Discussion
IFD, neutropenia, proven/probable IFD, cancer, AML, ALL
ACUTE MYELOID LEUKEMIA, NEUTROPENIA, CANCER, PEDIATRIC ALL, AML, INVASIVE ASPERGILLOSIS
In the prospective, randomized multi-international clinical trial AIEOP-BFM ALL2009 enrolling 6136 children with ALL, the reported overall incidence of proven/probable IFD and proven/probable/possible IFD was 3.8% and 6.2%, respectively, but was significantly higher in various subgroups, e.g., in older children and adolescents or in patients with insufficient early treatment response. The reported incidence rates of IFD in children with ALL vary widely across previous studies with rates reaching from 3.8% to up to 24% [Unexpectedly, we found in a subgroup of patients a significant correlation between the number of neutrophils at the time of diagnosis of ALL and the risk for IFD. This is in contrast to children with acute myeloid leukemia (AML), in which neutropenia at the start of chemotherapy was independently associated with IFD [In an early report on invasive aspergillosis in 66 children with cancer published in the 1990ies, mortality after 1 month was 48%, and was 75% after 2 months [The strength of our study is the fact that the analysis is based on the data of a contemporary multi-centered international randomized controlled clinical trial. We included the largest dataset on IFD in pediatric ALL to date, and the data quality is extremely high due to the fact that SAEs were prospectively collected and monitored in a systematic way. In addition, all potentially relevant SAEs were independently evaluated by two experts, based on the revised and updated definitions of IFD from the EORTC/MSG consensus group, which added the widely used 