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Introduction: From the advancement of treatment of pediatric cancer diagnosis, the five-year survival rate has increased significantly. However, the adverse consequence of improved survival rate is the second malignant neoplasm. Although previous studies provided information on the incidence and risk of SMN in long term survivors of childhood cancer, there is still scarce information known for short term (< 5 years) prognosis. This study aims to assess the incidence, characteristics, management, and outcome of children who develop SMN malignancies within 5 years of diagnosis of their initial cancer. Method: This is a retrospective cohort study of early Second Malignant Neoplasms (SMN) in pediatric oncology patients. The Cancer in Young People - Canada (CYP-C) national pediatric cancer registry was used and reviewed pediatric patients diagnosed with their first cancer from 2000-2015. Results: A total of 20,272 pediatric patients with a diagnosis of a first malignancy were analyzed. Of them, 0.7% were diagnosed with a SMN within the first 5 years following their first cancer diagnosis. Development of a SMN impacted survival, shown by an inferior survival rate in the SMN cohort (79.1%) after three years compared to that of the non-SMN cohort (89.7%). Several possible risk factors have been identified in the study including the use of epipodophyllotoxins, exposure to radiation, and hematopoietic stem cell 169 transplant. Discussion: This is the first national study assessing the incidence, 170 characteristics, risk factors and outcome of early SMN in Canadian children 171 from age 0-15 from 2000-2015. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had a major impact on access to health care resources. Our objective was to estimate the impact of the COVID-19 pandemic on the incidence of childhood cancer in Canada. We also aimed to compare the proportion of patients who enrolled in clinical trials at diagnosis, presented with metastatic disease or had an early death during the first 9 months of the COVID-19 pandemic compared with previous years.Methods: We conducted an observational study that included children younger than 15 years with a new diagnosis of cancer between March 2016 and November 2020 at 1 of 17 Canadian pediatric oncology centres. Our primary outcome was the monthly age-standardized incidence rates (ASIRs) of cancers. We evaluated level and trend changes using interventional autoregressive integrated moving average models. Secondary outcomes were the proportion of patients who were enrolled in a clinical trial, who had metastatic or advanced disease and who died within 30 days. We compared the baseline and pandemic periods using rate ratios (RRs) and 95% confidence intervals (CIs).Results: Age-standardized incidence rates during COVID-19 quarters were 157.7, 164.6, and 148.0 per million, respectively, whereas quarterly baseline ASIRs ranged between 150.3 and 175.1 per million (incidence RR 0.93 [95% CI 0.78 to 1.12] to incidence RR 1.04 [95% CI 0.87 to 1.24]). We found no statistically significant level or slope changes between the projected and observed ASIRs for all new cancers (parameter estimate [β], level 4.98, 95% CI -15.1 to 25.04, p = 0.25), or when stratified by cancer type or by geographic area. Clinical trial enrolment rate was stable or increased during the pandemic compared with baseline (RR 1.22 [95% CI 0.70 to 2.13] to RR 1.71 [95% CI 1.01 to 2.89]). There was no difference in the proportion of patients with metastatic disease (RR 0.84 [95% CI 0.55 to 1.29] to RR 1.22 [0.84 to 1.79]), or who died within 30 days (RR 0.16 [95% CI 0.01 to 3.04] to RR 1.73 [95% CI 0.38 to 15.2]).Interpretation: We did not observe a statistically significant change in the incidence of childhood cancer, or in the proportion of children enrolling in a clinical trial, presenting with metastatic disease or who died early during the first 9 months of the COVID-19 pandemic, which suggests that access to health care in pediatric oncology was not reduced substantially in Canada. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to describe the impact of trial enrollment at diagnosis on event-free and overall survival in paediatric acute lymphoblastic leukaemic (ALL) using a population-based approach.Methods: We conducted a retrospective cohort study that included children newly diagnosed with ALL between 1 and 14 years of age. The data source was the Cancer in Young People in Canada (CYP-C) national paediatric cancer population-based database. We conducted univariate and multiple Cox proportional hazards models.Results: There were 2569 children with ALL; 1408 (54.8%) were enrolled on a clinical trial at initial diagnosis. Event-free survival at 5 years was 89.8%±0.9 vs 84.1%±1.2. (P<0.0001) for those enrolled and not enrolled on a clinical trial, respectively. Overall survival at 5 years was higher for those enrolled (94.1%±0.7) vs not enrolled (90.5%±1.0; P=0.001). In a model that adjusted for demographic, leukaemic and socioeconomic factors, enrollment on trials was significantly associated with better event-free survival (hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.47-0.95; P=0.023), but not overall survival (HR 0.69, 95% CI 0.44-1.08; P=0.102).Conclusions: Event-free survival was significantly better in children with ALL enrolled on a clinical trial. Future research should identify barriers to clinical trial enrollment for children with ALL. [ABSTRACT FROM AUTHOR]

Background: Primary objective was to describe the proportion of children newly diagnosed with cancer enrolled on a therapeutic clinical trial. Secondary objectives were to describe reasons for non-enrollment and factors associated with enrollment on trials.Methods: In this retrospective cohort study, we included children newly diagnosed with cancer between 0 and 14 years of age and diagnosed from 2001 to 2012. We used data from the Cancer in Young People in Canada (CYP-C) national pediatric cancer population-based database. CYP-C captures all cases of pediatric cancer (0-14 years) diagnosed and treated at one of the 17 tertiary pediatric oncology centers in Canada. Non-enrollment was evaluated using univariate and multiple logistic regression analysis.Results: There were 9204 children with cancer included, of whom 2533 (27.5%) were enrolled on a clinical trial. The most common reasons cited for non-enrollment were lack of an available trial (52.2%) and physician choice (11.2%). In multiple regression, Asian and Arab/west Asian race were associated with lower enrollment (P = 0.006 and P = 0.032 respectively). All cancer diagnoses were more likely to be enrolled compared to astrocytoma and children with acute lymphoblastic leukemia had an almost 18-fold increased odds of enrollment compared to astrocytoma (P < 0.0001). Greater distance from the tertiary care center was independently associated with non-enrollment (P < 0.0001).Conclusions: In Canada, 27.5% of children with cancer are enrolled onto therapeutic clinical trials and lack of an available trial is the most common reason contributing to non-enrollment. Future research should better understand reasons for lack of trial availability and physician preferences to not offer trials. [ABSTRACT FROM AUTHOR]

Background Fatigue is an important problem in paediatric cancer patients and yoga may be an effective intervention. The primary objective was to determine the feasibility of individualized yoga for hospitalized children receiving intensive chemotherapy. Methods We included English-speaking children and adolescents aged 7-18 years receiving intensive chemotherapy or haematopoietic stem cell transplantation (HSCT). Yoga was conducted three times weekly for three weeks. The primary outcome was feasibility, defined as ability to deliver at least 60% of planned sessions. Secondary outcomes were parent-reported Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale, Fatigue Scale-Parent, PedsQL Generic Core Scales and PedsQL Acute Cancer Module. Results Between January and October 2013, 11 patients were enrolled. Median age was 14.0 (range 7.7-16.4) years and 6 (55%) were boys. Yoga was feasible with 10/11 participants meeting the threshold for feasibility. The median number of yoga sessions was 9 (range 3-13). No adverse events were attributed to yoga. Mean ± standard deviation for the day 21 proxy-reported PedsQL general fatigue scores was 55.6 ± 15.5. Qualitative comments suggested design changes for future yoga studies. Conclusions Individualized yoga is feasible for inpatient children receiving intensive chemotherapy. Future work will include development and conduct of a randomized trial for fatigue amelioration. [ABSTRACT FROM AUTHOR]

