Janeway Child Health Center

St. John's, Canada

Janeway Child Health Center

St. John's, Canada

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Lewis V.,Alberta Childrens Hospital | Yanofsky R.,Hematology Oncology | Mitchell D.,Montreal Childrens Hospital | Dix D.,British Columbia Childrens Hospital | And 13 more authors.
Pediatric Infectious Disease Journal | Year: 2014

BACKGROUND:: Viridans group streptococci (VGS) cause significant morbidity in children treated for acute myeloid leukemia (AML). Our goals were to determine the occurrence and impact of these infections in children treated for AML and to understand the factors that increase the risk of VGS infections and viridans streptococcal shock syndrome (VSSS) in this population. METHODS:: We conducted a retrospective, population-based cohort study that included children ≤18 years of age with de novo AML treated at 15 Canadian centers. We evaluated factors related to VGS infection and VSSS. RESULTS:: Among 341 children with AML, VGS occurred in 78 (22.9%) children over the entire course of therapy and 16 had recurrent episodes. VGS infection occurred in 97 of 1277 courses of chemotherapy (7.6%). VSSS occurred in 19.6% of these episodes and included 11 patients who required intensive care services with 2 VGS infections resulting in death. In multiple regression analysis, factors independently related to VGS included treatment on a Medical Research Council-based protocol (odds ratio (OR) 2.87, 95% confidence interval (CI) 1.53-5.39; P = 0.001), cytarabine dose per gram/m (OR 1.04, 95% CI 1.01-1.07; P = 0.002) and prolonged neutropenia (OR 1.58, 95% CI: 0.97-2.56; P = 0.06). None of the evaluated factors were predictive of VSSS. CONCLUSIONS:: VGS infections occur in 7.6% of chemotherapy courses and remain an important cause of morbidity and even mortality in children being treated for AML. Interventions to reduce VGS need to be identified. Copyright © 2013 by Lippincott Williams & Wilkins.


Johnston D.L.,Childrens Hospital of Eastern Ontario | Lewis V.,Alberta Childrens Hospital | Yanofsky R.,Hematology Oncology | Gillmeister B.,The Hospital for Sick Children | And 14 more authors.
Mycoses | Year: 2013

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in paediatric 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 children 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 neutropenia 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. © 2013 Blackwell Verlag GmbH.


Price V.,Health Center | Portwine C.,Hamilton Health Sciences | Zelcer S.,Hematology Oncology | Ethier M.-C.,Hospital for Sick Children | And 16 more authors.
Pediatric Infectious Disease Journal | Year: 2013

Background: The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI. Method: We performed a multicenter, retrospective cohort study of children with de novo AML and evaluated CDI. Recurrence, sepsis and infection-related death were examined. Factors associated with CDI were also evaluated. Results: Forty-three CDI occurred in 37 of 341 (10.9%) patients during 42 of 1277 (3.3%) courses of chemotherapy. There were 6 children with multiple episodes of CDI. Three infections were associated with sepsis, and no children died of CDI. Only 2 children had an associated enterocolitis. Both days of broad-spectrum antibiotics (odds ratio 1.03, 95% confidence interval: 1.01 to 1.06; P = 0.003) and at least 1 microbiologically documented sterile site infection (odds ratio 10.81, 95% confidence interval: 5.88 to 19.89; P < 0.0001) were independently associated with CDI. Conclusions: CDI occurred in 11% of children receiving intensive chemotherapy for AML, and outcomes were not severe. CDI is not a prominent issue in pediatric AML in terms of prevalence, incidence or associated outcomes. Copyright © 2013 by Lippincott Williams & Wilkins.


PubMed | The Hospital for Sick Children, London Health Sciences Center, Alberta Childrens Hospital, McMaster University and 10 more.
Type: Journal Article | Journal: Journal of the Pediatric Infectious Diseases Society | Year: 2015

The risk of second bacteremia during antibiotic treatment for initial bacteremia is unknown in high-risk populations. Our objectives were to describe the prevalence of second bacteremia during treatment and identify risk factors in children with acute myeloid leukemia (AML).We conducted a retrospective, population-based cohort study that included children and adolescents with de novo, non-M3 AML who were diagnosed and treated between January 1, 1995 and December 31, 2004 at 15 Canadian centers. Patients were monitored for bacteremia during chemotherapy until completion of treatment, hematopoietic stem cell transplantation, relapse, refractory disease, or death.There were 290 episodes of bacteremia occurring in 185 (54.3%) of 341 children. Eighteen (6.2%) had a second bacteremia while receiving antibiotic treatment. Two episodes of second bacteremia were complicated by sepsis; there were no infection-related deaths. Eleven episodes (61.1%) had either an initial Gram-positive and subsequent Gram-negative bacteremia or initial Gram-negative followed by Gram-positive bacteremia. Days receiving corticosteroids (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.07-1.12; P < .0001), cumulative dose of corticosteroids (OR, 1.04; 95% CI, 1.00-1.08; P = .035), and days of neutropenia from start of course to initial bacteremia (OR, 1.07; 95% CI, 1.02-1.12; P = .007) were significantly associated with second bacteremia.In pediatric AML, 6% of patients will experience a second bacteremia during antibiotic treatment; duration of corticosteroid exposure and neutropenia are risk factors. These patients remain at high risk for second bacteremia after identification of the initial bacteremia and warrant continued broad-spectrum treatment during profound neutropenia.


PubMed | The Hospital for Sick Children, Janeway Child Health Center, Alberta Childrens Hospital, Childrens Hospital Oakland Research Institute and 11 more.
Type: Journal Article | Journal: International journal of cancer | Year: 2016

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged 18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p=0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p=0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML.


PubMed | Alberta Childrens Hospital, Child Health Evaluative science, Janeway Child Health Center, University of Toronto and 13 more.
Type: Journal Article | Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases | Year: 2016

We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged 18years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.


Halton J.M.,University of Ottawa | Hand J.,Janeway Child Health Center | Byron P.,British Columbia Childrens Hospital | Strother D.,University of Calgary | Blanchette V.,University of Toronto
Pediatric Blood and Cancer | Year: 2013

Background: A Human Resources (HR) Committee of C17, the national network of Canadian academic pediatric hematology/oncology programs, obtained comprehensive data enabling analysis and planning for the physician workforce. This study establishes physician to patient ratios and predicts workforce needs for Canadian pediatric hematology/oncology programs. Procedures: Over a 10-year period, six surveys were sent to the 17 pediatric tertiary care centers treating children with cancer and blood disorders. Data were obtained on physician demographics, full time equivalent (FTE) positions, and time spent in clinical, research, education, and administrative activities. Survey results were debated at the C17 national meetings to obtain consensus on workload ratios. Results: Since 1999, the pediatric hematologist/oncologist workforce has increased from 71 FTE (43 oncology, 20 hematology, 8 BMT) to 109.5 FTE positions (69.7 oncology, 29.4 hematology, and 10.4 BMT). The median age of pediatric hematologists/oncologists increased from 46 years to 52 years and the male to female ratio changed from 1.8:1 to 0.9:1. The 2011 job profile showed the median time spent on activities was 60% clinical, 15% education, 15% research, and 10% administration. After assessing workload, models of care, and optimal physician FTE per program, the C17 HR Committee recommended a ratio of one oncologist per 15 newly diagnosed patients with malignancy and a ratio of one BMT physician per 15 transplants. For every 2.5 oncologists, a 1.0 hematologist is the minimum required. Conclusion: Physician staffing ratios for pediatric hematology/oncology programs have been established and should be adopted across Canadian academic institutions as a standard. © 2012 Wiley Periodicals, Inc.


Cada M.,The Hospital for Sick Children and the University of Toronto | Segbefia C.I.,The Hospital for Sick Children and the University of Toronto | Klaassen R.,Childrens Hospital of Eastern Ontario | Fernandez C.V.,Health Center | And 20 more authors.
Haematologica | Year: 2015

Inherited bone marrow failure syndromes are a group of rare, heterogeneous genetic disorders with a risk of clonal and malignant myeloid transformation including clonal marrow cytogenetic abnormalities, myelodysplastic syndrome and acute myeloid leukemia. The clinical characteristics, risk classification, prognostic factors and outcome of clonal and malignant myeloid transformation associated with inherited bone marrow failure syndromes are largely unknown. The aims of this study were to determine the impact of category, cytopathology and cytogenetics, the three components of the “Category Cytology Cytogenetics” classification of pediatric myelodysplastic syndrome, on the outcome of clonal and malignant myeloid transformation associated with inherited bone marrow failure. We used data from the Canadian Inherited Marrow Failure Registry. Among 327 patients with inherited bone marrow failure syndrome enrolled in the registry, the estimated risk of clonal and malignant myeloid transformation by the age of 18 years was 37%. The risk of clonal and malignant myeloid transformation varied according to the type of inherited bone marrow failure syndrome but was highest in Fanconi anemia. The development of clonal and malignant myeloid transformation significantly affected overall survival. Mortality varied based on cytopathological group. The largest group of patients had refractory cytopenia. Clonal marrow cytogenetic abnormalities were identified in 87% of patients with clonal and malignant myeloid transformation, and different cytogenetic groups had different impacts on disease progression. We conclude that category, cytopathology and cytogenetics in cases of clonal and malignant myeloid transformation associated with inherited bone marrow failure syndromes have an important impact on outcome and that the classification of such cases should incorporate these factors. © 2015 Ferrata Storti Foundation.


Hashmi S.K.,University of Toronto | Allen C.,University of Toronto | Klaassen R.,Childrens Hospital of Eastern Ontario | Fernandez C.V.,Isaak Walton Killam Hospital for Children | And 16 more authors.
Clinical Genetics | Year: 2011

Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman-Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population-based study. Thirty-four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS-negative SDS patients may have more severe hematological failure and milder pancreatic disease. © 2010 John Wiley & Sons A/S.


PubMed | Alberta Childrens Hospital, Janeway Child Health Center, CancerCare Manitoba, McMaster University and 14 more.
Type: Journal Article | Journal: Haematologica | Year: 2015

Inherited bone marrow failure syndromes are a group of rare, heterogeneous genetic disorders with a risk of clonal and malignant myeloid transformation including clonal marrow cytogenetic abnormalities, myelodysplastic syndrome and acute myeloid leukemia. The clinical characteristics, risk classification, prognostic factors and outcome of clonal and malignant myeloid transformation associated with inherited bone marrow failure syndromes are largely unknown. The aims of this study were to determine the impact of category, cytopathology and cytogenetics, the three components of the Category Cytology Cytogenetics classification of pediatric myelodysplastic syndrome, on the outcome of clonal and malignant myeloid transformation associated with inherited bone marrow failure. We used data from the Canadian Inherited Marrow Failure Registry. Among 327 patients with inherited bone marrow failure syndrome enrolled in the registry, the estimated risk of clonal and malignant myeloid transformation by the age of 18 years was 37%. The risk of clonal and malignant myeloid transformation varied according to the type of inherited bone marrow failure syndrome but was highest in Fanconi anemia. The development of clonal and malignant myeloid transformation significantly affected overall survival. Mortality varied based on cytopathological group. The largest group of patients had refractory cytopenia. Clonal marrow cytogenetic abnormalities were identified in 87% of patients with clonal and malignant myeloid transformation, and different cytogenetic groups had different impacts on disease progression. We conclude that category, cytopathology and cytogenetics in cases of clonal and malignant myeloid transformation associated with inherited bone marrow failure syndromes have an important impact on outcome and that the classification of such cases should incorporate these factors.

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