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Outcome in Pediatric Patients with a History of Fungal Disease Prior to Allogeneic Stem Cell Transplant
Patients and Methods: Data was collected on 152 pediatric patients between the ages of 0-21 years who received an allogeneic stem cell transplant for any diagnosis at Stanford University between 2005 and 2012. Twenty five of these patients had a history of fungal disease prior to transplant. All of these patients received secondary antifungal prophylaxis, although the specific medication used and dosing was at the discretion of the treating physician. Patients were analyzed regarding mortality and rates of secondary fungal disease. Fungal disease was classified as proven, probable, or possible invasive fungal disease based on the EORTC/MSG classification.
Results: Only 2 of the 25 patients with prior fungal disease developed probable or proven invasive fungal disease after transplant. The first patient was an 18 year old male with relapsed AML who was diagnosed with fungal pneumonia (culture positive for aspergillus and candida at an outside hospital) three years prior to transplant. He subsequently developed recurrent fungal pneumonia (culture positive for 3 different species of aspergillus and non candida albicans yeast) approximately 1 year after transplant. He was non compliant with his antifungal prophylaxis after discharge. This patient ultimately died of his fungal infection.
The second patient was a 16 year old male with relapsed AML who was diagnosed with pulmonary fungal infection on pre-transplant evaluation. He underwent a lobectomy prior to transplant with fungal hyphae visualized on pathology, although cultures were negative. He was maintained on twice weekly liposomal amphotericin and daily caspofungin after discharge. Despite this prophylaxis, he developed pulmonary and ocular fungal disease with a positive aspergillus galactomannan 8 months after transplant. This patient ultimately died secondary to infection and chronic GVHD.
Of the remaining 23 patients with a history of fungal disease prior to transplant, 13 were diagnosed based on pulmonary nodules only, 4 were diagnosed based on abnormal imaging findings in multiple organs, and the remaining 6 were diagnosed by microbiology or histologic findings. These patients received prophylaxis as follows: 5 voriconazole alone, 8 amphotericin alone and 10 a combination of antifungals. Mortality in this group was 26%, and this was not significantly different from the mortality in patients with no history of fungal disease prior to transplant.
Conclusions: With appropriate treatment and secondary prophylaxis, it is possible for patients with a history of fungal disease to undergo allogeneic stem cell transplant without a recurrence of their fungal disease or an increase in mortality rate.