BACKGROUND Pediatric cancer distribution and outcomes have not been examined in Canadian Aboriginal children. The objective of this study was to describe the distribution, event-free survival, and overall survival of Aboriginal children with malignancies who reside in Ontario compared with non-Aboriginal children. METHODS This population-based study included 10,520 Ontario children (aged <18 years) who were diagnosed with cancer between 1985 and 2011. Patients were identified from the Pediatric Oncology Group of Ontario Networked Information System database. Aboriginal children were identified by self-reported ethnicity or postal code on a Native reserve at diagnosis. Descriptive statistics of the patients were presented and compared using the Fisher exact test. Event-free and overall survival probabilities were calculated for Aboriginal and non-Aboriginal children, described using Kaplan-Meier curves, and compared using log-rank tests. RESULTS In total, 65 Aboriginal children and 10,364 non-Aboriginal children with malignancy were identified. The distribution of malignancy type was similar between the 2 groups. There were no significant differences in baseline characteristics, presence of metastatic disease, or treatment approach (clinical trial, standard of care, or individualized protocol) between the groups. The 5e-year event-free survival rate (± standard error) was 56.3% ± 6.2% among Aboriginal children versus 72.8% ± 0.4% among non-Aboriginal children ( P = .0042), and the 5-year overall survival rate was 64% ± 6.0% versus 79.3 ± 0.4% ( P = .0017), respectively. The cause of death did not vary according to Aboriginal ethnicity. CONCLUSIONS Survival was significantly inferior among Aboriginal children who had cancer compared with non-Aboriginal children who had cancer in Ontario. Future studies are required to define the etiology of this disparity, evaluate the issue nationally, and create interventions to improve outcomes for Aboriginal children. Cancer 2014;120:2751-2759. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: It is not known whether children with acute promyelocytic leukemia (APL) have an infection risk similar to non- APL acute myeloid leukemia. The objective was to describe infectious risk in children with newly diagnosed APL and to describe factors associated with these infections. Methods: We conducted a retrospective, population-based cohort study that included children = 18 years of age with de novo APL treated at 15 Canadian centers. Thirty-three children with APL were included; 78.8% were treated with APL -specific protocols. Results: Bacterial sterile site infection occurred in 12 (36.4%) and fungal sterile site infection occurred in 2 (6.1%) children. Of the 127 chemotherapy courses, 101 (79.5%) were classified as intensive and among these, the proportion in which a sterile site microbiologically documented infection occurred was 14/101 (13.9%). There was one infection-related death. Conclusions: One third of children with APL experienced at least one sterile site bacterial infection throughout treatment and 14% of intensive chemotherapy courses were associated with a microbiologically documented sterile site infection. Infection rates in pediatric APL may be lower compared to non- APL acute myeloid leukemia although these children may still benefit from aggressive supportive care during intensive chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Children with Down syndrome (DS) are at high risk of infectious toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols optimized in children without DS. Our objective was to determine if children with DS and acute myeloid leukemia (AML) have a different risk of infection when treated with chemotherapy protocols developed for children with DS compared to AML treatment protocols developed for children without DS. Methods: We conducted a retrospective, population-based cohort study that included DS children ? 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, and treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease or death (whichever occurred first). Trained research associates abstracted all information from each site. Results: There were 31 children with DS included; median age was 1.7 (range 0.1-11.1) years. Eleven were treated according to a DS-specific protocol while 20 were treated with non-DS specific protocols. A total of 157 courses of chemotherapy were delivered. Microbiologically documented sterile site infection occurred in 11.9% and 14.3% of DS-specific and non-DS specific AML treatment courses respectively. Sepsis was rare and there were no infection-related deaths. In multiple regression, treatment with a DS-specific protocol was independently associated with a reduction in microbiologically documented sterile site infection (adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42-0.99; P = 0.044), and clinically documented infection (adjusted OR 0.36, 95% CI 0.14-0.91; P = 0.031) but not bacteremia (adjusted OR 0.73, 95% CI 0.44-1.22; P = 0.231). Conclusions: Our study suggests that children with DS do not experience excessive infectious toxicity during treatment for AML compared to children without DS. Incorporation of DS-specific AML treatment protocols is associated with a more favorable infection profile for children with DS-AML. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Tran et al. (2012) Pandemic (H1N1) 2009 influenza in Canadian pediatric cancer and hematopoietic stem cell transplant patients. Influenza and Other Respiratory Viruses 6(601), e105-e113. Background The impact of pandemic H1N1 influenza (pH1N1) virus in pediatric cancer is uncertain. The objectives of this study were to characterize the clinical course of pH1N1 and identify factors associated with severe outcomes. Methods We conducted a Canadian multicenter retrospective review of children with cancer and stem cell transplant (SCT) recipients who were diagnosed with laboratory-confirmed pH1N1 infection between May 1, 2009 and January 31, 2010. Results We identified 100 (19 in wave 1 and 81 in wave 2) cases of pH1N1 infection. Median age was 8·7 years. 71% had a hematologic malignancy, and 20% received SCT. Median duration of fever and illness was 2 and 12·5 days, respectively. 51 (51·5%) were hospitalized for a median of 5 days, with no deaths and only 1 requiring admission to the intensive care unit. Radiologically confirmed pneumonia was diagnosed in 10 (10%). Interruption of chemotherapy or conditioning occurred in 43 patients. In multivariable analyses, age <5 years (relative to ≥10 years) and neutropenia were associated with hospitalization while neutropenia was associated with pneumonia. Despite oseltamivir use in 89%, viral shedding was prolonged (median, 46 days) and often persisted after symptom resolution. However, an extended treatment course (>5 days) correlated with shortened duration of viral shedding ( P = 0·041). Conclusions pH1N1 infection in pediatric cancer and SCT patients infrequently caused complications but commonly interrupted cancer treatment. Persistent shedding of virus after illness resolution was common. Further research is needed to verify this finding as it could have implications for treatment guidelines and infection control practices. [ABSTRACT FROM AUTHOR]

