Posaconazole prophylaxis during induction therapy of patients with acute lymphoblastic leukaemia

Abstract

Novel treatment schedules of induction therapy for acute lympoblastic leukaemia (ALL) use combinations of immunosuppressive and cytotoxic drugs that are associated with neutropenia and acquisition of invasive fungal infections. It has been described that posaconazole, a triazole antifungal drug, is active against a variety of Candida and Aspergillus species in vitro. Moreover, large clinical trials using posaconazole in severely immunosuppressed patients provided data on efficacy against Aspergillus in vivo. As patients with ALL are also affected by difficult-to-treat Aspergillus infections, we conducted a pilot study to prove the safety of posaconazole in patients undergoing intensified induction phase treatment. We report on eight patients receiving prophylactic (200 mg t.i.d.) dose of posaconazole and demonstrate good tolerability of the drug. The most obvious side effect was liver toxicity as defined by abnormal serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase and bilirubin levels (<CTC grade 3) documented in three of eight patients. However, side effects were not life-threatening and appeared without clear relationship to posaconazole applications. During the study, one patient developed possible aspergillosis of the lung. Therefore, the observations indicate a favourable toxicity profile of posaconazole in ALL therapy. Efficacy of the drug has to be further validated in prospective clinical trials.