Efficacy of antifungal prophylaxis with oral suspension posaconazole during induction chemotherapy of acute myeloid leukemia.

BACKGROUND

Severe infectious complications reflect a continuing problem in patients with acute myeloid leukemia (AML). Based on data from a randomized clinical trial demonstrating a reduction of proven and probable invasive fungal disease (IFD), posaconazole has been approved for prophylaxis of fungal infections in AML patients during induction chemotherapy. Nevertheless, recently published observational studies show contradictory results concerning the efficacy of posaconazole in this clinical setting. Furthermore, oral suspension posaconazole is associated with an unpredictable bioavailability that especially depends on nutritional factors or gastric pH value.

PATIENTS AND METHODS

We retrospectively analyzed the impact of posaconazole prophylaxis in 70 consecutively evaluable AML patients who underwent induction chemotherapy at a tertiary care hospital. The incidence of IFD classified as proven, probable or possible, antifungal therapy including empiric treatment in high-risk patients and tolerability of posaconazole were determined. In addition, important clinical cofactors such as co-treatment with proton pump inhibitors and risk factors for pneumonia were analyzed in this study.

RESULTS

We can demonstrate that posaconazole is well tolerated and had to be stopped in only six patients (8.6%). The overall incidence of IFD was 30% including two patients with proven (2.8%), four patients with probable (5.7%) and 15 patients with possible IFD (21.4%). Importantly, 24 out of 49 patients (49.0%) who did not fulfill the criteria of IFD received empiric antifungal therapy. Including patients classified as possible IFD, 39 of 70 patients (55.7%) underwent at least first-line antifungal treatment.

CONCLUSION

Our "real-life" data obtained from 70 AML patients after induction chemotherapy demonstrate the frequent necessity of systemic antifungal treatment despite prophylaxis with oral suspension posaconazole.