Background: Given the increasing numbers of immigrant families in Canada, it is imperative that healthcare providers (HCPs) understand the caregiving experiences of immigrant family caregivers. Our study aimed to explore any special challenges faced by immigrant parents of children with cancer and to identify supportive factors. Methods: A constructivist grounded theory approach was used. Participants included 50 first generation Chinese and South Asian parents of children with cancer who were at least six months post-diagnosis. Recruitment took place at six Canadian pediatric oncology centres. Interviews were conducted in English, Cantonese, Mandarin, Urdu, Punjabi or Hindi. Analysis involved coding and the use of the constant comparison method. Interviewing continued until no new themes emerged. Results: While immigrant parents described many challenges faced by any parent of a child with cancer, the context of being an immigrant made certain experiences particularly challenging. Parents described challenges in the following areas: managing caregiving demand and financial strain, accessing support from others, and interfacing with the healthcare system. Parents described receiving a range of practical, emotional, social and informational support from extended family, their workplace, other cancer families, community organizations and HCPs. Conclusions: Our study addresses an important gap in the research literature by providing practical insight into the experiences of immigrant family caregivers. Our findings may help to inform the development of pediatric oncology policies and programs in ways that respond to the unique needs and challenges of culturally and linguistically diverse families. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVE. Private cord blood banks are for-profit companies that facilitate storage of umbilical cord blood for personal or family use. Pediatric hematopoietic cell transplantation physicians are currently best situated to use cord blood therapeutically. We sought to describe the experiences and views of these physicians regarding private cord blood banking. PARTICIPANTS AND METHODS. We e-mailed a cross-sectional survey to pediatric hematopoietic cell transplantation physicians in the United States and Canada; 93 of 152 potentially eligible physicians (93 of 130 confirmed survey recipients) from 57 centers responded. Questions addressed the number of transplants performed by using privately banked cord blood, willingness to use banked autologous cord blood in specific clinical settings, and recommendations to parents regarding private cord blood banking. RESULTS. Respondents reported having performed 9 autologous and 41 allogeneic transplants using privately banked cord blood. In 36 of 40 allogeneic cases for which data were available, the cord blood had been collected because of a known indication in the recipient. Few respondents would choose autologous cord blood over alter- native stem cell sources for treatment of acute lymphoblastic leukemia in second remission. In contrast, 55% would choose autologous cord blood to treat high-risk neuroblastoma, or to treat severe aplastic anemia in the absence of an available sibling donor. No respondent would recommend private cord blood banking for a newborn with 1 healthy sibling when both parents were of northern European descent; 11 % would recommend banking when parents were of different minority ethnicities. CONCLUSIONS. Few transplants have been performed by using cord blood stored in the absence of a known indication in the recipient. Willingness to use banked autologous cord blood varies depending on disease and availability of alternative stem cell sources. Few pediatric hematopoietic cell transplantation physicians endorse private cord blood banking in the absence of an identified recipient, even for mixed-ethnicity children for whom finding a suitably matched unrelated donor may be difficult. [ABSTRACT FROM AUTHOR]

• Access to HSCT is largely governed by biologic disease-related factors. • In a publically funded health system, children with ALL had equitable access to HSCT. • Socioeconomic factors (income and race) did not have any effect on receipt of HSCT. • Patients diagnosed at an HSCT performing center were more likely to access HSCT. Access to hematopoietic stem cell transplantation (HSCT) in pediatric acute lymphoblastic leukemia (ALL) primarily depends on disease-related factors but may be influenced by social and economic determinants. We included all children aged < 15 years with newly diagnosed ALL in Canada between 2001 and 2018 using the Cancer in Young People in Canada national registry. We examined factors potentially associated with the likelihood of receiving HSCT using univariate and multivariable logistic regression models. A total of 3992 patients with newly diagnosed ALL were included. Three hundred twenty-five (8.1%) received an HSCT and formed the transplant cohort. In multivariable analysis factors independently associated with an increased odds of receiving HSCT were male sex (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.05 to 1.93), initial WBC ≥ 50,000 × 109/L (OR, 1.58; 95% CI, 1.09 to 2.28), mixed phenotype acute leukemia relative to B-precursor ALL (OR, 34.32; 95% CI, 16.64 to 70.79), T cell relative to B-precursor ALL (OR, 1.77; 95% CI, 1.07 to 2.91), unfavorable relative to standard cytogenetics (OR, 3.96; 95% CI, 2.56 to 6.12), and relapse before HSCT (OR, 32.77; 95%, 23.89 to 44.96). No association was found between race, neighborhood income quintile or region at diagnosis, and receipt of HSCT. Diagnosis at an HSCT treating center (OR, 1.51; 95% CI, 1.09 to 2.09) and residential distance from the ALL treating center (OR, 1.84 for ≥300 km compared with <100 km; 95% CI, 1.17 to 2.91) were associated with higher odds of receiving HSCT. In a publically funded healthcare system, children with ALL had equitable access to HSCT, which was largely governed by biologic disease-related factors. Patients diagnosed at an HSCT performing center and patients who live farthest away from their treatment center had higher odds of receiving HSCT, although the effect was small, possibly suggesting preferential referral to HSCT for some patients. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the expected value of undertaking a future randomized controlled trial of thresholds used to initiate invasive ventilation compared with usual care in hypoxemic respiratory failure., Perspective: Publicly funded healthcare payer., Setting: Critical care units capable of providing invasive ventilation and unconstrained by resource limitations during usual (nonpandemic) practice., Methods: We performed a model-based cost-utility estimation with individual-level simulation and value-of-information analysis focused on adults, admitted to critical care, receiving noninvasive oxygen. In the primary scenario, we compared hypothetical threshold A to usual care, where threshold A resulted in increased use of invasive ventilation and improved survival compared with usual care. In the secondary scenario, we compared hypothetical threshold B to usual care, where threshold B resulted in decreased use of invasive ventilation and similar survival compared with usual care. We assumed a willingness-to-pay of 100,000 Canadian dollars (CADs) per quality-adjusted life year., Results: In the primary scenario, threshold A was cost-effective compared with usual care due to improved hospital survival (78.1% vs. 75.1%), despite more use of invasive ventilation (62% vs. 30%) and higher lifetime costs (86,900 vs. 75,500 CAD). In the secondary scenario, threshold B was cost-effective compared with usual care due to similar survival (74.5% vs. 74.6%) with less use of invasive ventilation (20.2% vs. 27.6%) and lower lifetime costs (71,700 vs. 74,700 CAD). Value-of-information analysis showed that the expected value to Canadian society over 10 years of a 400-person randomized trial comparing a threshold for invasive ventilation to usual care in hypoxemic respiratory failure was 1.35 billion CAD or more in both scenarios., Conclusions: It would be highly valuable to society to identify thresholds that, in comparison to usual care, either increase survival or reduce invasive ventilation without reducing survival., Competing Interests: Dr. Yarnell was funded by the Canadian Institutes for Health Research Vanier Scholar program, the Eliot Phillipson Clinician Scientist Training Program, and the Clinician Investigator Program of the University of Toronto. Dr. Heath is supported by a Canada Research Chair in Statistical Trial Design and funded by the Discovery Grant Program of the Natural Sciences and Engineering Research Council of Canada (RGPIN-2021-03366). Dr. Sung is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. Dr. Fowler is the H. Barrie Fairley Professor of Critical Care at the University Health Network, Interdepartmental Division of Critical Care Medicine, and University of Toronto. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Classification 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. Twenty-two patients with uIBMFSs and 70 patients with classified IBMFSs underwent HSCT. Five-year overall survival of uIBMFS patients after HSCT was inferior to that of patients with classified IBMFSs (56% vs 76.5%). The outcome of patients with uIBMFS who received cord blood was significantly lower than that of patients who received other stem cell sources (14.8% vs 90.9%). Engraftment failure was higher among patients with uIBMFS who received cord blood than those who received bone marrow. None of the following factors were significantly associated with poor survival: transfusion load, transplant indication, the intensity of conditioning regimen, human leukocyte antigen-identical sibling/alternative donor. We suggest that identifying the genetic diagnosis is essential to modulate the transplant procedure including conditioning agents and stem cell sources for better outcome and the standard cord blood transplantation (CBT) should be avoided in uIBMFS., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Delay in diagnosis and treatment initiation can be associated with adverse outcomes in children with cancer. Diagnostic interval (DI) is defined as the time between the date of first health care contact for symptoms related to cancer to the date of cancer diagnosis, and treatment interval (TI) is defined as interval between the definitive cancer diagnosis and cancer treatment initiation. We aimed to determine the predictors of DI and TI in children with rhabdomyosarcoma (RMS) and their association with event-free survival (EFS) and overall survival (OS)., Methods: Using the Cancer in Young People in Canada (CYP-C) national population-based database, we conducted a retrospective cohort study of children (0-14.99 years) newly diagnosed with RMS between 2001 and 2015 in Canada. Quantile regression was used to assess the predictors of DI and TI, and Cox regression was used to determine if these intervals were associated with EFS and OS., Results: Median DI and TI were 16.5 days (interquartile range [IQR] 6.0-38.0) and 5 days (IQR 0-12), respectively. DI and TI were not significantly associated with age at diagnosis, sex, race, tumor site, stage or histology, treatment region, distance from treatment center, income quintile or diagnosis year (all p > .05). DI and TI were not associated with EFS (DI: hazard ratio [HR] 1.00, 95% CI 0.96-1.05, p = .871; TI: HR 1.03, 95% CI 1.00-1.05, p = .053) or OS (DI: HR 0.99, 95% CI 0.94-1.05, p = .797; TI: HR 1.02, 95% CI 0.99-1.05, p = .155)., Conclusions: In the publicly funded Canadian health care system, DI and TI did not affect the survival of children with RMS., (© 2021 Wiley Periodicals LLC.)

