A systematic review of early phase studies for children and young people with relapsed and refractory rhabdomyosarcoma: The REFoRMS-SR project.

Rhabdomyosarcoma is the commonest soft tissue sarcoma in children. Around one-third of children with rhabdomyosarcoma experience relapse or have refractory disease, which is associated with a poor prognosis. This systematic review of early phase studies in pediatric relapsed/refractory rhabdomyosarcoma was conducted to inform future research and provide accurate information to families and clinicians making difficult treatment choices. Nine databases and five trial registries were searched in June 2021. Early phase studies of interventions for disease control in patients under 18 years old with relapsed/refractory rhabdomyosarcoma were eligible. No language/geographic restrictions were applied. Studies conducted after 2000 were included. Survival outcomes, response rates, quality of life and adverse event data were extracted. Screening, data extraction and quality assessment (Downs and Black Checklist) were conducted by two researchers. Owing to heterogeneity in the included studies, narrative synthesis was conducted. Of 16,965 records screened, 129 published studies including over 1100 relapsed/refractory rhabdomyosarcoma patients were eligible. Most studies evaluated systemic therapies. Where reported, 70% of studies reported a median progression-free survival ≤6 months. Objective response rate was 21.6%. Adverse events were mostly hematological. One-hundred and seven trial registry records of 99 studies were also eligible, 63 of which report they are currently recruiting. Study quality was limited by poor and inconsistent reporting. Outcomes for children with relapsed/refractory rhabdomyosarcoma who enroll on early phase studies are poor. Improving reporting quality and consistency would facilitate the synthesis of early phase studies in relapsed/refractory rhabdomyosarcoma (PROSPERO registration: CRD42021266254).

A systematic review of combined surgery and brachytherapy approaches for children and young people with relapsed and refractory rhabdomyosarcoma (Local-REFoRMS).

Approximately one third of children with rhabdomyosarcoma relapse or have refractory disease. Treatment approaches include a combination of systemic therapies and local therapies, directed at tumour site(s). This review was conducted to evaluate the effectiveness and safety of the combination of surgery and brachytherapy as local therapy for treating children and young people with relapsed/refractory rhabdomyosarcoma. This review identified studies based on a previous systematic review looking at the treatments for children and young people under 18 years old with relapsed/refractory rhabdomyosarcoma. Studies conducted after 2000 were included. Survival outcomes, relapse rates, adverse events and functional outcomes were extracted. From 16,965 records identified in the baseline systematic review, 205 included the words 'AMORE' or 'brachytherapy', and were screened for eligibility in this substudy. Thirteen studies met the inclusion criteria for Local-REFoRMS, including over 55 relapsed and refractory rhabdomyosarcoma patients. Most studies were retrospective cohort studies conducted within Europe. Most patients had embryonal disease within the head and neck or bladder/prostate regions, and received local therapy for first relapse. Approximately one quarter of patients relapsed following surgery and brachytherapy, with local relapses occurring more than metastatic relapse. Adverse events and functional outcomes were infrequently reported, but related to the site of surgery and brachytherapy. Study quality was limited by inconsistent reporting and potential selection bias. Outcomes following surgery and brachytherapy for a selected group of relapsed and refractory rhabdomyosarcoma show reasonable benefits, but reporting was often unclear and based on small sample sizes.

Regional perspectives on the coordination and delivery of paediatric end-of-life care in the UK: a qualitative study.

BACKGROUND: Provision of and access to paediatric end-of-life care is inequitable, but previous research on this area has focused on perspectives of health professionals in specific settings or children with specific conditions. This qualitative study aimed to explore regional perspectives of the successes, and challenges to the equitable coordination and delivery of end-of-life care for children in the UK. The study provides an overarching perspective on the challenges of delivering and coordinating end-of-life care for children in the UK, and the impact of these on health professionals and organisations. Previous research has not highlighted the successes in the sector, such as the formal and informal coordination of care between different services and sectors. METHODS: Semi-structured interviews with Chairs of the regional Palliative Care Networks across the UK. Chairs or co-Chairs (n = 19) of 15/16 Networks were interviewed between October-December 2021. Data were analysed using thematic analysis. RESULTS: Three main themes were identified: one standalone theme ("Communication during end-of-life care"); and two overarching themes ("Getting end-of-life services and staff in the right place", with two themes: "Access to, and staffing of end-of-life care" and "Inconsistent and insufficient funding for end-of-life care services"; and "Linking up healthcare provision", with three sub-themes: "Coordination successes", "Role of the networks", and "Coordination challenges"). Good end-of-life care was facilitated through collaborative and network approaches to service provision, and effective communication with families. The implementation of 24/7 advice lines and the formalisation of joint-working arrangements were highlighted as a way to address the current challenges in the specialism. CONCLUSIONS: Findings demonstrate how informal and formal relationships between organisations and individuals, enabled early communication with families, and collaborative working with specialist services. Formalising these could increase knowledge and awareness of end of life care, improve staff confidence, and overall improve professionals' experiences of delivering care, and families' experiences of receiving it. There are considerable positives that come from collaborative working between different organisations and sectors, and care could be improved if these approaches are funded and formalised. There needs to be consistent funding for paediatric palliative care and there is a clear need for education and training to improve staff knowledge and confidence.

