Guideline for the management of Clostridioides difficile infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.

Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI.

Guideline for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients: 2023 update.

Objective was to update a clinical practice guideline (CPG) for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients. We reconvened a multi-disciplinary and multi-national panel. While the previous 2018 CPG evaluated adult and pediatric randomized controlled trials (RCTs) to manage fatigue, this 2023 update revised previous recommendations based only on pediatric RCTs. Twenty RCTs were included in the updated systematic review. Physical activity significantly reduced fatigue (standardized mean difference -0.44, 95% confidence interval -0.64 to -0.24; n = 8 RCTs). Using the 2018 recommendations as a basis, the panel continued to make strong recommendations to use physical activity, and to offer relaxation, mindfulness or both, to manage fatigue in pediatric patients. Cognitive or cognitive behavioral therapies may be offered. Pharmacological approaches should not be routinely used. The panel made a new good practice statement to routinely assess for fatigue, ideally using a validated scale.

IPO11 regulates the nuclear import of BZW1/2 and is necessary for AML cells and stem cells.

AML cells are arranged in a hierarchy with stem/progenitor cells giving rise to more differentiated bulk cells. Despite the importance of stem/progenitors in the pathogenesis of AML, the determinants of the AML stem/progenitor state are not fully understood. Through a comparison of genes that are significant for growth and viability of AML cells by way of a CRISPR screen, with genes that are differentially expressed in leukemia stem cells (LSC), we identified importin 11 (IPO11) as a novel target in AML. Importin 11 (IPO11) is a member of the importin ß family of proteins that mediate transport of proteins across the nuclear membrane. In AML, knockdown of IPO11 decreased growth, reduced engraftment potential of LSC, and induced differentiation. Mechanistically, we identified the transcription factors BZW1 and BZW2 as novel cargo of IPO11. We further show that BZW1/2 mediate a transcriptional signature that promotes stemness and survival of LSC. Thus, we demonstrate for the first time how specific cytoplasmic-nuclear regulation supports stem-like transcriptional signature in relapsed AML.

Clinical Practice Guideline for Systemic Antifungal Prophylaxis in Pediatric Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients.

PURPOSE: To develop a clinical practice guideline for systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplantation (HSCT) recipients. METHODS: Recommendations were developed by an international multidisciplinary panel that included a patient advocate. We conducted a systematic review of systemic antifungal prophylaxis in children and adults with cancer and HSCT recipients. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to make strong or weak recommendations and to classify level of evidence as high, moderate, low, or very low. The panel considered directness of the data to pediatric patients. RESULTS: There were 68 randomized trials included in the systematic review, of which 6 (9%) were conducted in a solely pediatric population. Strong recommendations were made to administer systemic antifungal prophylaxis to children and adolescents receiving treatment of acute myeloid leukemia, to those undergoing allogeneic HSCT pre-engraftment, and to those receiving systemic immunosuppression for graft-versus-host disease treatment. A strong recommendation was made to administer a mold-active agent with an echinocandin or a mold-active azole when systemic antifungal prophylaxis is warranted. For children younger than 13 years of age, an echinocandin, voriconazole, or itraconazole is suggested. Posaconazole may also be used in those age 13 years or older. A strong recommendation against routine administration of amphotericin as systemic antifungal prophylaxis was made. CONCLUSION: We developed a clinical practice guideline for systemic antifungal prophylaxis administration in pediatric patients with cancer and HSCT recipients. Implementation and assessment of guideline-concordant rates and impacts are important future steps.

Longitudinal evaluation of Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK), a symptom screening and management application.