Background: The COVID-19 pandemic has had a major impact on access to health care resources. Our objective was to estimate the impact of the COVID-19 pandemic on the incidence of childhood cancer in Canada. We also aimed to compare the proportion of patients who enrolled in clinical trials at diagnosis, presented with metastatic disease or had an early death during the first 9 months of the COVID-19 pandemic compared with previous years., Methods: We conducted an observational study that included children younger than 15 years with a new diagnosis of cancer between March 2016 and November 2020 at 1 of 17 Canadian pediatric oncology centres. Our primary outcome was the monthly age-standardized incidence rates (ASIRs) of cancers. We evaluated level and trend changes using interventional autoregressive integrated moving average models. Secondary outcomes were the proportion of patients who were enrolled in a clinical trial, who had metastatic or advanced disease and who died within 30 days. We compared the baseline and pandemic periods using rate ratios (RRs) and 95% confidence intervals (CIs)., Results: Age-standardized incidence rates during COVID-19 quarters were 157.7, 164.6, and 148.0 per million, respectively, whereas quarterly baseline ASIRs ranged between 150.3 and 175.1 per million (incidence RR 0.93 [95% CI 0.78 to 1.12] to incidence RR 1.04 [95% CI 0.87 to 1.24]). We found no statistically significant level or slope changes between the projected and observed ASIRs for all new cancers (parameter estimate [β], level 4.98, 95% CI -15.1 to 25.04, p = 0.25), or when stratified by cancer type or by geographic area. Clinical trial enrolment rate was stable or increased during the pandemic compared with baseline (RR 1.22 [95% CI 0.70 to 2.13] to RR 1.71 [95% CI 1.01 to 2.89]). There was no difference in the proportion of patients with metastatic disease (RR 0.84 [95% CI 0.55 to 1.29] to RR 1.22 [0.84 to 1.79]), or who died within 30 days (RR 0.16 [95% CI 0.01 to 3.04] to RR 1.73 [95% CI 0.38 to 15.2])., Interpretation: We did not observe a statistically significant change in the incidence of childhood cancer, or in the proportion of children enrolling in a clinical trial, presenting with metastatic disease or who died early during the first 9 months of the COVID-19 pandemic, which suggests that access to health care in pediatric oncology was not reduced substantially in Canada., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

There are conflicting data about whether the development of cancer-associated thrombo-embolism (TE) negatively impacts survival in children. The objective was to determine whether TE during treatment was associated with overall survival (OS) and event-free survival (EFS) in children with acute lymphoblastic leukemia (ALL). We performed a population-based retrospective cohort study using the Cancer in Young People-Canada registry. Children <15 years of age were diagnosed with de novo ALL (2000-2016). The primary exposure variable was radiologically-confirmed thrombo-embolism requiring medical intervention. Multivariable Cox regression models were used to determine the impact of thrombo-embolism on survival, where TE was time-dependent. We included 2006 children (median age: 4 years, 88.5% precursor B-cell ALL). Thrombo-embolism occurred in 113 patients (5.6%), at a median time of 107 days (interquartile range: 35-184 days) after ALL diagnosis. Among standard/low-risk patients, 41/1165 (3.5%) developed TE while among high/very high-risk patients, 72/841 (8.6%) developed TE. Patients with TE had a significantly worse OS (adjusted HR [aHR] of death: 2.61, 95% CI: 1.62-4.22, p < 0.001) and EFS (aHR of an event [death, relapse, second malignancy]: 2.03, 95% CI: 1.35-3.05, p = 0.001), compared with patients without TE. No statistically significant difference was seen in standard/low risk ALL for OS and EFS, but TE was associated with a significantly lower OS and EFS in children with high/very high-risk ALL (aHR of death: 2.90, 95% CI: 1.79-4.72, p < 0.001; aHR of an event: 2.02, 95% CI: 1.30-3.12, p = 0.002). Thus, TE led to a statistically significant reduction in OS and EFS in children with high risk/very high-risk leukemia., (© 2021 Wiley Periodicals LLC.)

Background: While impressive gains in childhood cancer survival have been reported both in Canada and internationally, it has been almost 15 years since the last comprehensive evaluation of Canadian data., Data and Methods: Data are from the population-based Canadian Cancer Registry, record-linked to the Canadian Vital Statistics Death database. Children aged 0 to 14 diagnosed with new primary malignant cancers from 1992 to 2017 in Canada except Quebec were included. Overall survival was measured using observed survival proportions (OSPs). Estimates for the 2013-to-2017 period were predicted using the period method; otherwise, the cohort method was used., Results: For the 2013-to-2017 period, five-year OSPs were at least 90% for 10 of 24 individual cancer groups or subgroups reported. Survival was highest for thyroid carcinomas (100%) and Hodgkin lymphomas (99%) and lowest for other gliomas (42%). A significant increase in the five-year OSP from the 1992-to-1996 period (77%) to the 2013-to-2017 period (84%) was observed for all childhood cancers combined, but not since the 2003-to-2007 period. The greatest increase was for chronic myeloproliferative diseases (35.4 percentage points); for lymphoid leukemias, survival increased from 85% to 93%. Survival was relatively poor at baseline for hepatic tumours, malignant bone tumours, and soft tissue and other extraosseous sarcomas, and it remained virtually unchanged. Once children survived five years, the probability of surviving another five years exceeded 95% across most diagnoses., Discussion: Significant improvements in both short- and long-term paediatric cancer survival have been made in Canada since the early to mid-1990s. These findings are clinically meaningful and are likely to be reassuring to families.

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., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

An infectious trigger for childhood acute lymphoblastic leukemia is hypothesized and we assessed the association between the rate, type, and critical exposure period for infections and the development of acute lymphoblastic leukemia. We conducted a matched case-control study using administrative databases to evaluate the association between the rate of infections and childhood acute lymphoblastic leukemia diagnosed between the ages of 2-14 years from Ontario, Canada and we used a validated approach to measure infections. In 1600 cases of acute lymphoblastic leukemia, and 16 000 matched cancer-free controls aged 2-14 years, having >2 infections/year increased the odds of childhood acute lymphoblastic leukemia by 43% (odds ratio = 1.43, 95% confidence interval 1.13-1.81) compared to children with ≤0.25 infections/year. Having >2 respiratory infections/year increased odds of acute lymphoblastic leukemia by 28% (odds ratio =1.28, 95% confidence interval 1.05-1.57) compared to children with ≤0.25 respiratory infections/year. Having an invasive infection increased the odds of acute lymphoblastic leukemia by 72% (odds ratio =1.72, 95% confidence interval 1.31-2.26). Having an infection between the age of 1-1.5 years increased the odds of acute lymphoblastic leukemia by 20% (odds ratio = 1.20, 95% confidence interval 1.04-1.39). Having more infections increased the odds of developing childhood acute lymphoblastic leukemia and having an infection between the ages of 1-1.5 years increased the odds of childhood acute lymphoblastic leukemia.

