Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020-May 2021.

Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada. Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program (CPSP) from April 2020-May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization. Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60·7% with COVID-19-related disease and 39·3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1·9 years (IQR 0·1-13·3) and 43·0% had chronic comorbid conditions. Severe disease occurred in 29·7% of COVID-19-related hospitalizations (n=98/330 including 60 admitted to intensive care), most frequently among children aged 2-4 years (48·7%) and 12-17 years (41·3%). Comorbid conditions associated with severe disease included pre-existing technology dependence requirements (adjusted risk ratio [aRR] 2·01, 95% confidence interval [CI] 1·37-2·95), body mass index Z-scores ≥3 (aRR 1·90, 95% CI 1·10-3·28), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1·84, 95% CI 1·32-2·57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1·63, 95% CI 1·12-2·39). Interpretation: While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children. Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.

Defining vascular anomaly phenotypes in children based on a systematic literature search: A critical step in developing a single severity score for interventional clinical trials.

INTRODUCTION: Genetically targeted drugs in vascular anomalies (VA) are used despite the absence of a validated severity score. The aim of this study was to evaluate the feasibility of grouping phenotypic VA clinical characteristics into a single severity score. METHODS: A systematic literature review including children treated with sirolimus accompanied by a detailed description of phenotype and management was conducted. Demographic data and clinical features were extracted to define distinct categories of phenotypes. RESULTS: Children with VA display two main phenotypes regardless of VA subtype, which may overlap. A systemic phenotype results from direct invasion and compression of vital structures generally leading to hospitalization and aggressive management in infancy. A functional phenotype is associated with chronic pain and disability manifesting mainly during early adolescence and managed in the outpatient setting. CONCLUSION: The two distinct phenotypes described could be the basis for developing a unified scoring system for VA severity assessment.

Pediatric Benign Neutropenia: Assessing Practice Preferences in Canada.

Pediatric benign neutropenia is a self-limited condition with a benign clinical course. An approach to this condition is not well-defined in the literature. Our objective was to use a case-based survey to elucidate trends in the diagnosis and management of benign neutropenia among pediatric hematology/oncology practitioners in Canada. We received 46 completed surveys (response rate 66%). At initial presentation with fever and neutropenia, 67% of respondents recommended partial septic workup but 11% recommended no investigations. Nearly 70% recommended admission for empiric intravenous antibiotics, while 24% would discharge home without antibiotics. In a patient with fever and known neutropenia, respondents were more likely to pursue outpatient antibiotic therapy. For investigation of chronic neutropenia, most respondents (60%) do not use antineutrophil antibody testing. Common indications for bone marrow biopsy were severe infection, prolonged neutropenia, or before initiating granulocyte colony stimulating factor. Indications for granulocyte colony stimulating factor were based on severity and frequency of infection. Most respondents (84%) would not recommend antibiotic prophylaxis. Results demonstrate the considerable variability in management of benign neutropenia among pediatric hematology/oncology practitioners in Canada and highlight the need for prospective studies to establish diagnostic criteria for benign neutropenia and evaluate management of fever in this population.

Optimizing pharmacologic thromboprophylaxis use in pediatric orthopedic surgical patients through implementation of a perioperative venous thromboembolism risk screening tool.

BACKGROUND: Although rare, venous thromboembolic events (VTE) are a significant challenge in pediatric orthopedic surgical patients (POSP). A VTE thromboprophylaxis screening tool was developed and implemented in POSPs at the IWK Health Centre since October 2016. OBJECTIVES: This retrospective cohort study was designed to evaluate and assess the impact of the VTE thromboprophylaxis screening tool in terms of use of thromboprophylaxis in POSP. METHODS: Using the tool, POSPs were screened and were categorized into risk groups. Patient groups were compared and spearman correlation analysis was performed to show the strength of association between risk factors and thromboprophylaxis. Retrospective screening of pre-algorithm patients who received thromboprophylaxis was done to further assess the screening tool. RESULTS: After the implementation of the VTE thromboprophylaxis screening tool in POSPs, there was a 47.9% reduction in the use of thromboprophylaxis (P = 0.046) as compared with before. Neither VTE nor significant bleeding complications occurred before or after screening tool implementation. Compliance with the screening tool was excellent (100% of patients in the high-risk category received thromboprophylaxis). High-risk patients were more likely to have body mass index  > 30 (35.7%), limited/altered mobility (57.1%), and to be undergoing a complicated/repeat surgery (64.3%). CONCLUSIONS: The present study demonstrates successful implementation of a VTE thromboprophylaxis screening tool that resulted in significant reduction in use of thromboprophylaxis in POSPs with no increase in VTE or change in bleeding complications.

