How we treat invasive fungal diseases in patients with acute leukemia: the importance of an individualized approach

Invasive fungal diseases (IFDs) represent an important cause of treatment failure in adults with acute leukemia. Because of leukemia's heterogeneity, the risk for IFDs is highly variable. We therefore apply a risk-adapted antifungal strategy with strong emphasis on pretreatment and day-15 posttreatment to allow earlier and more individualized interventions. We determine pretreatment risks for IFDs based on 4 factors: (1) host fitness for standard therapy (ie, fit, unfit, or frail); (2) leukemia resistance (high vs low probability of achieving complete remission [CR]); (3) anticipated treatment-related toxicity such as neutropenia, mucositis, and steroid-induced immunosuppression; and (4) patient exposure to opportunistic fungi. Accordingly, we stratify patients as high, intermediate, or low risk for IFDs and apply risk-adapted antifungal strategies, including primary or secondary prophylaxis and diagnostic-based preemptive or empiric therapy. Prevention of IFDs also relies on optimizing organ function, decreasing exposure to opportunistic fungi, and improving net state of immunosuppression with use of better-tolerated and investigational agents for unfit patients and those with adverse leukemia biology. Novel targeted and safe therapies that can achieve higher rates of sustained CR among patients with adverse genetics offer the best promise for reducing the burden of IFDs in these patients.