Introduction: Indications for hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML) are primarily dependent on risk stratification at diagnosis and relapse status. We sought to determine whether access to HSCT is influenced by regional and socioeconomic factors., Methods: Children with newly diagnosed AML aged < 15 years between 2001 and 2015 were identified using the Cancer in Young People in Canada national population-based registry. Factors potentially associated with the receipt of HSCT were studied using univariate and multivariable logistic regression models., Results: Overall, 568 children with newly diagnosed AML were included and 262 (46%) received HSCT. A greater proportion of patients, 103/157 (65.6%), underwent HSCT after first or subsequent relapse compared to 159/411 (38.7%) patients who underwent transplant before relapse. Among patients for whom HSCT would be considered before relapse, factors associated with higher odds of HSCT in a multivariable analysis were: poor versus good-risk cytogenetics (Odds ratio [OR]: 30.0, 95% confidence interval [CI]: 7.7-117.0), diagnosis during 2012-2015 versus 2001-2006 (OR: 3.2, 95% CI: 1.6-6.3), diagnosis in eastern Canada versus central Canada (OR: 3.7, 95% CI: 1.9-7.3), and age 10-14 years versus age < 1 year (OR: 5.4, 95% CI: 2.3-12.8). Among patients for whom HSCT would be considered after first relapse, higher odds of HSCT was associated with diagnosis at a HSCT center (OR: 2.1, 95% CI: 1.1-4.1)., Conclusion: Patients diagnosed at a HSCT performing center and patients from eastern Canada had higher odds of receiving HSCT. This may suggest preferential access to HSCT for certain patients., (© 2020 Wiley Periodicals, Inc.)

Progressive 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.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: Symptom Screening in Pediatrics Tool (SSPedi) is a validated approach to measuring bothersome symptoms for English-speaking and Spanish-speaking children with cancer and paediatric haematopoietic stem cell transplantation (HSCT) recipients. Objectives were to translate SSPedi into French, and among French-speaking children receiving cancer treatments, to evaluate understandability and cultural relevance., Methods: We conducted a multiphase, descriptive study to translate SSPedi into French. Forward translation was performed by four medical translators. After confirming that back translation was satisfactory, we enrolled French-speaking children with cancer and paediatric HSCT recipients at four centres in France and Canada., Primary and Secondary Outcome Measures: Understandability was evaluated by children themselves who self-reported degree of difficulty, and by two adjudicators who rated incorrectness. Assessment of cultural relevance was qualitative. Participants were enrolled in cohorts of 10., Results: There were 30 children enrolled. Participants were enrolled from Marseille (n=10, 33%), Ottawa (n=1, 3%), Quebec City (n=11, 37%) and Toronto (n=8, 27%). No child reported that it was hard or very hard to complete French SSPedi in the last cohort of 10 participants. Changes to the instrument itself were not required. After enrolment of 30 respondents, the French translation of SSPedi was considered finalised based on self-reported difficulty with understanding, adjudicated incorrect understanding and cultural relevance., Conclusions: We translated and finalised SSPedi for use by French-speaking children and adolescents receiving cancer treatments. Future work should begin to use the translated version to conduct research and to facilitate clinical care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Associations between body mass index (BMI), outcome, and leukemia-related factors in children with acute myeloid leukemia (AML) remain unclear. We investigated associations between pretherapeutic BMI, cytogenetic abnormalities, and outcome in a large multinational cohort of children with AML., Methods: We included patients, age 2-17 years, diagnosed with de novo AML from the five Nordic countries (2004-2016), Hong Kong (2007-2016), the Netherlands and Belgium (2010-2016), and Canada and USA (1995-2012). BMI standard deviations score for age and sex was calculated and categorized according to the World Health Organization. Cumulative incidence functions, Kaplan-Meier estimator, Cox regression, and logistic regression were used to investigate associations., Results: In total, 867 patients were included. The median age was 10 years (range 2-17 years). At diagnosis, 32 (4%) were underweight, 632 (73%) were healthy weight, 127 (15%) were overweight, and 76 (9%) were obese. There was no difference in relapse risk, treatment-related mortality or overall mortality across BMI groups. The frequency of t(8;21) and inv(16) increased with increasing BMI. For obese patients, the sex, age, and country adjusted odds ratio of having t(8;21) or inv(16) were 1.9 (95% confidence interval (CI) 1.1-3.4) and 2.8 (95% CI 1.3-5.8), respectively, compared to healthy weight patients., Conclusions: This study did not confirm previous reports of associations between overweight and increased treatment-related or overall mortality in children. Obesity was associated with a higher frequency of t(8;21) and inv(16). AML cytogenetics appear to differ by BMI status., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: There is a growing need to assess the long-term quality of life (QOL) of pediatric oncology patients since many children now survive their disease. This paper highlights the subjective perspectives of pediatric cancer patients and specifically explores how experiencing cancer at a young age impacts adolescents in the areas of social functioning, peer relationships, and QOL. The findings emerged from a qualitative research study that explored how pediatric oncology patients ascribe meaning to their illness., Methods: Study participants were recruited from four Canadian academic pediatric hospitals. In this study, we used an interpretative description approach. Semistructured interviews were completed, transcribed verbatim, and coded through the method of constant comparison., Results: A total of 37 children and adolescents (n = 19 female; 51%) participated. The majority of participants were diagnosed with leukemia (n = 16; 43%) or lymphoma (n = 9; 24%). Sixty-two percent of participants were adolescents between the ages of 13 and 18 years (n = 23). Data illustrated a unique adolescent experience, which has been reported as a subset of the original population. Adolescent participants noted an accelerated experience of maturation, which invited reflections of gratitude as well as feelings of isolation and disconnect from peers. Participants were saddened to have "missed out" on normative parts of childhood., Conclusion: Findings highlighted experiences of accelerated maturity that prompted adverse social outcomes for adolescent participants, which impacted their QOL. Future research is needed to explore the intersection of accelerated maturity attributed to illness, social functioning, and QOL. Peer support through technology engagement is suggested for this population., (© 2019 John Wiley & Sons, Ltd.)