Improving Time to Antibiotics for Pediatric Oncology Patients With Fever and Suspected Neutropenia by Applying Lean Principles.

BACKGROUND: Fever in the setting of neutropenia is a potentially life-threatening complication of cancer treatment. A time of less than 60 minutes from presentation to antibiotic administration is therefore recommended. OBJECTIVE: To use Lean Six Sigma methodology, a quality improvement initiative, to improve time to antibiotics (TTA) for children with chemotherapy-induced febrile neutropenia presenting to the emergency department. METHODS: Lean Six Sigma is a quality improvement method that engages all impacted stakeholders and focuses on streamlining the process by removing process wastes. Stakeholders identified multiple process wastes in an in-depth study of 49 fever episodes in patients attending a tertiary care pediatric hospital, including patients waiting to be registered, waiting for laboratory technicians, delay in accessing central venous access device, waiting for absolute neutrophil count, and delayed antibiotics orders. We implemented multiple solutions: engaging patients in the process through predischarge tours of the emergency department, home application of topical anesthetic, nurse-initiated pathway, early access of central venous access device for all blood work, and planned antibiotic administration no later than 45 minutes after triage. We prospectively determined the impact of these interventions on TTA. RESULTS: The TTA significantly improved to a median of 59 minutes (interquartile range, 38.5-77.5 minutes) compared with the baseline of 99 minutes (interquartile range, 72.0-132.0 minutes; P < 0.0001). CONCLUSIONS: Lean methodology effectively identifies barriers and provides solutions to remove barriers and improve administration of antibiotics in febrile oncology patients. These can be widely applied, including in smaller institutions with minimal increased utilization of resources.

Waning Vaccine Immunity and Vaccination Responses in Children Treated for Acute Lymphoblastic Leukemia: A Canadian Immunization Research Network Study.

BACKGROUND: There is no uniform guideline for postchemotherapy vaccination of children with acute lymphoblastic leukemia (ALL). We evaluated waning immunity to 14 pneumococcal serotypes, pertussis toxin (PT), tetanus toxoid (TT) and varicella, and immunogenicity of postchemotherapy diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) and pneumococcal vaccination among previously vaccinated children treated for ALL. METHODS: This was a multicenter trial of children with ALL enrolled 4-12 months postchemotherapy completion. Exclusion criteria included: infant ALL, relapsed ALL, and stem cell transplant recipients. Immunocompetent children were recruited as controls. Postchemotherapy participants received DTaP-IPV-Hib and 13-valent pneumococcal conjugate vaccine (PCV13) concurrently, followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later. Serology was measured at baseline, 2 and 12 months postvaccination. Adverse events were captured via surveys. RESULTS: At enrollment, postchemotherapy participants (n = 74) were less likely than controls (n = 78) to be age-appropriately immunized with DTaP (41% vs 89%, P < .001) and PCV (59% vs 79%, P = .008). Geometric mean concentrations (GMCs) to TT, PT, PCV serotypes, and varicella were lower in postchemotherapy participants than controls after adjusting for previous vaccine doses (P < .001). Two months postvaccination, GMCs to TT, PT, and PCV serotypes increased from baseline (P < .001 for all antigens) and remained elevated at 12 months postvaccination. Antibody levels to PPV23 serotypes also increased postvaccination (P < .001). No serious adverse events were reported. CONCLUSIONS: Children treated for ALL had lower antibody levels than controls against pneumococcal serotypes, tetanus, pertussis, and varicella despite previous vaccination. Postchemotherapy vaccination with DTaP-IPV-Hib, PCV13, and PPV23 was immunogenic and well tolerated. Children with ALL would benefit from systematic revaccination postchemotherapy. CLINICAL TRIALS REGISTRATION: NCT02447718.

