Original article
Invasive fungal infections in paediatric acute myeloid leukaemia
D. L. Johnston,
1
V. Lewis,
2
R. Yanofsky,
3
B. Gillmeister,
4
M. C. Ethier,
4
D. Mitchell,
5
S. Cellot,
6
D. Dix,
7
C. Portwine,
8
V. Price,
9
M. Silva,
10
S. Zelcer,
11
B. Michon,
12
L. Bowes,
13
K. Stobart,
14
J. Brossard,
15
J. Beyene
4,16
and L. Sung
4,17
1
Hematology Oncology, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada,
2
Hematology/Oncology/Transplant Program, Alberta Children’s
Hospital, Calgary, AB, Canada,
3
Hematology/Oncology, CancerCare Manitoba, Winnipeg, MB, Canada,
4
Child Health Evaluative Sciences, The Hospital for
Sick Children, Toronto, ON, Canada,
5
Hematology/Oncology, Montreal Children’s Hospital, Montreal, QC, Canada,
6
Hematology/Oncology, Hospital Sainte-
Justine, Montreal, QC, Canada,
7
Pediatric Hematology/Oncology, British Columbia Children’s Hospital, Vancouver, BC, Canada,
8
Hematology/Oncology,
McMaster Children’s Hospital at Hamilton Health Sciences, Hamilton, ON, Canada,
9
Pediatrics, IWK Health Centre, Halifax, NS, Canada,
10
Hematology/
Oncology, Cancer Centre of Southeastern Ontario at Kingston, Kingston, ON, Canada,
11
Hematology/Oncology, London Health Sciences, London, ON,
Canada,
12
Pediatric Hematology/Oncology Centre, Hospitalier Universitaire de Quebec, Quebec City, QC, Canada,
13
Hematology/Oncology, Janeway Child
Health Center, St John’s, NL, Canada,
14
Stollery Children’s Hospital, University of Alberta Hospital, Edmonton, AB, Canada,
15
Hematology/Oncology,
Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada,
16
Population Genomics Program, Department of Clinical Epidemiology and
Biostatistics, McMaster University, Hamilton, ON, Canada and
17
Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada
Summary Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in pae-
diatric acute myeloid leukaemia (AML). This study describes risk factors for IFI and
IFI-related sepsis in this population. We conducted a population-based, retrospective
cohort study of children with AML in Canada. IFIs during chemotherapy and prior
to haematopoietic stem cell transplantation, relapse, persistent disease or death were
identified. Risk factors for proven or probable IFI were examined. Among courses
complicated by IFI, risk factors for sepsis were also evaluated. There were 341 chil-
dren with AML included of which 41 (12.0%) experienced 46 different episodes of
IFI. Candida species accounted for 23 (50.0%) of IFIs and Aspergillus spp. accounted
for 14 (30.4%). Days of broad-spectrum antibiotics, days of corticosteroids and neu-
tropenia at start of the course were independently associated with IFI. Only days of
fever were independently associated with IFI-related sepsis. Invasive fungal infections
occurred in 12.0% of paediatric AML patients. Risk factors for IFI and IFI-related
sepsis were identified. This knowledge may help to consider targeted strategies.
Key words: Fungal infection, paediatric acute myeloid leukaemia, risk factors.
Introduction
Infections are major causes of morbidity and mortality
in paediatric acute myeloid leukaemia (AML) related
to the intensity of treatment and its associated pro-
longed and profound neutropenia. Invasive fungal
infections (IFIs) are important because they are
associated with relatively poor outcomes. Previous
studies have demonstrated a cumulative incidence of
IFIs in paediatric AML patients undergoing therapy of
5–13% and have found IFIs to be an attributable
cause of death in 5–18% of patients.
1–6
Published risk
factors for the development of IFIs in paediatric AML
patients include long-term administration of broad-
spectrum antibiotics, relapse therapy, duration of
neutropenia, use of corticosteroid medication and
intensive chemotherapy.
1–3,5
The limitations of previous AML studies include fail-
ure to use standard classification of IFI according to
the European Organization for Research and Treat-
ment in Cancer/Mycoses Study Group (EORTC/MSG),
7
patient population consisting only of those enrolled on
Correspondence: D. Johnston, Children’s Hospital of Eastern Ontario, 401
Smyth Road, Ottawa, ON K1H 8L1, Canada.
Tel.: +(613) 737 7600; ext. 2210. Fax: +(613) 738 4828.
E-mail: djohnston@cheo.on.ca
Submitted for publication 7 December 2012
Revised 23 January 2013
Accepted for publication 30 January 2013
© 2013 Blackwell Verlag GmbH doi:10.1111/myc.12063
mycoses
Diagnosis,Therapy and Prophylaxis of Fungal Diseases