Invasive Pilzinfektionen nach allogener Stammzelltransplantation – eine Untersuchung möglicher Risikofaktoren und der durchgeführten Prophylaxestrategien am Universitätsklinikum Marburg

Invasive fungal infections are one of the most frightened complications after allogeneic stem cell transplantation and associated with high mortality rates. Fluconazole has become standard of care in the medical prophylaxis. One of the main risk factors for developing an invasive fungal infection after allogeneic stem cell transplantation is a severe GvHD. In these patients a mold-effective prophylaxis with Posaconazole is recommended instead. Also other factors can help to prevent invasive fungal infections, for example the use of HEPA filtration. At the University Hospital in Marburg every patient that undergoes allogeneic stem cell transplantation or requires further hospitalization is treated in rooms that are fully equipped with HEPA filtration. Fluconazole is used as standard prophylaxis even in patients with severe GvHD. An early CT scan is performed if there is any clinical sign of developing an invasive fungal infection. If there is any clinical suspicion or any imaging hint of an invasive fungal infection the prophylaxis is switched immediately to a mold-effective therapy with Voriconazole or Posaconazole. Only in patients with a history of prior invasive fungal infection a mold-effective prophylaxis with Voriconazole or Posaconazole is continued during and after allogeneic stem cell transplantation. The aim of the study was to evaluate the incidence and mortality of invasive fungal infections using the described prophylactic strategy. In addition possible risk factors for developing an invasive fungal infection should be analysed. In this retrospective cohort study 290 patients were included who underwent allogeneic stem cell transplantation at the University Hospital in Marburg from May 2002 till August 2011. There were no exclusion criteria. We chose an observation period of 2 years after allogeneic stem cell transplantation. Primary end point was the occurence of an invasive fungal infection. According to the definitions of the EORTC/MSG group invasive fungal infections were classified as “possible”, “probable” or “proven”. The main focus was set on CT scans. Other end points were overall survival and mortality due to IFI. For further analysis patients were subdivided in a standard group and a high risk group. High risk patients were those with an acute GvHD II-IV° or an extensive chronic GvHD under immunosuppressive therapy. In total 90 patients met the criteria for the high risk group. Statistical analyses were performed by using IBM SPSS Statistics, Version 22.0. Univariate analyses of possible risk factors were performed by the Logrank test, multivariate analyses were done by Cox regression. In all patients the incidence of invasive fungal infection was 8,97% (n=26/290). Mortality rate of invasive fungal infection was 3,85% (n=1/26). Within the high risk group the incidence of invasive fungal infection was 7,78% (n=7/90). No high risk patient died due to the invasive fungal infection. In the entire population a history of prior invasive fungal infection could be identified as significant risk factor for developing an invasive fungal infection after allogeneic stem cell transplantation (25,81% vs. 6,95%; p<0,005). The significance could be confirmed in the multivariate analysis (HR=5,298; p=0,001). Within the high risk group a prior history of invasive fungal infection could not be seen as significant risk factor. With regard to the choice of prophylaxis (Fluconazole vs mold-effective prophylaxis) after allogeneic stem cell transplantation no significant difference could be shown neither in all patients (10,0% vs. 11,67%; p=0,433) nor in the high risk group (6,58% vs. 14,29%; p=0,094). Also no other tested risk factor showed a significant impact on developing an invasive fungal infection after allogeneic stem cell transplantation. In conclusion this retrospective study could report a low incidence and a very low mortality rate of invasive fungal infections at the University Hospital in Marburg. The described prophylactic strategy is feasible in a setting of stringent hygiene measures including HEPA filtration and carefully monitoring of clinical signs of developing an invasive fungal infection that results in early CT scans and switching to a mold-effective therapy. Patients with a prior history of invasive fungal infection should be treated with a mold-effective prophylaxis to prevent an increased incidence of invasive fungal infections after allogeneic stem cell transplantation.