The evolution of nutritional care in children and young people with acute lymphoblastic leukaemia: a narrative review.

BACKGROUND: Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy in the world. Advances in treatment protocols have resulted in survival rates of >80% in most high-income countries (HIC); however, children and young people (CYP) with ALL continue to face significant nutrition-related challenges during treatment. METHODS: This narrative review outlines the changing landscape of treatment and survivorship for CYP with ALL and the advances in nutrition knowledge that call for changes to clinical nutrition practice. RESULTS: The incidence of ALL has remained stable in HIC; however, there have been significant advances in survival over the past 30 years. Overweight and obesity are increasingly prevalent in CYP with ALL at diagnosis, during treatment and in survivorship. Coupled with poor diet quality, high-energy and saturated fat intakes, altered eating behaviours and inactivity, this necessitates the need for a shift in nutrition intervention. Undernutrition remains a concern for CYP with high-risk treatment protocols where oral or enteral nutrition support remains a cornerstone of maintaining nutrition status. CONCLUSIONS: With improved treatment protocols and high survival rates, a shift to focusing on diet quality, prevention of excessive weight gain and obesity during treatment and survivorship is necessary.

National advisory panels for childhood cancer in the United Kingdom: An evaluation of current practice and a best practice statement for the future.

BACKGROUND: National advisory panels (NAPs) have been established for the care of children and young people (CYP) with cancer in the United Kingdom since 2011, with an increase in panel number in recent years. Their practice has not previously been reviewed; therefore, we sought to evaluate the role, practice and impact of six selected NAPs offering expertise in ependymoma, histiocytosis, leukaemia, neuroblastoma, renal tumours and sarcoma. PROCEDURE: This service evaluation used mixed methodology, including review of NAP documentation, semi-structured interviews with the NAP chairs and an analysis of the cases referred for discussion. RESULTS: Total 1110 referrals were analysed. Results demonstrated the significant scope and amount of work undertaken by the NAPs, largely testament to the commitment of the panel members. Specific roles fulfilled have been highlighted, and NAP recommendations have been shown to influence clinical decision-making and be implemented in the majority of cases. Despite widespread good practice, areas to address have been identified; these include clarity regarding NAP membership, consistency in recommendations, the consideration of holistic information to promote personalised management and the exploration of wider multidisciplinary team roles. CONCLUSIONS: In the context of increasing demand and the escalating number of NAPs, it is timely to consider how service improvement can be facilitated. Best practice guidelines have been formulated as a product of this study, to promote a sustainable and effective model for NAPs. Review and benchmarking national panel performance against these guidelines will drive high standards of care going forward and they should be embedded as standard practice.

Global caregiver concerns of SARS-CoV-2 vaccination in children with cancer: a cross-sectional mixed-methods study.

The objective of this study was to understand global caregiver concerns about SARS-CoV-2 vaccination for children with cancer and to provide healthcare providers with guidance to support parental decision-making. A co-designed cross-sectional mixed-methods survey was distributed to primary caregivers of children with cancer globally between April and May 2021 via several media. Caregivers were asked to rate the importance of vaccine-related questions and the median scores were ranked. Principal Component Analysis was conducted to identify underlying dimensions of caregiver concerns by World Bank income groups. Content analysis of free-text responses was conducted and triangulated with the quantitative findings. 627 caregivers from 22 countries responded to the survey with 5.3% (n = 67) responses from low-and-middle-income countries (LMIC). 184 caregivers (29%) provided free-text responses. Side effects and vaccine safety were caregivers' primary concerns in all countries. Questions related to logistics were of concern for caregivers in LMIC. A small minority of caregivers (n = 17) did not consider the survey questions important; free-text analysis identified these parents as vaccine hesitant, some of them quoting safety and side effects as main reasons for hesitancy. Healthcare providers and other community organizations globally need to provide tailored information about vaccine safety and effectiveness in pediatric oncology settings. Importantly, continued efforts are imperative to reduce global inequities in logistical access to vaccines, particularly in LMIC.

Answers to common questions about COVID-19 vaccines in children with cancer.

