Posaconazole as Prophylaxis in Immunocompromised Patients: A Single Center Experience

Abstract

Efficacy of posaconazole was recently demonstrated in the prevention of invasive fungal infections (IFI) in recipients of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with GVHD and in patients undergoing intensive chemotherapy for acute myelogenous leukemia or myelodysplastic syndromes.Between Jan 2007 and April 2008, 54 patients had received posaconazole prophylaxis (200 mg t.i.d orally) either during induction chemotherapy (33 pts) or because of GVHD (25 pts). Four patients belong to the two subgroups. We analyze these two subgroups separately. IFI were defined as possible/probable/proven according to EORTC/MSG criteria. Prophylaxis with posaconazole was performed to 33 patients undergoing induction chemotherapy (29 AML, 3 MDS, 1 aplastic anemia), (19F/14M), median age 67 years ( range 21 – 81). The median duration of neutropenia (ANC< 500 cells/mm3 ) was 39 days (range10 – 278 days). Median duration of posaconazole prophylaxis was 27 days (range 4 – 203 days), early discontinuation of prophylaxis was observed in 20 patients because of progression to IFI in 5 cases, empirical antifungal therapy for persistent fever (11 cases), mucositis (3 cases) and hepatic toxicity (1 case). Possible or probable IFI was diagnosed in 5/33 (14%) patients (3 possible and 2 probable pulmonary aspergillosis). Five deaths were occurred, only one was related to the IFI, other causes of death were intercurrent disease in 3 patients and one septic choc. Twenty five patients with GVHD treated with intensive immunosuppressive therapy had received posaconazole prophylaxis (13F/12M), median age 52 years (range21– 70), one patient had a prior diagnosis of IFI and was in complete resolution. RIC allo-HSCT was performed to 12 patients,10 sibling donors,14 MUD, one patient received umbilical cord blood transplantation. Acute GVHD grade II to IV and chronic extensive GVHD were reported in 16 and 9 patients respectively. All patients had received high dose corticosteroids (0.5 to 2 mg/Kg/d), the majority of them (21) had two or more immunosuppressive agents. The median duration of posaconazole prophylaxis was 110 days (range 19 days - 10 months), 6 patients are still receiving prophylaxis, 4 premature discontinuations due to hepatic toxicity in one case, progression to IFI in 2 cases and diet because of severe digestive GVHD in one case. Two patients (8%) developed IFI ( 1 possible and 1 probable pulmonary aspergillosis) during prophylaxis period. One patient died from IFI. IFI-unrelated death occurred in 5/25 (20%) patients.Conclusions: We observed 6% (2/33) probable/proven IFI in AML patients undergoing intensive chemotherapy and 4% (1/25) in GVHD patients witch is comparable to the incidence reported in recent studies (Oliver et al., NEJM 2007; 356:348–59/Andrew et al., NEJM 2007; 356:335–47). These results suggest that posaconazole prophylaxis is effective in reducing the incidence of IFI in this high risk population.