An exploration of the use of photobiomodulation for management of oral mucositis in children and young people undergoing cancer treatment in the UK.

PURPOSE: Oral mucositis affects up to 80% of children and young people (CYP) receiving chemotherapy. This can result in pain, reduced oral intake and, in severe cases, hospitalisation for parental nutrition and pain relief. Photobiomodulation is recommended by multiple bodies for mucositis management for those undergoing cancer treatments. The current use of photobiomodulation within the UK, and the barriers and facilitators to implementation is unknown. METHOD: An online mixed-methods survey was administered to representatives from the Children's Cancer and Leukaemia Group (CCLG) between October 2021 and March 2022. This explored: use of photobiomodulation, planned future use, barriers and facilitators to implementation and dental assessment. Quantitative data underwent descriptive statistics. Barriers and facilitators to the implementation of photobiomodulation were analysed using the Theoretical Domains Framework (TDF). RESULTS: All UK CCLG centres responded (n = 20, a response rate of 100%). Two units in Scotland were delivering photobiomodulation. A further four units were planning to implement a service. Most units, 65% (n = 13) utilised specialist Paediatric Dentistry services for dental assessment. In the TDF analysis, five domains were most frequently populated: knowledge, skills, environmental context and resources, social influences, and social/professional role and identity. CONCLUSION: Photobiomodulation was only available in Scotland in two children's cancer units. Lack of knowledge and skills, and insufficient environmental resources were identified as barriers. Collaboration with paediatric dental services was identified as a facilitator. The establishment of a national network of Paediatric Dentists and Oncologists would promote collaboration to standardise protocols and to address the identified barriers to wider implementation of photobiomodulation.

Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

COVID-19 and children with cancer: Parents' experiences, anxieties and support needs.

BACKGROUND: Children with cancer were designated as clinically extremely vulnerable if they were to contract SARS-CoV-2 due to immune suppression in the early phase of the COVID-19 pandemic. Our aim was to explore experiences, information and support needs, and decision making of parents with a child with cancer in response to this phase in the United Kingdom. METHODS: Parents of a child with cancer completed a survey at a time when the UK moved into a period of 'lockdown'. An online survey was developed by the research team to capture parents' experiences, information and support needs, and decision making, using closed statements and open text boxes. Descriptive quantitative analyses and qualitative thematic content analysis were undertaken. FINDINGS: One hundred seventy-one parents/caregivers completed the survey. Eighty-five percent were worried about the virus and they were vigilant about the virus (92%) or cancer symptoms (93.4%). For two-thirds (69.6%), hospital was no longer considered a safe place. Eight overarching themes were identified related to the virus: (a) risk of infection; (b) information, guidance and advice; (c) health care provision; (d) fears and anxieties; or related to lockdown/isolation: (e) psychological and social impact; (f) keeping safe under lockdown; (g) provisions and dependence; and (h) employment and income. CONCLUSIONS: This is the first study, to the best of our knowledge, to report experiences of parents of a child with cancer during the SARS-CoV-2/COVID-19 pandemic. The majority of parents were worried about SARS-CoV-2 and transmitting the virus to their child. Hospital was no longer perceived to be a safe place, and parents were worried about suboptimal cancer care. Parents described fear and anxiety and the psychological, social and economic impact of isolation.

Home-based care of low-risk febrile neutropenia in children-an implementation study in a tertiary paediatric hospital.