Development of a perioperative venous thromboembolism prophylaxis algorithm for pediatric orthopedic surgical patients.

Venous thromboembolism (VTE) has been recognized as a rare but potentially serious complication in pediatric orthopedic patients. However, standardized guidelines for screening and management of at-risk patients do not exist. The aim of the study was to develop a VTE prophylaxis screening tool for postoperative orthopedic patients after conducting an institutional needs assessment survey. A needs assessment survey was conducted after institutional ethics board approval. Development of perioperative VTE prophylaxis algorithm for pediatric orthopedic surgical patients was planned after thorough literature review, consultation with national and international experts as well as using a modified nominal and consensus development conference (serial meetings) method for reaching a consensus. NAS as well as discussion with stakeholders indicated support for development of perioperative VTE prophylaxis algorithm for orthopedic patients. Using above methods, a VTE prophylaxis algorithm was developed and implemented at IWK Health Center. The present study involved development of a perioperative VTE prophylaxis algorithm for pediatric orthopedic surgical patients that could be easily and rapidly administered as a point of care assessment tool.

Abnormal hemostasis in children with vascular anomalies, part I: Thrombocytopenias among different vascular anomalies.

Long before the classification of vascular anomalies from the International Society for the Study of Vascular Anomalies (ISSVA) provided a framework to differentiate vascular anomalies, otherwise known as vascular birthmarks, it was recognized that patients with such lesions can present with acute life-threatening hemostatic and/or thrombotic complications, as well as chronic long-standing bleeding or thrombotic issues. Scenarios such as a rapidly growing vascular lesion with severe acute thrombocytopenia, a visceral hemorrhagic lesion, a lesion associated with repetitive and painful superficial thrombosis, and cases of unprovoked or post-procedural fatal pulmonary embolism highlight the wide spectrum of manifestations of abnormal coagulation in patients with vascular anomalies. The separation of vascular anomalies into two distinct groups, vascular tumors and vascular malformations, was followed by the characterization that their respective coagulopathies were due to either a derangement of platelets or to a disequilibrium of the patient's coagulation/fibrinolytic process. This configuration of coagulopathies will be the foundation for this two-chapter review series. In the initial review, coagulopathies where thrombocytopenia is the main feature will be characterized, whereas the second review will focus on vascular malformations that have a coagulation disorder secondary to some degree of coagulation consumption and/or fibrinolytic pathway derangement.

Cancer Risk in Klippel-Trenaunay Syndrome.

Background: Klippel-Trenaunay syndrome (KTS) is an overgrowth syndrome defined by capillary/venous/lymphatic malformations (CVLM) with soft tissue and/or bone hypertrophy. Whether KTS predisposes to cancer is not clear. Methods and Results: We surveyed members of the K-T Support Group (KTSG) and reviewed PubMed for "Klippel Trenaunay Syndrome" or "CVLM" and "cancer." Individuals with cancer were reviewed for confirmation of KTS, tumor type, location, and age at presentation. Of 223 KTSG respondents, 24 (10.8%) reported 26 malignancies or benign brain tumors (diagnosed from 6 months to 68 years of age, median 41 years), including 3 who were younger than 18 years (2 with Wilms tumor). Nine of twenty-six cancers were basal cell carcinomas (4% of respondents). From 475 articles, we identified 11 cancers or brain tumors in 10 individuals with KTS. Four of these were in children (Wilms tumor n = 2; rhabdomyosarcoma n = 1; serous borderline tumor n = 1). Tumors in adults included basal cell carcinoma (n = 1), squamous cell carcinoma of skin (n = 2), and angiosarcoma, Hodgkin disease, glioblastoma, malignant hemangiopericytoma in one patient each. Ulceration or lymphedema associated with VLM or capillary malformations were associated with some basal cell or squamous cell carcinomas and angiosarcomas. Conclusions: The risk of embryonal cancer other than Wilms tumor in children with KTS does not appear to be higher than in the general population. Wilms tumor incidence is under 5%, and routine surveillance is not indicated. In adults, particular attention should be paid to skin in the area of malformations. These conclusions may not apply to all overgrowth syndromes with vascular malformations.