BACKGROUND: The SARS-CoV-2 outbreak in 2020 evolved into a global pandemic, and COVID-19 vaccines became rapidly available, including for pediatric patients. However, questions emerged that challenged vaccine acceptance and use. We aimed to answer these questions and give recommendations applicable for use in pediatric patients with cancer by healthcare professionals and the public. METHODS: A 12-member global COVID-19 Vaccine in Pediatric Oncology Working Group made up of physicians and nurses from all world regions met weekly from March to July 2021. We used a modified Delphi method to select the top questions. The Working Group, in four-member subgroups, answered assigned questions by providing brief recommendations, followed by a discussion of the rationale for each answer. All Working Group members voted on each recommendation using a scale of 1 to 10, 10 being complete agreement. A "pass" recommendation corresponded to an agreement ≥7.5. RESULTS: We selected 15 questions from 173 suggested questions. Based on existing published information, we generated answers for each question as recommendations. The overall average agreement for the 24 recommendations was 9.5 (95% CI 9.4-9.6). CONCLUSION: Top COVID-19 vaccine-related questions could be answered using available information. Reports on COVID-19 vaccination and related topics have been published at record speed, aided by available technology and the priority imposed by the pandemic; however, all efforts were made to incorporate emerging information throughout our project. Recommendations will be periodically updated on a dedicated website.

Implementation of multidisciplinary reflective rounds within a children's hospital before and during the COVID-19 pandemic.

AIM: Regular reflective practice within a large group setting has been shown to reduce levels of burnout in healthcare professionals. We describe how regular reflective rounds were designed and implemented within an existing educational program at a UK children's hospital and report on the feedback received from participants. METHODS: Eight face-to-face reflective rounds took place in Southampton Children's Hospital, UK, from September 2017 to February 2020 with a further virtual round in July 2020 during the COVID-19 pandemic. Each round was facilitated by a clinical psychologist and consultant. For each round, up to three volunteer panellists from different staff groups were invited to share their personal experiences on a pre-selected subject to the large group. The group would then contribute to the discussion by offering their own reflections. Feedback forms were distributed to attendees and collated. RESULTS: Eight rounds were held with mean attendance of 32 (range 19-47). Across the eight rounds, the total attendance was 256 staff members. The virtual round had 20 participants. Feedback was received from 202 participants. The majority (98%) would recommend the rounds to colleagues with 64 participants (32%) rating the rounds as 'exceptional' and 91 (45%) as 'excellent'. The virtual round received similar positive feedback. CONCLUSION: Large group reflective practice can be implemented within an existing regular educational program. Rounds have been well received by participants and are likely to be of relevance and value to other healthcare groups. The rounds can also be delivered effectively virtually, which may increase participation.

Thirteen-Valent Pneumococcal Conjugate Vaccine in Children With Acute Lymphoblastic Leukemia: Protective Immunity Can Be Achieved on Completion of Treatment.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) are at increased risk of developing invasive pneumococcal disease. This study describes the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) during and after chemotherapy. METHODS: Children with ALL were allocated to study groups and received a single dose of PCV13: group 1, maintenance chemotherapy; group 2, end of chemotherapy; group 3, 6 months after chemotherapy. A protective vaccine response was defined as at least 10 of 12 serotypes (or >83% of serotypes with data) achieving postvaccination serotype-specific immunoglobulin G ≥0.35 µg/mL and ≥4-fold rise, compared to prevaccination at 1 and 12 months. RESULTS: One hundred eighteen children were recruited. Only 12.8% (5/39; 95% confidence interval [CI], 4.3%-27.4%) of patients vaccinated during maintenance (group 1) achieved a protective response at 1 month postvaccination and none had a protective response at 12 months. For group 2 patients, 59.5% (22/37; 95% CI, 42.1%-75.3%) achieved a response at 1 month and 37.9% (11/29; 95% CI, 20.7%-57.7%) maintained immunity at 12 months. For group 3 patients, 56.8% (21/37; 95% CI, 39.5%-72.9%) achieved a protective response at 1 month and 43.3% (13/30; 95% CI, 25.5%-62.6%) maintained immunity at 12 months. CONCLUSIONS: This study demonstrated that the earliest time point at which protective immunity can be achieved in children with ALL is on completion of chemotherapy. This is earlier than current recommendations and may improve protection during a period when children are most susceptible to infection. CLINICAL TRIALS REGISTRATION: EudraCT 2009-011587-11.

Patient perspectives on a national multidisciplinary team meeting for a rare cancer.

Multidisciplinary team meetings (MDTM) provide a regular forum for cancer teams to convene and discuss the diagnostic and treatment aspects of patient care. For some rare cancers, MDTMs may also occur at national level to pool expertise and to ensure more consistent decision-making. One such national MDTM exists in the UK for patients with a diagnosis of Ewing's sarcoma of the bone-the National Ewing's MDT (NEMDT). This study explored the patient perspective of this rare cancer national MDTM using focus group and survey methodology. Study participants used their experience to provide several recommendations: that their views should always inform the decision-making process, these views should be presented by someone who has met them such as a specialist nurse, MDT recommendations should be provided to them in plain English, and tools to improve patient choice and enhance communication should be implemented. These patient-centred recommendations will be used to improve the NEMDT but may be valid to inform quality improvement processes for other similar national panels.

Vocal Cord Palsy in Children With Cancer: A 10-Year Analysis of UK Pediatric Intensive Care Admissions.

Vocal cord palsy (VCP) is a rare but potentially life-threatening complication in children with cancer. This study reviews UK Intensive Care admissions for children with cancer and VCP using data obtained from the Pediatric Intensive Care Audit Network (PICANet) database. 26 children with cancer and VCP were admitted to intensive care from 2002 to 2012. The majority of admissions (23/26) required respiratory intervention (17 invasive ventilation, 8 noninvasive ventilation, and 5 tracheostomy). VCP should be considered early in children with cancer who present with signs of upper airway obstruction, especially in those receiving vinca-alkaloids as VCP is likely to be reversible.

Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003.

Although infection is the major cause of treatment-related mortality (TRM) in childhood acute lymphoblastic leukemia, factors associated with infection-related mortality (IRM) are poorly understood. To address this, we report an analysis of all 75 cases of IRM in the United Kingdom Childhood Acute Lymphoblastic Leukaemia Randomised Trial 2003 (UKALL 2003). The 5-year cumulative incidence of IRM was 2.4% (95% confidence interval [CI], 1.9%-3.0%), accounting for 75 (30%) of 249 trial deaths and 75 (64%) of 117 TRM deaths. Risk for IRM as a proportion of TRM was greater in induction than other phases (77% vs 56%; P = .02). Sixty-eight percent of cases were associated with bacterial infection (64% Gram-negative) and 20% with fungal infection. Down syndrome was the most significant risk factor for IRM (odds ratio [OR], 12.08; 95% CI, 6.54-22.32; P < .0001). In addition, there was a trend toward increased IRM in girls (OR, 1.63; 95% CI, 1.02-2.61; P = .04), as well as increasing treatment intensity (regimen B vs A: OR, 2.11 [95% CI, 1.24-3.60]; regimen C vs A: OR, 1.41 [95% CI, 0.76-2.62]; P = .02). Importantly, patients with Down syndrome were at significantly higher risk for IRM during maintenance (P = .048). Our results confirm Down syndrome as a major risk factor for IRM. Enhanced supportive care and prophylactic antibiotics should be considered in high-risk patient groups and during periods of increased risk. This study was registered at http://www.controlled-trials.com/ as #ISRCTN07355119.

Varicella zoster immune status in children treated for acute leukemia.

Children treated for acute leukemia are at increased risk of severe infection with varicella zoster virus (VZV). We studied the VZV sero-status of children with acute leukemia prior to starting chemotherapy and after completion of chemotherapy. VZV sero-status was assessed using time resolved fluorescence immunoassay (TRFIA) before starting treatment and 6 months after completion of treatment. Prior to starting treatment for acute leukemia, a significant proportion of children (35%) are VZV seronegative. On completion of treatment most patients maintained protective VZV antibody levels; however, 35% had reduced/loss VZV antibody to a level considered non-protective and susceptible to VZV infection.

Patient and parent perspectives on paediatric cancer multidisciplinary team working and national advisory panels in the UK: a qualitative research study.

OBJECTIVE: The concept of patient-centred care is central to the role of cancer multidisciplinary teams (MDTs) and particularly pertinent with the recent rise in number of virtual national advisory panels (NAPs) for childhood cancer in the UK. We sought to explore patient and caregiver views regarding MDT working and NAPs. METHODS: Three focus groups were undertaken between March 2019 and January 2020. RESULTS: Sixteen participants attended. All regarded MDTs and NAPs highly, while highlighting patient involvement in decision-making should not be diluted by this process. The importance of personalised consultations was stressed, acknowledging that information-sharing preferences may change with circumstance and time. Most participants felt they had not been actively involved in decisions, including those made following MDT or NAP discussions. Group suggestions to improve patient-centred care included a clinician knowing them presenting their case, referral proformas to include family-related factors and an advocate attending meetings to represent the patient/family view. CONCLUSION: Several changes have been driven forward by this work, including the modification of NAP referral proformas to include additional information. Patient and parent perspectives are now embedded into a best practice model for the NAPs to promote personalised recommendations at national level.

Global caregiver perspectives on COVID-19 immunization in childhood cancer: A qualitative study.

Introduction: SARS-CoV-2 has led to an unprecedented pandemic where vulnerable populations, such as those with childhood cancer, face increased risk of morbidity and mortality. COVID-19 vaccines are a critical intervention to control the pandemic and ensure patient safety. This study explores global caregiver's perspectives related to COVID-19 immunization in the context of pediatric cancer management. Methods: A mixed methods survey was developed based on consensus questions with iterative feedback from global medical professional and caregiver groups and distributed globally to caregivers of childhood cancer via electronic and paper routes. We present qualitative findings through inductive content analysis of caregiver free-text responses. Results: A total of 184 participants provided qualitative responses, 29.3% of total survey respondents, with a total of 271 codes applied. Codes focused on themes related to safety and effectiveness (n = 95, 35.1%), logistics (n = 69, 25.5%), statements supporting or opposing vaccination (n = 55, 20.3%), and statements discussing the limited availability of information (n = 31, 11.4%). Within the theme of safety and effectiveness, safety itself was the most commonly used code (n = 66, 24.4% of total segments and 69.5% of safety and effectiveness codes), followed by risks versus benefits (n = 18, 18.9% of safety and effectiveness codes) and efficacy (n = 11, 11.6%). Discussion: This study provides insights to guide healthcare professionals and caregiver peers in supporting families during the complex decision-making process for COVID-19 vaccination. These findings highlight the multidimensionality of concerns and considerations of caregivers of children with cancer regarding COVID-19 vaccination and suggest that certain perspectives transcend borders and cultures.

Can I go home now? The safety and efficacy of a new UK paediatric febrile neutropenia protocol for risk-stratified early discharge on oral antibiotics.

OBJECTIVE: To evaluate a new protocol of risk stratification and early discharge for children with febrile neutropenia (FN). DESIGN: Prospective service evaluation from 17 April 2020 to 16 April 2021. SETTING: 13 specialist centres in the UK. PATIENTS: 405 children presenting with FN. INTERVENTION: All children received intravenous antibiotics at presentation. Risk stratification was determined using the Australian-UK-Swiss (AUS) rule and eligibility for homecare assessed using criteria including disease, chemotherapy, presenting features and social factors. Those eligible for homecare could be discharged on oral antibiotics after a period of observation proportional to their risk group. MAIN OUTCOME MEASURES: Median duration of admission and of intravenous antibiotics, and percentage of patients with positive blood cultures, significant infection, readmission within 7 days of initial presentation, intensive care unit (ICU) admission, death from infection and death from other causes. RESULTS: 13 centres contributed 729 initial presentations of 405 patients. AUS rule scores were positively correlated with positive blood cultures, significant infection, ICU admission and death. 20% of children were eligible for homecare with oral antibiotics, of which 55% were low risk (AUS 0-1). 46% low-risk homecare eligible patients were discharged by 24 hours vs 2% homecare ineligible. Homecare readmission rates were 14% overall and 16% for low-risk cases (similar to a meta-analysis of previous studies). No child eligible for homecare was admitted to ICU or died. CONCLUSIONS: Use of the AUS rule and homecare criteria allow for safe early outpatient management of children with FN.

PEPtalk 3: oral aciclovir is equivalent to varicella zoster immunoglobulin as postexposure prophylaxis against chickenpox in children with cancer - results of a multicentre UK evaluation.

OBJECTIVE: To compare the occurrence of chickenpox in children with cancer who received varicella immunoglobulin (VZIG) or aciclovir as postexposure prophylaxis (PEP). DESIGN: Prospective multicentre service evaluation of children with cancer who received either VZIG or aciclovir as PEP following significant exposure to varicella zoster virus (VZV) over a 24-month period from May 2018. SETTING: Data were collected from 9 UK Paediatric Oncology Primary Treatment Centres. PATIENTS: Children under 16 years old with a diagnosis of cancer and/or previous haematopoietic stem cell transplant who were VZV seronegative at exposure and/or diagnosis and received PEP following significant VZV exposure. MAIN OUTCOME MEASURES: The primary outcome was the incidence of breakthrough varicella within 6 weeks of VZV exposure and treatment with PEP. RESULTS: A total of 105 eligible patients were registered with a median age of 4.9 years (range 1.1-10.5 years). Underlying diagnoses were acute leukaemia (64), solid tumours (22), Langerhans cell histiocytosis (9), central nervous system (CNS) tumours (8) and other (2). Aciclovir was received by 86 patients (81.9%), 18 received VZIG (17.1%) and 1 valaciclovir (0.9%). There were seven reported break-through VZV infections in 103 patients at follow-up (7/103, 6.8%). Clinical VZV developed in 5/84 of the aciclovir group (6.0%, 95% CI 2.0 to 13.3) and 2/18 of VZIG group (11.1%, 95% CI 1.4 to 34.7). All breakthrough infections were either mild (5/7) or moderate (2/7) in severity. CONCLUSION: Aciclovir is a safe and effective alternative to VZIG as VZV PEP in children with cancer and should be considered as standard of care.