BACKGROUND: Home-based management of low-risk febrile neutropenia (FN) is safe, improves quality of life and reduces healthcare expenditure. A formal low-risk paediatric program has not been implemented in Australia. We aimed to describe the implementation process and evaluate the clinical impact. METHOD: This prospective study incorporated three phases: implementation, intervention and evaluation. A low-risk FN implementation toolkit was developed, including a care-pathway, patient information, home-based assessment and educational resources. The program had executive-level endorsement, a multidisciplinary committee and a nurse specialist. Children with cancer and low-risk FN were eligible to be transferred home with a nurse visiting daily after an overnight period of observation for intravenous antibiotics. Low-risk patients were identified using a validated decision rule, and suitability for home-based care was determined using disease, chemotherapy and patient-level criteria. Plan-Do-Study-Act methodology was used to evaluate clinical impact and safety. RESULTS: Over 18 months, 292 children with FN were screened: 132 (45%) were low-risk and 63 (22%) were transferred to home-based care. Compared with pre-implementation there was a significant reduction in in-hospital median LOS (4.0 to 1.5 days, p < 0.001) and 291 in-hospital bed days were saved. Eight (13%) patients needed readmission and there were no adverse outcomes. A key barrier was timely screening of all patients and program improvements, including utilising the electronic medical record for patient identification, are planned. CONCLUSION: This program significantly reduces in-hospital LOS for children with low-risk FN. Ongoing evaluation will inform sustainability, identify areas for improvement and support national scale-up of the program.

Reporting the whole story: Analysis of the 'out-of-scope' questions from the James Lind Alliance Teenage and Young Adult Cancer Priority Setting Partnership Survey.

OBJECTIVE: We conducted a UK-wide survey to identify the top 10 research questions for young people's cancer. We conducted secondary analysis of questions submitted, which were 'out-of-scope' of the original survey aim. We sought to disseminate these questions, to inform practice, policy and the development of potential interventions to support young people with cancer. DESIGN: James Lind Alliance Priority Setting Partnership. PARTICIPANTS: Young people aged 13-24 with a current/previous cancer diagnosis, their families/friends/partners and professionals who work with this population. METHODS: Eight hundred and fifty-five potential research questions were submitted, and 326 were classified as 'out-of-scope'. These questions, along with 49 'free-text' comments, were analysed using thematic analysis. RESULTS: The 375 out-of-scope questions and comments were submitted by: 68 young people, 81 family members/partners/friends and 42 professionals. Ten overarching themes were identified: diagnostic experience; communication; coordination of care; information needs and lack of information; service provision; long-term effects and aftercare support; family support; financial impact; end-of life care; and research methods and current research. CONCLUSIONS: The need to tailor services, information and communication is a striking thread evidenced across the 'out-of-scope' questions. Gaps in information highlight implications for practice in revisiting information needs throughout the cancer trajectory. We must advocate for specialist care for young people and promote the research priorities and these findings to funding bodies, charities, young people and health and social care policymakers, in order to generate an evidence base to inform effective interventions across the cancer trajectory and improve outcomes. PATIENT/PUBLIC CONTRIBUTIONS: Patients and carers were equal stakeholders throughout.

Guideline for Antibacterial Prophylaxis Administration in Pediatric Cancer and Hematopoietic Stem Cell Transplantation.

BACKGROUND: Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric patients with cancer and those undergoing HSCT. METHODS: An international and multidisciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate, and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature. RESULTS: The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia. CONCLUSIONS: We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis.

Interventions aiming to reduce time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN), a systematic review.

PURPOSE: Multiple interventions have been developed aiming to reduce time to antibiotics (TTA) in patients with fever and neutropenia (FN) following chemotherapy for cancer. We evaluated their effect to reduce TTA and their impact on important clinical outcomes in a systematic review. METHODS: The search covered seven databases. Biases and quality of studies were assessed with the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Interventions could be implemented in any setting and performed by any person included in the FN management. Absolute change of TTA was the primary outcome. Registration: PROSPERO (CRD42018092948). RESULTS: Six thousand two hundred ninety-six titles and abstracts were screened, 177 studies were retrieved and 30 studies were included. Risk of bias was moderate to serious in 28 studies and low in two studies. All but one study reported a reduction of TTA after the intervention. Various types of interventions were implemented; they most commonly aimed at professionals. Most of the studies made more than one single intervention. CONCLUSION: This review may help centers to identify their specific sources of delay and barriers to change and to define what intervention may be the best to apply. This review supports the assertion that TTA can be considered a measure of quality of care, emphasizes the importance of education and training, and describes the very different interventions which have effectively reduced TTA.

Association of time to antibiotics and clinical outcomes in patients with fever and neutropenia during chemotherapy for cancer: a systematic review.

