Patients with severe acute or chronic GVHD undergoing intense immunosuppressive therapy have a high risk of severe opportunistic infections frequently determining outcome. Invasive fungal infections (IFI), especially invasive aspergillosis, are frequent and often fatal in such patients. In recent years substantial progress has been made in prophylaxis and treatment of IFI. Posaconazole given prophylactically in patients with severe GVHD has been shown to decrease the incidence of IFI and death attributed to fungal disease in a prospective randomized study. We retrospectovely analyzed whether posaconazol prophylaxis was effective in reducing fungal infections in a large allogeneic program.
From January 2008 to July 2011 we treated 80 episodes of either acute GVHD grade II-IV or chronic GVHD in 53 patients who received prednisolone at doses of more than 0.5 mg/kg BW. The median age was 52.5 years (19.8 - 73.7 years), the median duration of corticosteroid application was 44.5 days (3 - 308 days), the median duration of inpatient treatment was 19.2 days (4 – 98 days) Our institutional standard operating procedures recommend the use of prophylactic posaconazole (200 mg tid) which was given in 52 of 80 cases. In 28 cases we decided against posaconazole because a less intensive immuno-supression was anticipated at start of prednisolon treatment. In fact this group showed showed a shorter duration of treatment(median 36 vs 46 days) and a lower number of patients with of prolonged usage ( > 44 days) of prednisolone (39 vs 56%) as compared to the other patients . In 16 of 52 cases (30.8%) with posaconazole prophylaxis an interventional treatment with either caspofungin ( 7 cases) or voriconazole (9 cases) was started. FUO / sepsis were the main reasons to start treatment in 8 cases, pneumonia was the leading condition in other 8 cases. Two patients received second- line treatment ( 1 case caspofungin after voriconazole, 1 case voriconazole after caspofungin). In 5 out of 52 cases (9.6%) the EORTC criteria of a possible IFI were fulfilled. There were no cases of a probable or proven IFI. There was no death attributable to IFI. In patients with severe GVHD and intensive immunosuppression, prophylaxis of IFI by posaconazole results in a very low specific morbidity and mortality
Full conference title:
- EBMT 39th (2013)