus; however, their interactions with vincristine remain a concern. Therefore, they suggest that risk stratification and selective administration of L-AMB in patients with carefully defined high-risk leukemia is a safe and efficacious approach for antifungal prophylaxis.
The primary limitations of the study were its retrospective design and variation in patient management.
“Our risk-adapted therapy works efficiently to prevent antifungal prophylaxis and reduces neurotoxicity,” wrote the authors. “The potential impact of our risk-adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia.”
Meryk A, Kropshofer G, Hutter J, et al. Benefits of risk‐adapted and mould‐specific antifungal prophylaxis in childhood leukaemia [published online July 4, 2020]. Br J Haematol. doi: 10.1111/bjh.16931