PURPOSE: Prompt antibiotic therapy is standard of care for patients with fever and neutropenia (FN) during chemotherapy for cancer. We systematically reviewed the association between time to antibiotics (TTA) and clinical outcomes. METHODS: The search covered seven databases; confounding biases and study quality were assessed with the ROBINS-I tool. Safety (death, intensive care unit (ICU) admission, sepsis) and treatment adequacy (relapse of infection, persistence or recurrence of fever) were assessed as primary outcomes. RESULTS: Of 6296 articles identified, 13 observational studies were included. Findings regarding safety were inconsistent. Three studies controlling for triage bias showed a possible association between longer TTA and impaired safety. Meta-analysis for TTA ≤ 60 min versus > 60 min was feasible on four studies, with three studies each reporting on death (OR 0.78, 95%CI 0.16-3.69) and on ICU admission (OR 1.43, 95%CI 0.57-3.60). No study reported data on treatment adequacy. Triage bias, i.e. faster treatment of patients with worse clinical condition, was identified as a relevant confounding factor. CONCLUSION: There seems to be an association between longer TTA and impaired safety. More knowledge about TTA effects on safety are important to optimise treatment guidelines for FN. Controlling for triage and other biases is necessary to gain further evidence. TRIAL REGISTRATION: Registration: PROSPERO [http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018092948].

Specialist paediatric palliative care for children and young people with cancer: A mixed-methods systematic review.

BACKGROUND: Specialist paediatric palliative care services are promoted as an important component of palliative care provision, but there is uncertainty about their role for children with cancer. AIM: To examine the impact of specialist paediatric palliative care for children and young people with cancer and explore factors affecting access. DESIGN: A mixed-methods systematic review and narrative synthesis (PROSPERO Registration No. CRD42017064874). DATA SOURCES: Database (CINAHL, Cochrane Database of Systematic Reviews, Embase, MEDLINE, PsycINFO) searches (2000-2019) identified primary studies of any design exploring the impact of and/or factors affecting access to specialist paediatric palliative care. Study quality was assessed using The Mixed Methods Appraisal Tool. RESULTS: An evidence base of mainly low- and moderate-quality studies (n = 42) shows that accessing specialist paediatric palliative care is associated with less intensive care at the end of life, more advance care planning and fewer in-hospital deaths. Current evidence cannot tell us whether these services improve children's symptom burden or quality of life. Nine studies reporting provider or family views identified uncertainties about what specialist paediatric palliative care offers, concerns about involving a new team, association of palliative care with end of life and indecision about when to introduce palliative care as important barriers to access. There was evidence that children with haematological malignancies are less likely to access these services. CONCLUSION: Current evidence suggests that children and young people with cancer receiving specialist palliative care are cared for differently. However, little is understood about children's views, and research is needed to determine whether specialist input improves quality of life.

The utility of routine surveillance screening with magnetic resonance imaging to detect tumor recurrence/progression in children with high-grade central nervous system tumors: a systematic review.

BACKGROUND: Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in children with high-grade central nervous system (CNS) tumors, although no consensus has been reached regarding its effectiveness and whether earlier detection is associated with improved patient outcomes. This review aimed to evaluate this practice and any associated benefits and harms. METHODS: Systematic searches for relevant studies were undertaken in a number of databases, including MEDLINE and EMBASE, from 1985 to August 2018. Study selection and data extraction was undertaken independently by two reviewers. Due to heterogeneity between studies, no pooling of data was undertaken. Reporting followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: No comparative studies were identified. Three retrospective observational studies involving 306 patients were reviewed. All had high risk of bias by virtue of study design. Two studies reported outcomes by symptomatic status-both recurrence rates and overall survival for asymptomatic patients were comparable with those for clinically symptomatic patients. No quality-of-life outcomes were reported. CONCLUSION: There is a paucity of evidence to guide clinical practice as to the effectiveness of MRI surveillance in pediatric patients with high-grade CNS tumors. These studies do not clearly demonstrate benefit or harm for the practice. With more research needed, there is a role for researchers to build into future trials data collection on surveillance imaging to give more information for the assessment of imaging frequency and duration in asymptomatic patients. This is an important question not only to clinicians and patients and their families but also from a health service resource perspective.

Fifteen-minute consultation: A guide to managing a child with a new finding of neutropenia.

OBJECTIVE: To describe a structured approach for managing a child with a new finding of neutropenia. METHOD: Literature review and consensus practice of clinicians in our regional centre. CONCLUSION: Neutropenia may arise in a variety of situations from a well child with a physiological neutropenia to a sick infant with life-threatening infection. In most cases a thoughtful history and directed examination will help to identify the severity in order to determine an appropriate care pathway. SCENARIO: A 6-year-old boy presented earlier in the day to the acute assessment unit with lethargy and a sore throat. At handover time his blood results are phoned through and show that he is neutropenic.