Severely bothersome fatigue in children and adolescents with cancer and hematopoietic stem cell transplant recipients.

BACKGROUND: Objectives were to describe bothersome fatigue in children with cancer and hematopoietic stem cell (HSCT) recipients and to identify factors associated with severely bothersome fatigue. METHODS: We included children ages 8-18 years treated for cancer or HSCT recipients from three groups: [1] receiving active cancer treatment and admitted to hospital for at least 3 days, [2] attending outpatient clinic for acute lymphoblastic leukemia maintenance therapy, and [3] attending outpatient clinic following treatment completion. Fatigue was measured using the Symptom Screening in Pediatrics Tool (SSPedi); severely bothersome fatigue was defined as a lot or extremely bothersome fatigue (score of 3-4 on 0-4 scale). Factors associated with severely bothersome fatigue were examined using univariate and multiple logistic regression. RESULTS: Of 502 children included, 414 (82.5%) reported some degree of bothersome fatigue (scores 1-4), and 123 (24.5%) reported severely bothersome fatigue (score 3 or 4). In multiple regression analysis, factors significantly associated with severely bothersome fatigue were child age 11-14 and 15-18 years vs 8-10 years (odds ratio (OR) 2.11, 95% confidence interval (CI) 1.21-3.77 and OR 2.96, 95% CI 1.66-5.44), and inpatients receiving cancer treatment vs outpatients who had completed therapy (OR 3.85, 95% CI 2.17-7.27). CONCLUSIONS: We found that 82.5% of children with cancer or HSCT recipients reported bothersome fatigue and 24.5% of children reported severely bothersome fatigue. Risk factors for severely bothersome fatigue were older age and inpatients receiving active cancer treatment. Future work should evaluate systematic symptom screening in clinical practice and apply interventions to reduce fatigue.

Perianal Infections in Children With Acute Myeloid Leukemia: A Report From the Canadian Infection in Acute Myeloid Leukemia Research Group.

Among 235 children with acute myeloid leukemia, 17 experienced 19 perianal infections. Among 12 episodes with definite abscess, 75% were severely neutropenic. Sixteen diagnostic imaging evaluations were performed; diagnostic yield was similar between computerized tomography of pelvis (5 of 10) and ultrasound (3 of 5). Consistent management approaches to perianal infection should be developed.

Taste changes in children with cancer and hematopoietic stem cell transplant recipients.

BACKGROUND: Objectives were to describe bothersome self-reported changes in taste in pediatric oncology and hematopoietic stem cell (HSCT) patients and to identify patient and treatment-related factors associated with bothersome taste changes. METHODS: We prospectively enrolled children and adolescents with cancer or pediatric HSCT recipients 8-18 years of age from three groups: inpatients receiving cancer treatments; outpatients in maintenance therapy for acute lymphoblastic leukemia (ALL); and outpatients in survivorship. Bothersome changes in taste was self-reported using the Symptom Screening in Pediatrics Tool (SSPedi); nausea was self-reported using the Pediatric Nausea Assessment Tool (PeNAT). RESULTS: Among the 502 children included, 226 (45.0%) reported bothersome taste changes and 48 (9.6%) reported severely bothersome taste changes. In multiple regression, factors independently associated with severely bothersome taste changes were: inpatients receiving cancer treatments vs outpatients in survivorship (odds ratio (OR) 12.28, 95% confidence interval (CI) 2.50-222.27), ALL in maintenance vs outpatients in survivorship (OR 7.43, 95% CI 1.06-147.77), current nausea (OR 1.59, 95% CI 1.04-2.42), vomiting (OR 2.18, 95% CI 1.06-4.38), and first language not English (OR 2.09, 95% CI 0.97-4.28). CONCLUSIONS: We found that 45% of children with cancer and pediatric HSCT recipients reported bothersome changes in taste and these were severely bothersome in 9.6% of children. Inpatients receiving cancer treatment, those experiencing more nausea and vomiting and children whose first language was not English were at greater risk of severely bothersome changes in taste. Future work should evaluate systematic symptom screening in clinical practice and identify interventions focused on addressing bothersome taste changes.

