Incidence and outcome of osteonecrosis and use of prophylactic zoledronic acid for chemotherapy related osteonecrosis in children and adolescents with acute lymphoblastic leukaemia and lymphoma.

Background: Survival of ALL/LL is > 90% in children and adolescents. Treatment related long term toxicity is a significant issue. ON is a debilitating complication and decreases quality of life of the survivors. There is no preventive therapy for ON. Aims: To describe incidence and outcome of ON in patients with ALL/LL. To describe use of ZA in treatment of ON. To describe safety and feasibility of prophylactic ZA in patients with ALL/LL. Methods: A descriptive analysis of incidence and outcome of ON in a group of 251 children undergoing chemotherapy and 72 patients undergoing HSCT for ALL/LL was conducted. A descriptive analysis of use of ZA for treatment of chemotherapy induced ON was performed. A pilot study was conducted to determine safety and feasibility of using prophylactic doses of ZA in patients undergoing treatment for ALL/LL. Results: Seven percent of children undergoing chemotherapy for ALL/LL and 12.5%of patients undergoing HSCT developed ON. Age >10 years was the most important risk factor. When ZA was used for treatment of ON, many patients reported improvement in pain but most patients with hip joint involvement progressed needing arthroplasty. Prophylactic administration of ZA was safe and feasible with chemotherapy for ALL/LL, asymptomatic hypocalcemia being the most common side-effect. Conclusion: ON is significant complication of treatment for ALL/LL and most patients develop progressive joint destruction despite treatment with ZA. This is the first study to have prophylactic intervention for prevention of symptomatic ON in patients with ALL/LL without changing planned chemotherapy. Safety and feasibility of this intervention undertaken concurrently with chemotherapy is documented, a larger study is needed to comment on efficacy of this approach

Late effects and treatment related morbidity associated with treatment of neuroblastoma patients in a tertiary paediatric centre

Abstract Background Survival of neuroblastoma patients has improved over recent decades, but chronic health issues and treatment related late effects cause significant morbidity in survivors. Aims We aimed to describe late effects and long‐term toxicity in neuroblastoma patients treated at a tertiary, paediatric institution in Australia. Methods & Results Patients with neuroblastoma treated primarily at The Children's hospital at Westmead were eligible for inclusion. Retrospective analysis of 65 (45 with high‐risk and 20 with non‐high‐risk disease) neuroblastoma patients were performed via medical record review. Approximately 60% of patients were >5 years from diagnosis and termed the “full effects cohort” who had a range of medical and psychosocial late effects analysed through descriptive means. The remaining 26 patients who had not yet reached 5 years post treatment had audiometry analysis only. Of the 65 patients, 72% were alive at last follow‐up. The median length of follow‐up was 7 years from diagnosis amongst survivors. Therapy was according to contemporary protocols for neuroblastoma and ranged from standard cytotoxic therapies to intensive multimodal regimens and/or experimental therapy depending on risk group/relapse status. Of the 39 full effects cohort, 85% suffered from at least one late effect. Late effects were common in the endocrine, dental and audiometry domains with 38%, 49% and 72% of patients affected in these areas, respectively. Neuro‐cognitive domains were also notably affected with 46% of patients suffering a deficit. Two thirds of survivors were disease free at last follow‐up. Conclusion Survivors of high‐risk neuroblastoma suffer from a range of chronic illnesses, which lead to morbidity and affect quality of life of survivors

Diagnostic Yield of Initial and Consecutive Blood Cultures in Children With Cancer and Febrile Neutropenia

BACKGROUND: The timing and necessity of repeated blood cultures (BCs) in children with cancer and febrile neutropenia (FN) are unknown. We evaluated the diagnostic yield of BCs collected pre- and post-empiric FN antibiotics. METHODS: Data collected prospectively from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study were used. Diagnostic yield was calculated as the number of FN episodes with a true bloodstream infection (BSI) detected divided by the number of FN episodes that had a BC taken. RESULTS: A BSI was identified in 13% of 858 FN episodes. The diagnostic yield of pre-antibiotic BCs was higher than of post-antibiotic cultures (12.3% vs 4.4%, P < .001). Two-thirds of the post-antibiotic BSIs were associated with a new episode of fever or clinical instability, and only 2 new BSIs were identified after 48 hours of empiric antibiotics and persistent fever. A contaminated BC was identified more frequently in post-antibiotic cultures. CONCLUSIONS: In the absence of new fever or clinical instability, BCs beyond 48 hours of persistent fever have limited yield. Opportunity exists to optimize BC collection in this population and reduce the burden of unnecessary tests on patients, healthcare workers, and hospitals

Protocol for a comprehensive prospective cohort study of trio-based whole-genome sequencing for underlying cancer predisposition in paediatric and adolescent patients newly diagnosed with cancer: the PREDICT study

Introduction Identifying an underlying germline cancer predisposition (CP) in a child with cancer has potentially significant implications for both the child and biological relatives. Cohort studies indicate that 10%–15% of paediatric cancer patients carry germline pathogenic or likely pathogenic variants in cancer predisposition genes, but many of these patients do not meet current clinical criteria for genetic testing. This suggests broad tumour agnostic germline testing may benefit paediatric cancer patients. However, the utility and psychosocial impact of this approach remain unknown. We hypothesise that an approach involving trio whole-genome germline sequencing (trio WGS) will identify children and families with an underlying CP in a timely fashion, that the trio design will streamline cancer risk counselling to at-risk relatives if CP was inherited, and that trio testing will not have a negative psychosocial impact on families.Method and analysis To test this, we present the Cancer PREDisposition In Childhood by Trio sequencing study (PREDICT). This study will assess the clinical utility of trio WGS to identify CP in unselected patients with cancer 21 years or younger in New South Wales, Australia. PREDICT will perform analysis of biological parents to determine heritability and will examine the psychosocial impact of this trio sequencing approach. PREDICT also includes a broad genomics research programme to identify new candidate genes associated with childhood cancer risk.Ethics and dissemination By evaluating the feasibility, utility and psychosocial impact of trio WGS to identify CP in paediatric cancer, PREDICT will inform how such comprehensive testing can be incorporated into a standard of care at diagnosis for all childhood cancer patients.Trial registration number NCT04903782