Changing face of invasive Aspergillus infections in children undergoing haematopoietic stem cell transplantation: a single centre observational study over 20 years

Lynne Ball*, Hanny Bakker Steenveld, Clementien Vermont

Author address: 

Leiden, NL


Background: We previously reported (EBMT 2003) that in our pediatric transplant unit (1993 to 2002), the incidence of proven invasive aspergillus (IA) was low, occurred early in the transplant period and survival was compromised in those receiving serotherapy. Since then, Dutch pediatric oncology recommendations for screening, drug therapeutic monitoring (DTM) and recognition of azole resistance has resulted in changes in management strategy. 
Methods: We reviewed data from January 2003 to July 2012 and compared the results to our previous study, to determine whether recent strategies have altered outcome for children with IA undergoing hematopoietic stem cell transplantation (HSCT). 
Results: The comparative data sets for children undergoing HSCT in our unit with proven IA are summarized in Table 1. 
Although infection rate remains low in our unit we have noted a dramatic change in the timing of occurrence of documented IA compared to our earlier observations (median of 66 days v 13 days resp.). Children with late onset IA (>50days post ) were more likely to have undergone unrelated donor HSCT and have associated graft dysfunction (i.e. failure or delayed engraftment). In contrast to earlier observations, survival is no longer limited to those children undergoing identical related bone marrow transplantation. 
Two patients received preemptive granulocyte transfusions (GT) to facilitate a successful transplant, a treatment not readily available in the previous era. Three patients developed proven azole resistant IA and as testing was not available in the previous study no comparisons can be made. DTM revealed the majority of children required dose adjustment to achieve therapeutic prophylactic doses of either itraconaozole of voriconazole. Again no comparison can be made with earlier observations. 
Conclusion: Proven IA remains an uncommon event in our unit and mortality is low (2%). Changes in clinical practice have seemingly affected the timing of presentation. Patients with leukemia and aplastic conditions receiving azole prophylaxis prior to referral, with dose optimization by DTM, may have reduced early HSCT infection. Our study shows that graft dysfunction is a risk factor together with GVHD for the occurrence of IA. We recommend close microbiological monitoring and prophylaxis with rigorous DTM control in this specific post transplant group. Azole resistance and its impact on survival remain unclear and is presently being closely monitored on a national basis. 


Full conference title: 

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