Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients

With compromised bone marrow function, patients with aplastic anemia (AA) and/and hypoplastic myelodysplastic syndrome (hMDS) are at an increased risk of invasive fungal infection. Moreover, the use of antithyocyte globulin (ATG), a part of standard first line treatment for AA/hMDS, increases the risk of fungal infection due to its antilymophocytic effects. It has been reported that fungal infection occurs most often in the first few weeks after initiation of ATG treatment, and the reported incidence of fungal infection overall varies from 9\~80% for AA/hMDS patients. Among them invasive fungal infection accounts for 6-20% depending on reports. Such being the case, antifungal prophylaxis is recommended for AA/hMDS patients undergoing ATG treatment. More specifically, the British Committee for Standards in Haematology (BCSH) recognized the threat of increased invasive fungal infections in AA patients, and stipulated the use of mould (aspergillus) active azole, "preferably itraconazole or posaconazole" as prophylaxis. Unfortunately however, though many centers have adopted their own practice schemes, and antifungals have been routinely administered in the context of investigational regimens, there is no consensus as to which antifungal agent should be used. Considering Aspergillus sp has remained the most common fungal isolate in AA patients for the past 20 years, it is only rational that an antifungal agent with broad spectrum, covering both yeast and fungi, be used in this context. Posaconazole, a triazole antifungal agent, not only has a broad coverage spectrum but also associated with predictable and reliable systemic bioavailability. Also for patients, once daily dosage is both pragmatic and convenient. According to meta-analyses of prophylactic antifungal agents use (published in 2007), fluconazole diminished the risk of fungal related mortality compared to placebo (RR 0.49, 95% CI: 0.32-0.75, P=0.0009). More importantly, when compared to fluconazole, posaconazole prophylaxis yielded even lesser fungal related mortality and significantly decreased invasive fungal infection rate. Considering the fact that posaconazole is already being used for acute myeloid leukemia (AML) and myelodysplastic syndromes patients undergoing induction treatment, it is only natural that posaconazole be used for AA/hMDS patients, who are at higher risk of developing invasive fungal infection compared to AML.