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Symptomatic methotrexate-related central neurotoxicity (MTX neurotoxicity) is a severe toxicity experienced during acute lymphoblastic leukemia (ALL) therapy with potential long-term neurologic complications. Risk factors and long-term outcomes require further study.

Outcomes for infants diagnosed under 1 year of age with KMT2A-rearranged acute lymphoblastic leukemia (ALL) have remained stagnant over the past 20 years. Successive treatment protocols have previously focused on intensification of conventional chemotherapy, but increased treatment-related toxicity and chemoresistance have led to a plateau in survival.

Children receiving treatment for acute myeloid leukemia (AML) are at high risk of invasive fungal disease (IFD). Evidence from pediatric studies support the efficacy of antifungal prophylaxis in reducing the burden of IFD in children receiving therapy for AML, yet existing antifungal agents have specific limitations and comparative data to inform the optimal prophylactic approach are lacking.

Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy and remains one of the most common causes of cancer-related death in children and adolescents. Five-year overall survival rates now exceed 90% with current multidrug chemotherapeutic regimens.

B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by diverse genomic alterations, the most frequent being gene fusions detected via transcriptomic analysis (mRNA-seq). Due to its hypervariable nature, gene fusions involving the Immunoglobulin Heavy Chain (IGH) locus can be difficult to detect with standard gene fusion calling algorithms and significant computational resources and analysis times are required. We aimed to optimize a gene fusion calling workflow to achieve best-case sensitivity for IGH gene fusion detection.

PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL and gather insight into the clearance and dosing of this population.

T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10-20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing.

Rishi S. Kotecha MB ChB (Hons) MRCPCH FRACP PhD Co-Head, Leukaemia Translational Research rishi.kotecha@health.wa.gov.au Co-Head, Leukaemia

Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children's Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy.

Rearrangements of the Mixed Lineage Leukemia (MLL/KMT2A) gene are present in approximately 10% of acute leukemias and characteristically define disease with poor outcome.