There is conflicting information about the epidemiology of thromboembolism (TE) in paediatric oncology. Objectives were to describe the incidence and risk factors of TE in children with cancer. We included all children with cancer less than 15 years of age diagnosed from 2001 to 2016, treated at one of the 12 Canadian paediatric centres outside of Ontario and entered into the Cancer in Young People-Canada database. Potential risk factors for TE were evaluated using Cox proportional hazards regression stratified by haematological malignancies versus solid tumours. Factors associated with vascular access- and non-vascular access-related TE were compared using chi-square or Fisher's exact tests. Of the 7,471 children included, 283 experienced TE requiring medical intervention; cumulative incidence of TE at 5 years was 3.8 ± 0.2% and 0.36% ± 0.07% for life-threatening or fatal TE. For haematological malignancies, the following factors were associated with TE in multivariable regression: age < 1 year, 5 to 9.99 years and 10 to 14.99 years (relative to age 1-4.99 years), haematopoietic stem cell transplant (hazard ratio [HR] = 1.49, 95% confidence interval [CI], 1.00-2.32), anthracyclines (HR = 2.21, 95% CI, 1.12-4.37) and asparaginase (HR = 1.68, 95% CI, 1.15-2.44). For solid tumours, obesity (HR = 1.92, 95% CI, 1.01-3.68), surgery (HR = 2.70, 95% CI, 1.44-5.08), radiation (HR = 47.51, 95% CI, 24.01-94.01), anthracyclines (HR = 2.74, 95% CI, 1.29-5.82) and platinum agents (HR = 2.26, 95% CI, 1.19-4.28) were associated with TE. Life-threatening and fatal TEs were more common among non-vascular access TEs (14.5% vs. 3.3% p  = 0.001). In a population-based cohort, 4% of children with cancer developed a clinically significant TE. Accurate risk stratification tools are needed specific to malignancy type., Competing Interests: None of the authors have competing interest to disclose. Dr. Marie-Claude Pelland-Marcotte's fellowship at the Hospital for Sick Children (Toronto, Canada) was supported by Shire Endowment Fund for Training in Pediatric Hemostasis., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives were to describe any bothersome symptom and severely bothersome symptoms in inpatient children with cancer and hematopoietic stem cell transplant (HSCT) recipients. We included children 8-18 years of age with cancer or HSCT recipients who were receiving active treatment for cancer, admitted to hospital, and expected to be in hospital 3 days later. We administered the self-report Symptom Screening in Pediatrics Tool (SSPedi). We described those who identified any degree of symptom bother (at least "a little") and those who rated the degree of bother as severe ("a lot" or "extremely"). Factors associated with severe symptoms and total SSPedi scores were examined using multiple logistic and linear regression. Among the 302 patients, 298 (98.7%) reported having any bothersome symptom and 181 (59.9%) had at least one severely bothersome symptom. In multiple regression, older children were significantly more likely to have at least one severely bothersome symptom (15-18 and 11-14 years vs. 8-10 years; P = 0.008) and to have higher total SSPedi scores (P = 0.0003). Those with relapsed disease were more likely to have at least one severely bothersome symptom (odds ratio 2.1, 95% confidence interval 1.1-4.3; P = 0.037) and HSCT recipients were more likely to have higher symptom scores (β = 3.48, standard error = 1.6; P = 0.030). Almost all children receiving cancer therapies experience bothersome symptoms and 60% have at least one severely bothersome symptom. Older children experienced more severely bothersome symptoms and higher symptom scores. Future studies should follow children longitudinally to better understand the symptom trajectory and should institute interventions to manage symptoms., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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.

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., (Copyright© Ferrata Storti Foundation.)

Background: Despite the success of central nervous system (CNS) directed therapy in pediatric acute lymphoblastic leukemia (ALL), relapse involving the CNS continues to be observed in 5-10% of children when utilizing standard intrathecal prophylactic chemotherapy. While most pediatric ALL treatment protocols mandate regular lumbar punctures (LP) for the intrathecal injection of chemotherapy, the value of routine cytological analysis of cerebrospinal fluid (CSF) during therapy is unknown. Our objective was to assess the diagnostic value of routine CSF analysis during ALL therapy., Procedure: To allow for at least 10 years of follow up from ALL diagnosis, children (0-18 years) with ALL diagnosed and treated at SickKids, Toronto, Canada between 1994-2004 were studied. Medical records of patients with CNS relapse were examined to determine whether CNS relapse was diagnosed based on cytology of a routinely obtained CSF sample, a CSF sample obtained because of signs and symptoms or a CSF sample obtained after the diagnosis of a bone marrow relapse., Results: Of 494 children treated for ALL, 31 (6.6%) developed a relapse of ALL involving the CNS. Twenty-two had an isolated CNS relapse and nine had a combined bone marrow and CNS relapse. Among patients with isolated CNS relapse, 73% (16/22) were diagnosed based on routine CSF samples obtained from asymptomatic children. Conversely, 89% (8/9) of children with combined bone marrow and CNS relapse presented with symptoms and signs that prompted CSF examination., Conclusion: Routine CSF examination at the time of LP for intrathecal chemotherapy is useful in detecting CNS relapse., (© 2014 Wiley Periodicals, Inc.)

Purpose: To improve survival rates in children with acute myeloid leukemia (AML), we evaluated gemtuzumab-ozogamicin (GO), a humanized immunoconjugate targeted against CD33, as an alternative to further chemotherapy dose escalation. Our primary objective was to determine whether adding GO to standard chemotherapy improved event-free survival (EFS) and overall survival (OS) in children with newly diagnosed AML. Our secondary objectives examined outcomes by risk group and method of intensification., Patients and Methods: Children, adolescents, and young adults ages 0 to 29 years with newly diagnosed AML were enrolled onto Children’s Oncology Group trial AAML0531 and then were randomly assigned to either standard five-course chemotherapy alone or to the same chemotherapy with two doses of GO (3 mg/m2/dose) administered once in induction course 1 and once in intensification course 2 (two of three)., Results: There were 1,022 evaluable patients enrolled. GO significantly improved EFS (3 years: 53.1% v. 46.9%; hazard ratio [HzR], 0.83; 95% CI, 0.70 to 0.99; P.04) but not OS (3 years: 69.4% v. 65.4%; HzR, 0.91; 95% CI, 0.74 to 1.13; P = .39). Although remission was not improved (88% v. 85%; P = .15), posthoc analyses found relapse risk (RR) was significantly reduced among GO recipients overall (3 years: 32.8% v. 41.3%; HzR, 0.73; 95% CI, 0.58 to 0.91; P = .006). Despite an increased postremission toxic mortality (3 years: 6.6% v. 4.1%; HzR, 1.69; 95% CI, 0.93 to 3.08; P = .09), disease-free survival was better among GO recipients (3 years: 60.6% v. 54.7%; HzR, 0.82; 95% CI, 0.67 to 1.02; P = .07)., Conclusion: GO added to chemotherapy improved EFS through a reduction in RR for children and adolescents with AML.

The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median age and race were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM., (© 2014 by The American Society of Hematology.)

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.

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.

Objectives: Caring for a child with a cancer can result in significant financial strain on families, which in turn can affect parental emotional, physical, and social health. We explored the supportive factors and resources that helped single parents of children with cancer throughout the caregiving process., Methods: Using a constructivist grounded theory approach, we recruited 29 single parents of children with cancer that were at least 6 months postdiagnosis and 2 hospital social workers across 4 Canadian pediatric oncology centers., Results: Many parents had knowledge of, accessed, and received support from family, friends, community (eg, teachers, religious organizations) and cancer organizations and government programs. Nonetheless, they reported a number of unmet needs., Conclusions: Participants reported their need for more social-emotional, practical, and financial support to assist them with their caregiving duties. We recommend that hospitals provide education to describe (a) supports available to families and (b) parental caregiver needs to families' support networks. Further research is needed to identify limitations of the current public benefit schemes for caregivers.