BACKGROUND: Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK) is a web application focused on improving symptom control. It enables pediatric cancer and hematopoietic stem cell transplant (HSCT) patients to self-report and track symptoms, and allows healthcare professionals to access guidelines for symptom management. Objective was to determine the feasibility of longitudinal collection of symptom data. METHODS: In this longitudinal, single-armed feasibility study, respondents were children 8-18 years of age with cancer or pediatric HSCT recipients. Participants completed symptom reporting daily for 5 days. Cognitive interviews were conducted on day 5. Quantitative evaluation included SPARK ease of use and understandability of SPARK reports. Qualitative feedback on facilitators and barriers to daily symptom screening was solicited. Feasibility was defined as ≥75% of participants completing symptom screening on at least 60% of on-study days during the five-day study. RESULTS: Among the 30 children enrolled, the median number of days SSPedi was completed at least once was 5 (range 3 to 5). Overall, 28/29 (96.6%) thought completing symptom screening using SPARK was easy or very easy. All participants understood SPARK symptom reports. Severe symptoms was the most common barrier to daily reporting while an alarm reminder system was the most commonly identified facilitator. CONCLUSIONS: Daily completion of symptom screening using SPARK over 5 days was feasible in children aged 8 to 18 years with cancer and pediatric HSCT recipients. SPARK is now appropriate for use in randomized trials to evaluate the effect of symptom screening and symptom feedback.

Symptom documentation and intervention provision for symptom control in children receiving cancer treatments.

BACKGROUND: Objectives were to describe the proportion of bothersome symptoms self-reported using the Symptom Screening in Pediatrics Tool (SSPedi) documented in the medical records and associated with an intervention. METHODS: Eligible respondents were inpatients aged 8-18 years receiving cancer treatments and expected to be in hospital or clinic three days later. Children self-reported symptom bother using SSPedi. We evaluated symptom documentation and interventions in the medical records proximal to SSPedi administration. RESULTS: There were 168 children included. Symptoms rated as at least 'a lot' bother were documented in the medical record less than 60% of the time for 12 of 15 symptoms. Of these symptoms, the most infrequently documented symptoms were problems with thinking or remembering things (0%), changes in how your body or face look (4.8%), changes in taste (7.7%) and tingly or numb hands or feet (11.1%). Intervention provision for symptoms rated as 'a lot' bother occurred less than 60% of the time for 10 of 15 symptoms. Of these symptoms, the most infrequently treated were thinking or remembering things (0%), changes in how your body or face look (0%), tingly or numb hands or feet (0%), changes in taste (0%), diarrhoea (0%) and feeling tired (1.6%). CONCLUSIONS: Documentation of symptoms and intervention provision were generally infrequent. Symptoms that were almost never documented or treated included problems with cognition, body image, taste changes and peripheral neuropathy. Future efforts should incorporate symptom screening into routine care and facilitate symptom management by improving access to evidence-based clinical practice guidelines.

Severity, change over time, and risk factors of anxiety in children with cancer depend on anxiety instrument used.

OBJECTIVE: The primary objective was to describe severity of anxiety among children and adolescents receiving chemotherapy for cancer or undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives were to describe how anxiety changes over time and determine factors associated with anxiety. METHODS: Participants were aged 8 to 18 and either receiving chemotherapy for cancer or undergoing HSCT for any indication. Respondents self-reported three anxiety measurement instruments at chemotherapy cycle or HSCT conditioning start and 3 weeks later. RESULTS: The proportion of participants with severe anxiety ranged from 10/77 (13.0%) to 22/77 (28.6%) depending on instrument used. Change over time also varied across instruments, with significant improvement observed with PedsQL (procedural) (P = 0.037) and PROMIS (P = 0.013). Factors associated with anxiety similarly varied by instrument. Older age was associated with more anxiety on the PedsQL (worry) (P = 0.036), and higher household income was associated with less anxiety on the MASC-10 (P = 0.028). CONCLUSIONS: While we found that a small proportion of patients met or exceeded thresholds for severe anxiety, we also noted that severity, change over time, and predictors of anxiety varied depending on instrument used. Future research should ensure that selected instruments measure the construct of interest and describe how anxiety is conceptualized in the study.

