Abstract

Invasive fungal diseases (IFD) represent an important cause of treatment failure in adults with acute leukemia (A-Leuk). Because of leukemia's heterogeneity, the risk for IFD is highly variable. We therefore apply a risk-adapted antifungal strategy with strong emphasis on pretreatment and day 15 post-treatment to allow earlier and more individualized interventions. We determine pretreatment risks for IFDs based on four factors: 1) host fitness for standard therapy; i.e. 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 into high, intermediate or low risk for IFD and apply risk-adapted antifungal strategies including primary or secondary prophylaxis, diagnostic-based preemptive or empiric therapy. Prevention of IFD 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.

Marcio Nucci and Elias Anaissie,
Blood 2014 :blood-2014-04-516211; doi: https://doi.org/10.1182/blood-2014-04-516211