Accuracy of cystatin C for the detection of abnormal renal function in children undergoing chemotherapy for malignancy: a systematic review using individual patient data.

PURPOSE: We conducted a systematic review and individual patient data (IPD) meta-analysis to examine the utility of cystatin C for evaluation of glomerular function in children with cancer. METHODS: Eligible studies evaluated the accuracy of cystatin C for detecting poor renal function in children undergoing chemotherapy. Study quality was assessed using QUADAS-2. Authors of four studies shared IPD. We calculated the correlation between log cystatin C and GFR stratified by study and measure of cystatin C. We dichotomized the reference standard at GFR 80 ml/min/1.73m2 and stratified cystatin C at 1 mg/l, to calculate sensitivity and specificity in each study and according to age group (0-4, 5-12, and ≥ 13 years). In sensitivity analyses, we investigated different GFR and cystatin C cut points. We used logistic regression to estimate the association of impaired renal function with log cystatin C and quantified diagnostic accuracy using the area under the ROC curve (AUC). RESULTS: Six studies, which used different test and reference standard thresholds, suggested that cystatin C has the potential to monitor renal function in children undergoing chemotherapy for malignancy. IPD data (504 samples, 209 children) showed that cystatin C has poor sensitivity (63%) and moderate specificity (89%), although use of a GFR cut point of < 60 ml/min/1.73m2 (data only available from two of the studies) estimated sensitivity to be 92% and specificity 81.3%. The AUC for the combined data set was 0.890 (95% CI 0.826, 0.951). Diagnostic accuracy appeared to decrease with age. CONCLUSIONS: Cystatin C has better diagnostic accuracy than creatinine as a test for glomerular dysfunction in young people undergoing treatment for cancer. Diagnostic accuracy is not sufficient for it to replace current reference standards for predicting clinically relevant impairments that may alter dosing of important nephrotoxic agents.

Guidelines for the Prophylaxis of Pneumocystis jirovecii Pneumonia (PJP) in Children With Solid Tumors.

Although it is well-established that children undergoing allogeneic stem cell transplants and treatment for leukemia should be offered prophylaxis against Pneumocystis jirovecii pneumonia, the risk for children with solid malignancies is less certain. This guideline has been developed with the aim of standardizing practice and optimizing the benefit versus risk of prophylactic medication in this group of patients. P. jirovecii pneumonia has a high mortality rate even with prompt antimicrobial treatment. Since prophylaxis with co-trimoxazole is safe, effective, and inexpensive, we suggest that all children with malignancies undergoing immunosuppressive therapy are offered prophylaxis unless there are clear contraindications.

Prospective cohort study of procalcitonin levels in children with cancer presenting with febrile neutropenia.

BACKGROUND: Febrile neutropenia (FNP) causes significant morbidity and mortality in children undergoing treatment for cancer. The development of clinical decision rules to help stratify risks in paediatric FNP patients and the use of inflammatory biomarkers to identify high risk patients is an area of recent research. This study aimed to assess if procalcitonin (PCT) levels could be used to help diagnose or exclude severe infection in children with cancer who present with febrile neutropenia, both as a single measurement and in addition to previously developed clinical decision rules. METHODS: This prospective cohort study of a diagnostic test included patients between birth and 18 years old admitted with febrile neutropenia to the Paediatric Oncology and Haematology Ward in Leeds between 1st October 2012 and 30th September 2013. Each admission with FNP was treated as a separate episode. Blood was taken for a procalcitonin level at admission with routine investigations. 'R' was used for statistical analysis. Likelihood ratios were calculated and multivariable logistic regression. RESULTS: Forty-eight episodes from 27 patients were included. PCT >2 ng/dL was strongly associated with increased risk of severe infection (likelihood ratio of 26 [95% CI 3.5, 190]). The data suggests that the clinical decision rules are largely ineffective at risk stratification, frequently over-stating the risk of individual episodes. High procalcitonin levels on admission are correlated with a greatly increased risk of severe infection. CONCLUSIONS: This study does not show a definitive benefit in using PCT in FNP though it supports further research on its use. The benefit of novel biomarkers has not been proven and before introducing new tests for patients it is important their benefit above existing features is proven, particularly due to the increasing importance of health economics.

Galactomannan, ß-D-Glucan, and Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

We systematically reviewed and analyzed the available data for galactomannan (GM), ß-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive fungal disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT.