Objectives: There is a lack of guidance on the management of febrile neutropenia in otherwise healthy children, including the need for hospitalization and antibiotic administration, leading to significant practice variation in management. The aim of this initiative was to decrease the number of unnecessary hospitalizations and empirical antibiotics prescribed by 50% over a 24-month period for well-appearing, previously healthy patients older than 6 months presenting to the emergency department with a first episode of febrile neutropenia.
Methods: A multidisciplinary team of stakeholders was assembled to develop a multipronged intervention strategy using the Model for Improvement.
Objective: To assess the cost-effectiveness of an evidence-informed institutional protocol for physicians that encouraged management of children with newly diagnosed immune thrombocytopenia (ITP) with observation over active therapy, where appropriate.
Study Design: We conducted a probabilistic cost-effectiveness analysis from an institutional perspective using a decision tree with a 1 year time horizon. Patient-level data were retrospectively ascertained for children diagnosed in pre-protocol (2007-2009) and post-protocol (2013-2018) time periods.
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%).
View Article and Find Full Text PDFClassification of inherited bone marrow failure syndromes (IBMFSs) according to clinical and genetic diagnoses enables proper adjustment of treatment. Unfortunately, 30% of patients enrolled in the Canadian Inherited Marrow Failure Registry (CIMFR) with features suggesting hereditability could not be classified with a specific syndromic diagnosis. We analyzed the outcome of hematopoietic stem cell transplantation (HSCT) in unclassified IBMFSs (uIBMFSs) and the factors associated with outcome.
View Article and Find Full Text PDFChildren with cancer experience suffering, particularly at the end of life. Pediatric hematology/oncology (PHO) fellows need dedicated palliative care (PC) training in order to adequately manage this suffering. Our objectives were to understand (1) the PC training needs of Canadian PHO fellows and (2) experiences in providing PC, from the perspectives of fellows and their training program directors (PDs) and to describe (1) our experience in enhancing our institutional PC curriculum and (2) the preliminary evaluation of this curriculum.
View Article and Find Full Text PDFVenous thromboembolism (VTE) is now increasingly recognized within paediatrics. A Canadian VTE registry has estimated the incidence as 0.7 to 1.
View Article and Find Full Text PDFPrimary immunodeficiency disorders represent a heterogeneous spectrum of diseases, predisposing to recurrent infections, allergy, and autoimmunity. While an association between primary immunodeficiency disorders and increased risk of cancer has been suggested since the 1970s, renewed attention has been given to this topic in the last decade, largely in light of the availability of large registries as well as advances in next generation sequencing. In this narrative review, we will give an insight of the primary immunodeficiencies that are commonly responsible for the greater number of cancers in the primary immunodeficiency disorders population.
View Article and Find Full Text PDFThe distinction between myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) often relies on an arbitrary marrow blast cutoff of 30% in pediatrics and 20% in adults. There is little data about the treatment of children with extramedullary myeloid malignancy that has features of both, MDS and AML. Herein, we report for the first time 2 patients MDS/AML (1 with Shwachman-Diamond syndrome and 1 with idiopathic MDS and monosomy 7) who presented with extramedullary complications, received treatment with azacitidine, achieved complete remission and subsequently underwent hematopoietic stem cell transplantation.
View Article and Find Full Text PDFProgressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.
View Article and Find Full Text PDFInherited bone marrow failure syndromes (IBMFSs) are genetically heterogeneous disorders with cytopenia. Many IBMFSs also feature physical malformations and an increased risk of cancer. Point mutations can be identified in about half of patients.
View Article and Find Full Text PDFKaposiform hemangioendothelioma (KHE) is a rare infiltrative vascular tumor that may be associated with Kasabach-Merritt Phenomenon (KMP), which is a consumptive coagulopathy with potentially life-threatening thrombocytopenia. Management of KHE and KMP is challenging, and currently, there are no standardized validated treatment protocols. Mammalian target of rapamycin inhibitors have been shown to be effective in the treatment of KHE.
View Article and Find Full Text PDFIVIG has been the predominant therapy for the initial management of children with newly diagnosed immune thrombocytopenia at our hospital. With current guidelines supporting more conservative management, we undertook a quality improvement initiative to lead practice change. Over a 2-year time period (2013 to 2015), we strove to decrease use of hospital resources (use of IVIG, length of stay) while optimizing family satisfaction.
View Article and Find Full Text PDFBackground: ERCC6L2-associated disorder has recently been described and only five patients were reported so far. The described phenotype included bone marrow, cerebral, and craniofacial abnormalities. The aim of this study was to further define the genetic and phenotypic spectrum of the disorder by summarizing the five published cases and an additional case that we identified through whole-exome sequencing performed at the University of Toronto.
View Article and Find Full Text PDFInherited bone marrow failure syndromes (IBMFSs) comprise a genetically heterogeneous group of diseases with hematopoietic failure and a wide array of physical malformations. Copy number variants (CNVs) were reported in some IBMFSs. It is unclear what impact CNVs play in patients evaluated for a suspected diagnosis of IBMFS.
View Article and Find Full Text PDFAdvanced myelodysplastic syndrome harbors a high risk of progression to acute myeloid leukemia and poor prognosis. In children, there is no established treatment to prevent or delay progression to leukemia prior to hematopoietic stem cell transplantation. Azacitidine is a hypomethylating agent, which was shown to slow progression to leukemia in adults with myelodysplastic syndrome.
View Article and Find Full Text PDFPurpose: The purpose of this study was to define the hematologic response to total splenectomy (TS) or partial splenectomy (PS) in children with hereditary spherocytosis (HS) or sickle cell disease (SCD).
Methods: The Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium registry collected hematologic outcomes of children with CHA undergoing TS or PS to 1 year after surgery. Using random effects mixed modeling, we evaluated the association of operative type with change in hemoglobin, reticulocyte counts, and bilirubin.
Background: Phenotypic overlap among the inherited bone marrow failure syndromes (IBMFSs) frequently limits the ability to establish a diagnosis based solely on clinical features. >70 IBMFS genes have been identified, which often renders genetic testing prolonged and costly. Since correct diagnosis, treatment and cancer surveillance often depend on identifying the mutated gene, strategies that enable timely genotyping are essential.
View Article and Find Full Text PDFInherited 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.
View Article and Find Full Text PDFThe outcomes of children with congenital hemolytic anemia (CHA) undergoing total splenectomy (TS) or partial splenectomy (PS) remain unclear. In this study, we collected data from 100 children with CHA who underwent TS or PS from 2005 to 2013 at 16 sites in the Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium using a patient registry. We analyzed demographics and baseline clinical status, operative details, and outcomes at 4, 24, and 52 weeks after surgery.
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