In children with acute lymphoblastic leukemia (ALL), risk groups for invasive fungal disease (IFD) with need for antifungal prophylaxis are not well characterized, and with the advent of new antifungal compounds, current data on outcome are scarce. Prospectively captured serious adverse event reports of children enrolled in the international, multi-center clinical trial AIEOP-BFM ALL2009 were screened for proven/probable IFD, defined according to the updated EORTC/MSG consensus definitions. In a total of 6136 children (median age 5.2 years), 224 proven/probable IFDs (65 yeast and 159 mold) were reported. By logistic regression, the risk for proven/probable IFDs was significantly increased in children ≥12 years and those with a blast count ≥10% in the bone marrow on day 15 (P < 0.0001 each). Proven/probable IFDs had a 6-week and 12-week mortality of 10.7% and 11.2%, respectively. In the multivariate analysis, the hazard ratio for event-free and overall survival was significantly increased for proven/probable IFD, age ≥12 years, and insufficient response to therapy (P < 0.001, each). Our data define older children with ALL and those with insufficient treatment-response at high risk for IFD. As we show that IFD is an independent risk factor for event-free and overall survival, these patients may benefit from targeted antifungal prophylaxis.

Clinica Pediatrica and Centro Ricerca Tettamanti Università di Milano Bicocca Fondazione MBBM S Gerardo Hospital Monza Italy

Czech Working Group for Pediatric Hematology Prague Czech Republic

Department of Pediatric Hematology Oncology Hannover Medical School Hannover Germany

Department of Pediatric Hematology Oncology University Hospital Motol 2nd Faculty of Medicine Charles University Prague Czech Republic

Infectious Disease Research Program Department of Pediatric Hematology and Oncology and Center for Bone Marrow Transplantation University Children's Hospital Münster Münster Germany

Paediatric Haematology Oncology Department of Mother and Child Azienda Ospedaliera Universitaria Integrata Verona Italy

Pediatric Hematology and Oncology Hospital for Children and Adolescents Johann Wolfgang Goethe University Frankfurt Germany

Pediatric Hematology Oncology Schneider Children's Medical Center Petah Tikva and Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

Pediatrics University Hospital Schleswig Holstein Campus Kiel Kiel Germany

St Anna Kinderspital and Children's Cancer Research Institute Vienna Austria

Sydney Children's Hospital Randwick NSW Australia

University Children's Hospital Zurich Zurich Switzerland

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