Background: Infection continues to be a major problem for children with acute myeloid leukemia (AML). Objectives were to identify factors associated with infection, sepsis, and infectious deaths in children with newly diagnosed AML., Methods: We conducted a retrospective, population-based cohort study that included children ≤ 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease, or death (whichever occurred first). Consistent trained research associates abstracted all information from each site., Results: 341 patients were included. Median age was 7.1 years (interquartile range [IQR], 2.0-13.5) and 29 (8.5%) had Down syndrome. In sum, 26 (7.6%) experienced death as a first event. There were 1277 courses of chemotherapy administered in which sterile site microbiologically documented infection occurred in 313 courses (24.5%). Sepsis and infectious death occurred in 97 (7.6%) and 16 (1.3%) courses, respectively. The median days of corticosteroid administration was 2 per course (IQR, 0-6). In multiple regression analysis, duration of corticosteroid exposure was significantly associated with more microbiologically documented sterile site infection, bacteremia, fungal infection, and sepsis. The only factor significantly associated with infectious death was days of corticosteroid exposure (odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P = .001)., Conclusions: In pediatric AML, infection, sepsis, and infectious death were associated with duration of corticosteroid exposure. Corticosteroids should be avoided when possible for this population.

Purpose: Research looking at the health of parents of children with cancer typically uses outcome measures focused on symptoms of anxiety, depression, or post-traumatic stress. Our team builds on this literature to provide a more comprehensive understanding of the health impact of caregiving., Methods: Interviews were conducted with 79 Canadian parents of children with cancer at least 6 months post-diagnosis. Line-by-line coding was used to establish categories and themes. Constant comparison was used to examine relationships within and across codes and categories. Interviewing continued until no new themes emerged., Results: Parents described health concerns as including sleep disturbance, daytime fatigue, anxiety, depression, social isolation, and changes in social roles. Parents described the positive impacts of caregiving as including gaining a greater appreciation for child and family and developing compassion, empathy, patience, inner strength, and new perspectives on life., Conclusion: Parents of children with cancer can experience a range of health problems due to the emotional impact of a cancer diagnosis and the intensive and often prolonged nature of treatment and aftercare. Given the central role parents play as caregivers, it is crucial to understand the health impact of caregiving so that supportive interventions can be implemented as necessary.

Objective: Traditionally, measures have been developed using classical test theory (CTT). This study examines the psychometrics of the PedsQL 4.0 Generic Core Scales (parent report) using a modern psychometric approach (i.e., Rasch analysis) to determine if further insight regarding the behavior of the measure can be gained using a modern approach., Study Design and Setting: Data from a Canadian study of 376 parents of children aged 2-17 years on active cancer treatment were analyzed using Rumm2030 software (RUMM Laboratory, Australia)., Results: Overall data did not fit the Rasch model and indicated important limitations in the PedsQL including disordered item thresholds, local dependency, and poor targeting. The internal consistency was higher using CTT (Cronbach's α=0.93) than Rasch (Person Separation Index=0.78). Rasch item curves showed that respondents did not discriminate between the five-point response categories and a three-point scale was easier to discriminate., Conclusions: The PedsQL is the most widely used generic measure of health-related quality of life in pediatrics. The use of Rasch allows detailed item-level evaluation and assists in identifying limitations of measures that could then be further explored. Studies are needed in other populations to better understand the behavior of the PedsQL from a modern psychometric perspective., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Language is an important aspect of health literacy and plays a vital role in families' ability to access and use health information and resources. Our study explored the role of communication and language in the healthcare experiences of immigrant parents of children with cancer living in Canada., Procedure: We used a grounded theory approach. Chinese and South Asian parents of children 6 months post-diagnosis were recruited from six Canadian pediatric oncology centers. Semi-structured interviews were conducted in Cantonese, Mandarin, Hindi, Punjabi, Urdu, or English. Questions relevant to communication included: how parents navigated the healthcare system; nature of interpreter services and translated materials; and suggestions about how to improve services. Analysis involved line-by-line, focused and theoretical coding, and constant comparison., Results: Thirty-one (62%) parents reported no difficulty communicating with healthcare providers in English, while 13 (26%) parents struggled with English, and six (12%) parents could not communicate in English. Communication challenges influenced parents' role in caring for their child and made it difficult to learn complex medical terminology. Interpreting services were sometimes inadequate or not accessible. Parents occasionally missed out on services and resources, reported limited availability of linguistically and culturally appropriate information, and experienced a lack of social integration in the healthcare process., Conclusion: Language ability played an essential role in parents' healthcare experiences for pragmatic and social purposes. Language challenges can heighten systemic and socio-cultural barriers to accessing health information and resources. The provision of enhanced culturally and linguistically sensitive services may support immigrant families in their caregiving role., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: Research indicates complementary and alternative medicine (CAM) use among children with cancer is common and widespread. CAM use, particularly traditional Chinese medicine (TCM), is prevalent in the country of origin of Chinese immigrant families, yet little is known about its use after immigrating to Canada. This paper describes 25 Chinese immigrant parents' perception about the use of CAM in their child with cancer in Canada., Methods: This qualitative grounded theory study is part of a larger study of the caregiving experiences of first generation Chinese and South Asian parents of children with cancer. Chinese parents of children at least 6 months post-diagnosis were recruited from four Canadian pediatric oncology centers. Interviews were conducted in English, Cantonese, or Mandarin and transcribed into English. Analysis involved coding and the use of the constant comparison method to identify important themes., Results: In discussing their caregiving experiences, CAM emerged as an important theme. The following sub-themes were identified: (1) trust in conventional medicine to cure cancer; (2) use of dietary modifications and restrictions; (3) extent of communication with healthcare providers about TCM use; and (4) limited availability of culturally relevant information., Conclusions: While Chinese immigrant parents in this study placed their trust in conventional medicine to treat their child, the use of food as therapy is part of their daily cultural practice. To ensure safe cancer treatment and more culturally sensitive care, it is essential for health providers to offer reliable information and encourage open discussions about CAM use with Chinese immigrant parents.

Background: It is currently unknown how the intensive and often prolonged treatment of childhood cancer impacts on the lives of single parents. Our aims were to determine whether single parents differ from parents from two-parent families in terms of caregiver demand (the time and effort involved in caregiving), and health-related quality of life (HRQL)., Procedures: Forty single parents and 275 parents from two-parent families were recruited between November 2004 and February 2007 from five pediatric oncology centers in Canada. Parents were asked to complete a questionnaire booklet composed of items and scales to measure caregiver demand and HRQL (SF-36). The booklet also measured the following constructs: background and context factors, child factors, caregiving strain, intrapsychic factors, and coping factors., Results: Single parents did not differ from parents from two-parent families in caregiving demand and physical and psychosocial HRQL. Compared with Canadian population norms for the SF-36, both groups reported clinically important differences (i.e., worse health) in psychosocial HRQL (effect size ≥ -2.00), while scores for physical HRQL were within one standard deviation of population norms., Conclusion: Our findings suggest that the impact of caregiving on single parents, in terms of caregiving demand and HRQL is similar to that of parents from two-parent families., (Copyright © 2011 Wiley Periodicals, Inc.)