Adenovirus Infection in Children With Acute Myeloid Leukemia: A Report From the Canadian Infection in Acute Myeloid Leukemia Research Group.

BACKGROUND: Children with acute myeloid leukemia (AML) are at high risk of life-threatening bacterial and fungal infection. However, little is known about the prevalence or severity of adenovirus infection in this population. Objective was to describe the characteristics, treatments and outcomes of adenovirus infection in children with newly diagnosed AML. METHODS: We performed a retrospective chart review based upon 2 multicenter cohort studies that focused on identifying risk factors for infection in children with AML. Inclusion criteria were patients with de novo AML who were ≤18 years of age at diagnosis with a clinical specimen positive for adenovirus. RESULTS: Among the 235 patients with AML, 12 (5.1%) had positive adenovirus testing. The most common site of isolation was stool (n = 11, 91.6 %), and the most frequent symptom was diarrhea (n = 11, 91.6 %). Two patients received specific treatment for adenovirus, namely intravenous immunoglobulin only in 1 patient and both intravenous immunoglobulin and inhaled ribavirin in a second patient. In 11 patients, adenovirus resolved uneventfully without recurrence, including 10 that received no adenovirus-specific therapy. However, 1 patient developed sepsis syndrome in the setting of disseminated adenoviral infection and died from multiorgan failure. CONCLUSION: In children with AML, adenovirus infection was rare and typically not associated with severe disease, even without specific treatment. However, disseminated and fatal disease can occur in this population. Further investigations are needed to identify pediatric AML patients at particular risk for severe adenovirus infection and to determine optimal treatment approaches in these patients.

Invasive Rothia infections in children with acute myeloid leukemia: A report from the Canadian infections in AML research group.

Rothia spp. (previously termed Stomatococcus) are normal flora that can cause invasive infections in immunocompromised hosts. The objective of this study was to describe infection characteristics and outcomes of Rothia spp. infections in a large cohort of children with newly diagnosed acute myeloid leukemia (AML). This retrospective chart review is a subanalysis of a larger study in which the aim was to identify factors associated with infection in pediatric patients with AML. Only sterile site infections occurring during chemotherapy were included. Among 578 children with AML, 17 (2.9%) children with at least 1 Rothia spp. infection were identified. All children were neutropenic at the time of infection. Eight (47%) had antecedent colitis or mucositis. Of the 17 infections, 16 were bacteremia and 1 was meningitis. Sepsis occurred in 4 patients, and 1 patient died due to infection. Rothia spp. infections are rare in pediatric AML but can cause significant morbidity and mortality. Future studies should describe trends in incidence and resistance patterns over time.

Fluoxetine-Induced Hypoglycaemia in a Patient with Congenital Hyperinsulinism on Lanreotide Therapy.

Antidepressant drugs are reported to cause alterations in blood glucose homeostasis in adults with diabetes mellitus. We report a patient with persistent congenital hyperinsulinism (CHI) who developed recurrent hypoglycaemia following fluoxetine therapy. This 15-year-old girl was initially managed with diazoxide therapy. She developed troublesome hypertrichosis, which affected her quality of life adversely. Diazoxide was then slowly weaned and stopped with the introduction of octreotide, to which she responded well. Subcutaneous lanreotide (long-acting somatostatin analogue) was subsequently commenced (30 mg, once monthly) as injecting octreotide multiple times a day was proving to be difficult for the patient. The continuous blood glucose monitoring on monthly lanreotide injections revealed good glycaemic control. Six months later, she developed depression due to psychosocial problems at school. She was started on fluoxetine by the psychiatry team. She subsequently developed recurrent symptomatic hypoglycaemic episodes (blood glucose <3.5 mmol/L) and fluoxetine was discontinued, following which the hypoglycaemic episodes resolved within a week. Fluoxetine has been associated with hypoglycaemia in patients with diabetes mellitus. We report, for the first time, hypoglycaemia secondary to fluoxetine in a patient with CHI.

Study of Glycine and Folic Acid Supplementation to Ameliorate Transfusion Dependence in Congenital SLC25A38 Mutated Sideroblastic Anemia.

