Childhood Cancer Incidence and Survival in South Australia and the Northern Territory, 1990-2017, with Emphasis on Indigenous Peoples.

BACKGROUND & AIMS: Reports of a rise in childhood cancer incidence in Australia and globally prompted the investigation of cancer incidence and survival in South Australia (SA) and the Northern Territory (NT) over a 28-year period, with emphasis on Indigenous peoples. METHODS: This cross-sectional analysis of two prospective longitudinal databases, the SA and NT Cancer Registries (1990-2017), included all reported cases of childhood cancers. Poisson regression provided estimates of incidence rate ratios and survival was modelled using Cox proportional hazard models for children aged <5 and ≥5 years. RESULTS: A total of 895 patients across SA (N = 753) and the NT (N = 142) were ascertained. Overall and in the NT, childhood cancer incidence was higher in males compared with females (IRR 1.19 [1.04-1.35] and 1.43 [1.02-2.01], respectively). Lymphocytic leukemia was the most reported cancer type across all locations. With reference to the 1990-1999 era (181.67/100,000), cancer incidence remained unchanged across subsequent eras in the combined cohort (SA and NT) (2000-2009: 190.55/100,000; 1.06 [0.91-1.25]; 2010-2017: 210.00/100,000; 1.15 [0.98-1.35]); similar outcomes were reflected in SA and NT cohorts. Cancer incidence amongst non-Indigenous children significantly decreased from the 1990-1999 era (278.32/100,000) to the 2000-2009 era (162.92/100,000; 0.58 [0.35-0.97]). Amongst 39 Indigenous children in the NT, incidence rates remained unchanged across eras (p > 0.05). With reference to the 1990-1999 era, overall survival improved in subsequent eras in SA (2000-2009: HR 0.53 [0.38-0.73]; 2010-2017: 0.44 [0.28-0.68]); however, remained unchanged in the NT (2000-2009: 0.78 [0.40-1.51]; 2010-2017: 0.50 [0.24-1.05]). In the NT, overall survival of Indigenous patients was significantly lower compared with the non-Indigenous cohort (3.42 [1.92-6.10]). While the survival of Indigenous children with cancer significantly improved in the last two eras (p < 0.05), compared to the 1990-1999 era, no change was noted amongst non-Indigenous children in the NT (p > 0.05). CONCLUSIONS: The incidence of childhood cancers has remained unchanged over 28-years in SA and the NT. Encouragingly, improved survival rates over time were observed in SA and amongst Indigenous children of the NT. Nevertheless, survival rates in Indigenous children remain lower than non-Indigenous children.

Case Report: Rare IKZF1 Gene Fusions Identified in Neonate with Congenital KMT2A-Rearranged Acute Lymphoblastic Leukemia.

Chromosomal rearrangements involving the KMT2A gene occur frequently in acute lymphoblastic leukaemia (ALL). KMT2A-rearranged ALL (KMT2Ar ALL) has poor long-term survival rates and is the most common ALL subtype in infants less than 1 year of age. KMT2Ar ALL frequently occurs with additional chromosomal abnormalities including disruption of the IKZF1 gene, usually by exon deletion. Typically, KMT2Ar ALL in infants is accompanied by a limited number of cooperative le-sions. Here we report a case of aggressive infant KMT2Ar ALL harbouring additional rare IKZF1 gene fusions. Comprehensive genomic and transcriptomic analyses were performed on sequential samples. This report highlights the genomic complexity of this particular disease and describes the novel gene fusions IKZF1::TUT1 and KDM2A::IKZF1.

COVID-19 vaccination in children and adolescents aged 5 years and older undergoing treatment for cancer and non-malignant haematological conditions: Australian and New Zealand Children's Haematology/Oncology Group consensus statement.

INTRODUCTION: The Australian Technical Advisory Group on Immunisation and New Zealand Ministry of Health recommend all children aged ≥ 5 years receive either of the two mRNA COVID-19 vaccines: Comirnaty (Pfizer), available in both Australia and New Zealand, or Spikevax (Moderna), available in Australia only. Both vaccines are efficacious and safe in the general population, including children. Children and adolescents undergoing treatment for cancer and immunosuppressive therapy for non-malignant haematological conditions are particularly vulnerable, with an increased risk of severe or fatal COVID-19. There remains a paucity of data regarding the immune response to COVID-19 vaccines in immunosuppressed paediatric populations, with data suggestive of reduced immunogenicity of the vaccine in immunocompromised adults. RECOMMENDATIONS: Considering the safety profile of mRNA COVID-19 vaccines and the increased risk of severe COVID-19 in immunocompromised children and adolescents, COVID-19 vaccination is strongly recommended for this at-risk population. We provide a number of recommendations regarding COVID-19 vaccination in this population where immunosuppressive, chemotherapeutic and/or targeted biological agents are used. These include the timing of vaccination in patients undergoing active treatment, management of specific situations where vaccination is contraindicated or recommended under special precautions, and additional vaccination recommendations for severely immunocompromised patients. Finally, we stress the importance of upcoming clinical trials to identify the safest and most efficacious vaccination regimen for this population. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This consensus statement provides recommendations for COVID-19 vaccination in children and adolescents aged ≥ 5 years with cancer and immunocompromising non-malignant haematological conditions, based on evidence, national and international guidelines and expert opinion. ENDORSED BY: The Australian and New Zealand Children's Haematology/Oncology Group.