Incidence and Mortality of Invasive Fungal Disease in Pediatric Patients after Allogeneic Stem Cell Transplant

Objective: The goal of this retrospective study was to analyze the incidence and outcome of invasive fungal disease in a large cohort of pediatric patients after allogeneic stem cell transplant at Stanford University from 2005-2012 treated with modern antifungal prophylaxis.  In comparison with prior studies, this study is unique in including prophylaxis with voriconazole and dosing information on antifungal prophylaxis, as well as the prevalence of transaminitis in this population and relation to antifungal prophylaxis.

Patients and Methods: Data was analyzed for 152 pediatric patients between the ages of 0-21 years who received allogeneic stem cell transplantation for any diagnosis at Stanford University between 2005 and 2012.   Both related and unrelated donors were used, including bone marrow, cord blood, and peripheral blood stem cell sources.   All patients received antifungal prophylaxis, although the specific medication used and dosing was at the discretion of the treating physician.  Patients were categorized as having proven, probable, or possible fungal disease based on the EORTC/MSG classification.  Rates of invasive fungal disease and level of transaminitis were analyzed by type of antifungal prophylaxis as well as dosing in milligrams per kilogram.

Results: The overall mortality in this cohort was 29%.  Of those, 57% of the deaths were due to relapse, 20% due to infectious complications (3 fungal, 3 sepsis, 2 viral, 1 toxoplasmosis), 16% due to organ failure, and 7% due to GVHD.  Twenty five patients were diagnosed with fungal disease prior to transplant and these patients were excluded from this analysis.

In the 127 patients with no prior history of fungal disease, 60% were on fluconazole prophylaxis, 32% were on voriconazole, 7% were on micafungin or caspofungin and 2% were on amphotericin.  Nine of these patients subsequently developed proven or probable invasive fungal disease.  Patients who developed invasive fungal disease had a significantly higher mortality rate (67%) compared with those who did not (25%).  However, these two groups did not differ on type of antifungal prophylaxis, underlying diagnosis, donor source, product used or age.  There was no difference in level of transaminitis based on type of antifungal prophylaxis (voriconazole vs. fluconazole) or dose used in milligrams per kilogram.

Conclusions:  In those patients who develop invasive fungal disease after transplant, mortality has decreased over time but remains substantial at 67%.  This data did not support the use of one antifungal over another for prophylaxis of invasive fungal disease in pediatric patients.  Voriconazole and fluconazole caused similar levels of transaminitis.