Congenital sideroblastic anemia (CSA) is a hematological disorder characterized by the presence of ringed sideroblasts in bone marrow erythroid precursors. Mutations in the erythroid-specific glycine mitochondrial transporter gene SLC25A38 have been found in a subset of patients with transfusion-dependent congenital CSA. Further studies in a zebrafish model identified a promising ameliorative strategy with combined supplementation with glycine and folate. We tested this combination in three individuals with SLC25A38 CSA, with a primary objective to decrease red blood cell transfusion requirements. No significant impact was observed on transfusion requirements or any hematologic parameters.

Immunization practices in acute lymphocytic leukemia and post-hematopoietic stem cell transplant in Canadian Pediatric Hematology/Oncology centers.

There are no Canadian immunization guidelines for children treated for malignancy. Guidelines do exist for patients who underwent hematopoietic stem cell transplant (HSCT), but they provide broad timeframes for initiating vaccination; there is no standard schedule. The optimal approach to immunization in these populations is unclear. We sought to describe immunization practices at Canadian Pediatric Hematology/Oncology centers. A 43-item online questionnaire was distributed to the 16 programs in the C(17) research network of pediatric hematology/oncology centers to capture information on timing and criteria for immunization of patients with acute lymphocytic leukemia (ALL) and those who have undergone HSCT. At each center, 1-2 physicians or pharmacists completed the survey to reflect center-wide immunization practices. Responses were received from 11/16 (69%) programs; 11 respondents reported on practices for patients with ALL and 9 reported on practices for patients who are post-HSCT. In 5/11 ALL programs (45%) re-immunization is recommended routinely after chemotherapy, starting 3-6 months post-chemotherapy. In HSCT programs, timing of pneumococcal conjugate vaccination (PCV) varied from 3 months post-HSCT (4 programs) to 12 months post-HSCT (4 programs). Live vaccines were administered 24 months post-HSCT in 8/9 programs. All HSCT programs considered graft-versus-host-disease and 7 considered discontinuation of immunosuppression in immunization decisions. Pediatric hematology/oncology programs were divided in regards to re-immunization of patients with ALL post-chemotherapy. After HSCT, timing of PCV administration varied, with 4 programs initiating immunization later than Canadian guidelines recommend (3-9 months post-HSCT). These findings suggest a need to standardize immunization practices in these populations.

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

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.

Combined Autoimmune Cytopenias Presenting in Childhood.

BACKGROUND: Pediatric patients with chronic and/or refractory autoimmune multi-lineage cytopenias present challenges in both diagnosis and management. Increasing availability of diagnostic testing has revealed an underlying immune dysfunction in patients previously diagnosed with Evans Syndrome. However, the data are sparse and the majority of patients are adults. PROCEDURE: We performed a retrospective chart review to document the natural history of 23 pediatric patients with autoimmune multi-lineage cytopenias followed at three tertiary care pediatric hematology clinics. RESULTS: Investigations revealed seven patients (30.4%) with an autoimmune lymphoproliferative-like syndrome and six patients (26.1%) with other primary immunodeficiencies. Only one (4.3%) patient was suspected to have systemic lupus erythematosus and six patients (26.1%) had other types of autoimmunity. Treatment consisted of immunosuppressive therapy, intravenous gammaglobulin, and splenectomy. Supportive care included granulocyte-colony stimulating factor, and blood product transfusions. Two patients (8.7%) died. Complete remission was achieved in 3 patients (13.0%); of the remaining, 14 patients (60.9%) had chronic immune thrombocytopenic purpura, 10 patients (43.5%) chronic autoimmune neutropenia, and 4 patients (17.4%) chronic autoimmune hemolytic anemia with a median follow up of 5 years (2 months-12 years). CONCLUSIONS: These data suggest that pediatric patients presenting with autoimmune multi-lineage cytopenias should undergo investigation for underlying immune dysregulation, including autoimmune lymphoproliferative syndrome, other primary immunodeficiencies and autoimmune disorders. The development of an international registry for such patients is imperative to improve the understanding of their complex natural history.

Predictors and outcomes of viridans group streptococcal infections in pediatric acute myeloid leukemia: from the Canadian infections in AML research group.

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/m² (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.