Initial development of Supportive care Assessment, Prioritization and Recommendations for Kids (SPARK), a symptom screening and management application.

BACKGROUND: We developed Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK), a web-based application designed to facilitate symptom screening by children receiving cancer treatments and access to supportive care clinical practice guidelines primarily by healthcare providers. The objective was to describe the initial development and evaluation of SPARK from the perspective of children. IMPLEMENTATION: Development and evaluation occurred in three phases: (1) low fidelity focused on functionality, (2) design focused on "look and feel" and (3) high fidelity confirmed functionality and design. Cognitive interviews were conducted with children receiving cancer treatments 8-18 years of age. Evaluation occurred after every five interviews and changes were guided by a Review Panel. Quantitative evaluation included SPARK ease of use and understandability of SPARK reports. RESULTS: The number of children included by phase were: low fidelity (n = 30), design (n = 30) and high fidelity (n = 30). Across phases, the median age was 13.2 (range 8.5 to 18.4) years. During low-fidelity and design phases, iterative refinements to SPARK improved website navigation, usability and likability from the perspective of children and established symptom report design. Among the last 10 children enrolled to high-fidelity testing, all (100%) understood how to complete symptom screening, access reports and interpret reports. Among these 10 respondents, all (100%) found SPARK easy to use and 9 (90%) found SPARK reports were easy to understand. CONCLUSIONS: SPARK is a web-based application which is usable and understandable, and it is now appropriate to use for research. Future efforts will focus on clinical implementation of SPARK.

Management of fatigue in children and adolescents with cancer and in paediatric recipients of haemopoietic stem-cell transplants: a clinical practice guideline.

Fatigue is a prevalent and distressing symptom in children and adolescents with cancer and in those who have undergone haemopoietic stem-cell transplantation. A multidisciplinary and multinational group of experts in paediatric oncology and fatigue, together with patient advocates, developed a clinical practice guideline for management of fatigue on the basis of systematic reviews that included six paediatric and 456 adult randomised studies. We used the Grading of Recommendations Assessment, Development and Evaluation approach to generate recommendations, and made strong recommendations, supported by evidence of moderate quality, for use of physical activity, relaxation, and mindfulness to reduce fatigue. When these approaches are unsuccessful or not feasible, cognitive or cognitive behavioural therapies may be offered (weak recommendation supported by evidence of moderate quality). Maturity and cognitive ability of individual patients will affect the feasibility of interventions. Systemic pharmacological approaches should not be routinely used to manage fatigue in children. Apart from identification of optimal approaches to implement recommended interventions in clinical practice, future research should also address knowledge gaps, including establishment of minimum age thresholds for interventions and inclusion of paediatric patients in randomised trials of fatigue management.

Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis of randomized trials.

PURPOSE: Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients. METHODS: We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients. RESULTS: There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference -0.49, 95% confidence interval -0.60 to -0.37; P < 0.00001). Aerobic, neuromotor, resistance and combination exercises were all effective in reducing fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue. CONCLUSIONS: Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority.

Mind and body practices for fatigue reduction in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis.

PURPOSE: To determine whether non-physical activity mind and body practices reduce the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients compared to control interventions. METHODS: We included randomized trials which compared non-physical activity mind and body practices compared with control interventions for the management of fatigue in cancer and HSCT patients. RESULTS: Among 55 trials (4975 patients), interventions were acupuncture or acupressure (n=12), mindfulness (n=11), relaxation techniques (n=10), massage (n=6), energy therapy (n=5), energizing yogic breathing (n=3) and others (n=8). When combined, all interventions significantly reduced fatigue severity compared to all controls (standardized mean difference -0.51, 95% confidence interval -0.73 to -0.29). More specifically, mindfulness and relaxation significantly reduced fatigue severity. CONCLUSIONS: Mindfulness and relaxation were effective at reducing fatigue severity in patients with cancer and HSCT recipients. Future studies should evaluate how to translate these findings into clinical practice across different patient groups.