Galactomannan antigen in children undergoing allogeneic stem cell transplantation and antifungal prophylaxis with voriconazole

Diana Buenasmañanas*, José Ramón Molina, Antonia Rodríguez-Villa, Carmen Martínez-Losada, Estefanía García-Torres, Lara María Gómez-García, Rafael Rojas, Carmen Martín, Pedro Gómez

Author address: 

Córdoba, ES


Introduction: Invasive Fungal Disease (IFD) remains a major cause of morbidity and mortality in children undergoing Allogeneic Hematopoietic Stem Cell Transplantation (allo-SCT). Serum galactomannan antigen (GM) detection is a useful tool for the diagnosis of invasive aspergillosis in high-risk patients, although in children the promising results seen in adults have not been clearly confirmed. In this sense, we have analyzed in this prospective study our experience in pediatric patients undergoing allo-SCT and who received antifungal prophylaxis with a mold active drug as voriconazole 
Patients Aan Methods: A total of 59 children <18 years were enrolled in this study from Jun-2006 to Mar-2012. Median age was 9 years (range: 2-17). All patients received voriconazole from day -1 at a dose of 5 mg/kg/12 hours (n=13) or 7 mg/kg/12 hours (n=46) until a highest dose of 200 mg/12 hours. We consider neutropenic period from day 0 to one week after neutrophils recovery (>500/mm3). Proven or probable IFD was diagnosed according to EORTC/MSG criteria. The GM was measured twice weekly and was considered positive if the index value was >0.5 in two consecutive test or >0.8 in a single test. 
Results: Only two (3.4%) children developed IFD (probable aspergillosis) during neutropenia while on prophylaxis with voriconazol. In this series 51 (86.4%) patients completed successfully the prophylaxis during this period without adverse effects, no empirical or preemptive antifungal therapy neither IFD. A total of 4 (6.7%) receptors required empirical (n=2) or preemptive (n=2) antifungal therapy with amphotericin B once stopped voriconazole, one of them developed IFD. In 3 (5.1%) children was detected adverse effects due to voriconazole prophylaxis and needed a definitive withdrawal; these adverse effects were solved when voriconazole was discontinued. In this series a total of 299 GM test was performed. A total of 13 (22%) children presented positive GM test and only one of them developed IFD. Sensibility and specificity per patient GM test were 50% and 78.9%, respectively. Positive and negative predictive values were 7.6% and 97.8%, respectively. 
Conclusions: With a successfully prophylaxis rate of 86.4%, voriconazole is effective as antifungal prophylaxis in children undergoing allo-SCT during neutropenic period. GM test shows low sensitivity and specificity in our series, with a high rate of false positives. GM results in children should be cautiously analyzed in order to avoid precipitated decisions.


Full conference title: 

Annual Meeting of European Society for Blood and Marrow Transplantation
    • EBMT 39th (2013)