The purpose of this study is to describe cultural beliefs and coping strategies related to dealing with childhood cancer identified through a qualitative study of the caregiving experiences of first-generation South Asian immigrant parents of children with cancer. A constructivist grounded theory approach was employed. Families with a child at least 6 months postdiagnosis were recruited from 5 Canadian pediatric oncology centers. In-depth semistructured interviews were conducted in English, Hindi, Punjabi, or Urdu with a sample of 25 South Asian parents. Analysis of interviews involved line-by-line coding and using the constant comparison method. The following 2 central themes related to culture and coping emerged: (a) cultural beliefs about childhood cancer being incurable, rare, unspeakable, and understood through religion and (b) parental coping strategies included gaining information about the child's cancer, practicing religious rituals and prayers, trusting the health care professionals, and obtaining mutual support from other South Asian parents. These cultural beliefs and coping strategies have important implications for health care providers to understand the variations in the perceptions of childhood cancer and coping in order to implement culturally sensitive health care services.

A comprehensive evaluation of the psychometric properties of Care of My Child With Cancer (CMCC) was performed in a sample of 411 parents of children undergoing treatment of cancer at five Canadian pediatric oncology centers. Psychometric tests used to assess data quality, targeting, reliability, and construct validity demonstrated that the CMCC is a scientific sound measure. The CMCC will be helpful for assessing increasing parental responsibility for caregiving tasks associated with cancer care., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To compare the health-related quality of life (QOL) of parents of children who are undergoing treatment for cancer with that of Canadian population norms and to identify important parent and child predictors of parental QOL., Patients and Methods: A total of 411 respondents of 513 eligible parents were recruited from five pediatric oncology centers in Canada between November 2004 and February 2007. Parents were asked to complete a questionnaire booklet that included a measure of adult QOL (SF-36), a measure of child health status (functional status IIR), and questions to assess health-promoting self-care actions (eg, sleep, diet, and exercise habits) and characteristics of the child with cancer (eg, relapse status, time since diagnosis, prognosis, treatment intensity)., Results: Compared with population norms, parents of children with cancer reported poorer physical and psychosocial QOL in all psychosocial domains (effect sizes range, -0.71 to -1.58) and in most physical health domains (effect sizes range, -0.08 to -0.63). Parent characteristics associated with better parental QOL included better eating, exercise and sleep habits, younger age, and higher income. Child characteristics associated with better parental QOL included better child health status (functional status IIR scores), lower treatment intensity, and longer time since diagnosis., Conclusion: Parents of children with cancer report poorer QOL compared with population norms. Interventions directed at parents should be included as part of the treatment plan for a child with cancer. Modifiable variables associated with poorer parental QOL, such as sleep quality and diet and exercise habits, indicate those parents most likely to experience poor QOL and may be potential areas for intervention.

Background: Carboplatin-based regimens have demonstrated activity in pediatric patients with low-grade glioma (LGG). However, carboplatin hypersensitivity reaction (Cb HSR) represents a common and limiting factor for the continuation of therapy., Methods: The objectives of this study were to describe the prevalence, characteristics, and management of Cb HSR and to detail their impact on outcome. The authors conducted a comprehensive, national, retrospective review of children who were diagnosed with LGG between 1985 and 2004 and received treatment with carboplatin., Results: One hundred five patients from 10 Canadian centers were included. The median patient age at diagnosis was 3.5 years (range, 0.3-16.8 years), and 33 patients (31.4%) had neurofibromatosis type 1. Carboplatin was administered monthly in 46 children and weekly in 59 children. Forty-four patients (41.9%) developed Cb HSR after a median of 10.5 infusions (range, 3-39 infusions). Cb HSR occurred significantly earlier among children on the weekly schedule (4.4 months vs 9.1 months; P = .02). The first allergic reaction was grade I or II in 36 patients (82%). The cumulative incidence of Cb HSR increased with the number of infusions, and there was no evidence of a plateau. The only predictive factor was being a girl rather than a boy (P = .02). Thirty-four of 44 patients with Cb HSR were re-exposed to carboplatin, and 24 of 34 patients (70.5%) had recurrent Cb HSR. A desensitization approach did not provide any advantage compared with premedication alone for altering Cb HSR. The median number of additional Cb infusions delivered was 4 (range, 0.5-34 infusions). The effect of Cb HSR on the 5-year progression-free survival rate was not statistically significant (P = .1)., Conclusions: Forty-two percent of children with LGG who received carboplatin regimens experienced Cb HSR. Most rechallenged children had recurrent Cb HSR despite Cb HSR-altering regimens. Cb HSR did not have an impact on progression-free survival., (Cancer 2008. (c) 2007 American Cancer Society.)

Introduction: Supratentorial primitive neuroectodermal tumors (SPNET) are rare tumors accounting for only 2.5% of childhood brain tumors. The purpose of this study was to describe the range of treatment regimens used to treat pediatric SPNET in Canada and to identify prognostic factors for overall survival in this population., Methods: This study was a retrospective clinical analysis of SPNET patients treated over the last 10 years in Canada. A questionnaire was developed and distributed to all institutions in Canada who treat pediatric patients. Data were collected for patients <19 years of age who were diagnosed and treated for SPNET between 1995 and 2005., Results: Data were obtained for 48 eligible patients. The stages of patients for whom complete data were provided were 80, 3, and 16% for metastatic stage M0, M1, and M2/3, respectively. The best responses to therapy included complete response in 44%, partial response in 8%, still on therapy in 2%, progressive disease in 31%, toxic death in 2%, and no therapy given in 12%. The 4-year survival was 37.7 +/- 7.6%. The factors associated with an increase in survival were the use of radiation therapy and chemotherapy, and age >2 years. Overall survival was not affected by metastatic disease at diagnosis, tumor site, or degree of initial resection., Conclusions: Survival is poor in SPNET patients but highest in those who received chemotherapy and radiation therapy. Further studies are needed to improve the survival of these patients.

We identified all children enrolled in the Intergroup Rhabdomyosarcoma Study Group-IV with neurofibromatosis type I (NF1) and rhabdomyosarcoma. Among 1025 eligible patients, 5 (0.5 %) had NF1. Three children had relapses, two of whom died of progressive disease. Patients with NF1 and rhabdomyosarcoma should be treated with intensive contemporary therapy protocols.

Background: Neuroblastoma, an embryonic tumor, is the second most common pediatric tumor and is the most prevalent extracranial solid tumor in children. Results of previous studies have suggested that maternal vitamin intake may decrease the risk of several childhood cancers. In January 1997, Canada began fortifying flour with folic acid for the prevention of neural tube defects. The effect of folic acid fortification on the rate of neuroblastoma in offspring is not known., Methods: We investigated the rates of neuroblastoma (<1 year), acute lymphoblastic leukemia, and hepatoblastoma registered by the Pediatric Oncology Group of Ontario, which captures 95% of all pediatric cancers in Ontario, before and after the introduction of folate fortification., Results: An interventional time series analysis showed that the incidence of neuroblastoma declined from 1.57 cases per 10,000 births before to 0.62 case per 10,000 births after folic acid fortification (P <.0001). The crude incidence rate ratio (0.40; 95% confidence interval, 0.25-0.64) remained significant after adjustment for both age and disease stage at diagnosis (adjusted incidence rate ratio, 0.38; 95% confidence interval, 0.23-0.62). In contrast, there was no significant change in the rate of infant acute lymphoblastic leukemia (incidence rate ratio, 0.97; 95% confidence interval, 0.41-2.27) or hepatoblastoma (incidence rate ratio, 0.81; 95% confidence interval, 0.35-1.89)., Conclusions: Folic acid fortification was associated with a 60% reduction in neuroblastoma but was not associated with any change in the rate of infant acute lymphoblastic leukemia or hepatoblastoma. Further investigation is needed into the role of metabolism in the formation and prevention of neuroblastoma and other embryonically determined cancers.